{"query": "How much impact do masks have on preventing the spread of the COVID-19?", "hits": [{"content": "Title: Impact of self-imposed prevention measures and short-term government intervention on mitigating and delaying a COVID-19 epidemic Content: Background: With new cases of COVID-19 surging around the world, many countries have to prepare for moving beyond the containment phase. Prediction of the effectiveness of non-case-based interventions for mitigating, delaying or preventing the epidemic is urgent, especially for countries affected by the ongoing seasonal influenza activity. Methods: We developed a transmission model to evaluate the impact of self-imposed prevention measures (handwashing, mask-wearing, and social distancing) due to the spread of COVID-19 awareness and of short-term government-imposed social distancing on the peak number of diagnoses, attack rate and time until the peak number of diagnoses. Findings: For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate, diminish and postpone the peak number of diagnoses. A large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government interventions can only delay the peak (by at most 7 months for a 3-month intervention). Interpretation: Handwashing, mask-wearing and social distancing as a reaction to information dissemination about COVID-19 can be effective strategies to mitigate and delay the epidemic. We stress the importance of rapidly spreading awareness on the use of these self-imposed prevention measures in the population. Early-initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. Keywords: SARS-CoV-2, COVID-19, mathematical model, prevention measures, mitigation, epidemic control, disease awareness, social distancing, handwashing, mask-wearing", "qid": 44, "docid": "xfjexm5b", "rank": 1, "score": 12.713800430297852}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17--45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34--58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24--65% (and peak deaths 15--69%), compared to 2--9% mortality reduction in New York (peak death reduction 9--18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 44, "docid": "28utunid", "rank": 2, "score": 11.653200149536133}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17\u201345% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34\u201358%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24\u201365% (and peak deaths 15\u201369%), compared to 2\u20139% mortality reduction in New York (peak death reduction 9\u201318%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 44, "docid": "qi1henyy", "rank": 3, "score": 11.653199195861816}, {"content": "Title: Analysis on Novel Coronavirus (COVID-19) Using Machine Learning Methods Content: In this paper, we are working on a pandemic of novel coronavirus (COVID-19). COVID-19 is an infectious disease, it creates severe damage in the lungs. COVID-19 causes illness in humans and has killed many people in the entire world. However, this virus is reported as a pandemic by the World Health Organization (WHO) and all countries are trying to control and lockdown all places. The main objective of this work is to solve the five different tasks such as I) Predicting the spread of coronavirus across regions. II) Analyzing the growth rates and the types of mitigation across countries. III) Predicting how the epidemic will end. IV) Analyzing the transmission rate of the virus. V) Correlating the coronavirus and weather conditions. The advantage of doing these tasks to minimize the virus spread by various mitigation, how well the mitigations are working, how many cases have been prevented by this mitigations, an idea about the number of patients that will recover from the infection with old medication, understand how much time will it take to for this pandemic to end, we will be able to understand and analyze how fast or slow the virus is spreading among regions and the infected patient to reduce the spread based clear understanding of the correlation between the spread and weather conditions. In this paper, we propose a novel Support Vector Regression method to analysis five different tasks related to novel coronavirus. In this work, instead of simple regression line we use the supported vectors also to get better classification accuracy. Our approach is evaluated and compared with other well-known regression models on standard available datasets. The promising results demonstrate its superiority in both efficiency and accuracy.", "qid": 44, "docid": "qp77vl6h", "rank": 4, "score": 11.350500106811523}, {"content": "Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "qid": 44, "docid": "ugkxxaeb", "rank": 5, "score": 11.312800407409668}, {"content": "Title: Preparedness and Preventive Behaviors for a Pandemic Disaster Caused by COVID-19 in Serbia Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The disease was first detected in Wuhan, the capital of China\u2019s Hubei province, in December 2019 and has since spread globally, especially to Europe and North America, resulting in the ongoing global coronavirus pandemic disaster of 2019\u20132020. Although most cases have mild symptoms, there is some progression to viral pneumonia and multi-organ failure and death. More than 4.6 million cases have been registered across 216 countries and territories as of 19 April 2020, resulting in more than 311,000 deaths. Risk to communities with continued widespread disease transmission depends on characteristics of the virus, including how well it spreads between people; the severity of resulting illness; and the medical or other measures available to control the impact of the virus (for example, vaccines or medications that can treat the illness) and the relative success of these. In the absence of vaccines or medications, non-pharmaceutical interventions were the most important response strategy based on community interventions such as person-to-person distancing, mask-wearing, isolation and good personal hygiene (hand-washing)\u2014all of which have been demonstrated can reduce the impact of this seemingly unstoppable globally spreading natural disaster. This paper presents the results of quantitative research regarding the level of citizen preparedness for disasters caused by coronavirus disease (COVID-19) in Serbia. The survey was conducted using a questionnaire that was requested and then collected online among 975 respondents during disaster in April 2020. The questionnaire examined citizens\u2019 basic socio-economic and demographic characteristics, their knowledge, preparedness, risk perception and preventive measures taken individually and as a community to prevent the death and widespread transmission of novel coronavirus disease 2019 in the Republic of Serbia. Based on the findings that there are major differences in the public\u2019s perception of risks posed by communicable disease threats such as presented by COVID-19, emergency management agencies should use these differences to develop targeted strategies to enhance community and national preparedness by promoting behavioral change and improving risk management decision-making.", "qid": 44, "docid": "4cmeglm3", "rank": 6, "score": 10.799099922180176}, {"content": "Title: Preparedness and Preventive Behaviors for a Pandemic Disaster Caused by COVID-19 in Serbia Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The disease was first detected in Wuhan, the capital of China's Hubei province, in December 2019 and has since spread globally, especially to Europe and North America, resulting in the ongoing global coronavirus pandemic disaster of 2019-2020. Although most cases have mild symptoms, there is some progression to viral pneumonia and multi-organ failure and death. More than 4.6 million cases have been registered across 216 countries and territories as of 19 April 2020, resulting in more than 311,000 deaths. Risk to communities with continued widespread disease transmission depends on characteristics of the virus, including how well it spreads between people; the severity of resulting illness; and the medical or other measures available to control the impact of the virus (for example, vaccines or medications that can treat the illness) and the relative success of these. In the absence of vaccines or medications, non-pharmaceutical interventions were the most important response strategy based on community interventions such as person-to-person distancing, mask-wearing, isolation and good personal hygiene (hand-washing)-all of which have been demonstrated can reduce the impact of this seemingly unstoppable globally spreading natural disaster. This paper presents the results of quantitative research regarding the level of citizen preparedness for disasters caused by coronavirus disease (COVID-19) in Serbia. The survey was conducted using a questionnaire that was requested and then collected online among 975 respondents during disaster in April 2020. The questionnaire examined citizens' basic socio-economic and demographic characteristics, their knowledge, preparedness, risk perception and preventive measures taken individually and as a community to prevent the death and widespread transmission of novel coronavirus disease 2019 in the Republic of Serbia. Based on the findings that there are major differences in the public's perception of risks posed by communicable disease threats such as presented by COVID-19, emergency management agencies should use these differences to develop targeted strategies to enhance community and national preparedness by promoting behavioral change and improving risk management decision-making.", "qid": 44, "docid": "pklvvgd3", "rank": 7, "score": 10.79909896850586}, {"content": "Title: Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants Content: COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.", "qid": 44, "docid": "ej76fsxa", "rank": 8, "score": 10.756099700927734}, {"content": "Title: Forecasting the novel coronavirus COVID-19 Content: What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19.", "qid": 44, "docid": "d8eqifvv", "rank": 9, "score": 10.509400367736816}, {"content": "Title: Universal Masking is Urgent in the COVID-19 Pandemic: SEIR and Agent Based Models, Empirical Validation, Policy Recommendations Content: We present two models for the COVID-19 pandemic predicting the impact of universal face mask wearing upon the spread of the SARS-CoV-2 virus--one employing a stochastic dynamic network based compartmental SEIR (susceptible-exposed-infectious-recovered) approach, and the other employing individual ABM (agent-based modelling) Monte Carlo simulation--indicating (1) significant impact under (near) universal masking when at least 80% of a population is wearing masks, versus minimal impact when only 50% or less of the population is wearing masks, and (2) significant impact when universal masking is adopted early, by Day 50 of a regional outbreak, versus minimal impact when universal masking is adopted late. These effects hold even at the lower filtering rates of homemade masks. To validate these theoretical models, we compare their predictions against a new empirical data set we have collected that includes whether regions have universal masking cultures or policies, their daily case growth rates, and their percentage reduction from peak daily case growth rates. Results show a near perfect correlation between early universal masking and successful suppression of daily case growth rates and/or reduction from peak daily case growth rates, as predicted by our theoretical simulations. Our theoretical and empirical results argue for urgent implementation of universal masking. As governments plan how to exit societal lockdowns, it is emerging as a key NPI; a\"mouth-and-nose lockdown\"is far more sustainable than a\"full body lockdown\", on economic, social, and mental health axes. An interactive visualization of the ABM simulation is at http://dek.ai/masks4all. We recommend immediate mask wearing recommendations, official guidelines for correct use, and awareness campaigns to shift masking mindsets away from pure self-protection, towards aspirational goals of responsibly protecting one's community.", "qid": 44, "docid": "m5udub60", "rank": 10, "score": 10.48840045928955}, {"content": "Title: Children and adolescents in the CoVid-19 pandemic: Schools and daycare centers are to be opened again without restrictions. The protection of teachers, educators, carers and parents and the general hygiene rules do not conflict with this Content: In the opinion of the medical societies of hygiene and pediatrics undersigning the present statement, the analyses published to date regarding transmission of SARS-CoV-2 and the course of CoVid-19 show that children play a much less significant role in the spread of the virus than do adults. According to the findings available to date, not only do children and adolescents less frequently fall ill with CoVid-19, they also generally become less severely ill than do adults. The vast majority of infections in children and adolescents are asymptomatic or oligosymptomatic. Even the first analyses from China demonstrated that children and adolescents play a subordinate role in the transmission of the virus \u2013 not only to other children and adolescents, but also to adults. Taking into account regional infection rates and available resources, daycare centers, kindergartens and elementary schools promptly should be reopened. For children, this should be possible without excessive restrictions, such as clustering into very small groups, implementation of barrier precautions, maintaining appropriate distance from others or wearing masks. A factor more decisive than individual group size is the issue of sustaining the constancy of respective group members and the avoidance of intermixing. Children can be taught basic rules of hygiene such as handwashing and careful hygiene behavior when coming into contact with others during mealtimes and/or when using sanitary facilities. Independent of the prevention measures implemented for children and adolescents, the protection of teachers, educators and caregivers is crucial, (e.g., the maintenance of appropriate distance from others, use of medical masks, situation-dependent hand disinfection, when necessary, supported by regular pool testing). Children over the age of 10 and adolescents up to school graduation age are more capable of actively understanding and conforming to specific hygiene rules. For this group, maintaining appropriate distance from others (1.5 meters), wearing a mouth-and-nose protection (whenever they are not sitting in their assigned classroom seats) and consistent education regarding the basic rules of infection prevention may provide increased options for normalizing teaching activities. Children and adolescents suspected of infection with SARS-CoV-2 should be tested immediately in order to either confirm or rule out such an infection. Evidence of individual infections in children or students must not automatically lead to the closure of the entire daycare center or school. A detailed analysis of the chain of infection is a prerequisite for a balanced approach to infection control. The opening of schools and children\u2019s facilities should be accompanied by specifically structured, model surveillance studies that further clarify outstanding questions about infectious disease events and hygiene control. These prospective, concomitant examinations will be essential for the purpose of evaluating and verifying the effectiveness of the required hygiene measures.", "qid": 44, "docid": "zwb1mn7c", "rank": 11, "score": 10.458800315856934}, {"content": "Title: Does Collective Interest or Self-Interest Motivate Mask Usage as a Preventive Measure Against COVID-19? Content: The revised guidance on masks from public health officials has been one of the most significant COVID-19 policy reversals to date. Statements made at the outset of the pandemic, including those from the World Health Organization (WHO), the United States Surgeon General, and the Chief Public Health Officer of Canada, all actively discouraged asymptomatic members of the general public from wearing masks. However, on April 3, 2020, the United States Center for Disease Control and Prevention (CDC) issued new recommendations that called for nonmedical masks, such as cloth face coverings, to be worn in public settings where other social distancing measures are difficult to maintain (Adams, 2020). Canadian public health officials quickly followed with their own guidance for wearing nonmedical masks or face coverings when out in public; however, they have stressed that doing so is optional for asymptomatic persons and should be seen as a complement to existing precautionary measures such as physical distancing and hand hygiene, particularly in cases where physical distancing may not be feasible (Public Health Agency of Canada, 2020). Emphasis was placed on nonmedical masks serving not to protect the wearer, but rather others who come within close proximity of the wearer. Echoing her public statements on the matter, Canada's chief public health officer Tweeted that \u201c[w]earing a NON-MEDICAL mask in public settings has not been proven to add any protection TO the person wearing it, but it can be an additional way to prevent spread FROM an infected person to others\u201d (Tam, 2020).", "qid": 44, "docid": "pynqwj5t", "rank": 12, "score": 10.372599601745605}, {"content": "Title: Online National Health Agency Mask Guidance for the Public in Light of COVID-19: Content Analysis Content: BACKGROUND: The rapid global spread of the coronavirus disease (COVID-19) has compelled national governments to issue guidance on the use of face masks for members of the general public. To date, no work has assessed how this guidance differs across governments. OBJECTIVE: This study seeks to contribute to a rational and consistent global response to infectious disease by determining how guidelines differ across nations and regions. METHODS: A content analysis of health agency mask guidelines on agency websites was performed in late March 2020 among 25 countries and regions with large numbers of COVID-19 cases. Countries and regions were assigned across the coding team by language proficiency, with Google Translate used as needed. When available, both the original and English language version of guidance were reviewed. RESULTS: All examined countries and regions had some form of guidance online, although detail and clarity differed. Although 9 countries and regions recommended surgical, medical, or unspecified masks in public and poorly ventilated places, 16 recommended against people wearing masks in public. There were 2 countries that explicitly recommended against fabric masks. In addition, 12 failed to outline the minimum basic World Health Organization guidance for masks. CONCLUSIONS: Online guidelines for face mask use to prevent COVID-19 in the general public are currently inconsistent across nations and regions, and have been changing often. Efforts to create greater standardization and clarity should be explored in light of the status of COVID-19 as a global pandemic.", "qid": 44, "docid": "d53qyrew", "rank": 13, "score": 10.370400428771973}, {"content": "Title: The Impact of COVID-19 on Medical Education Content: In the wake of the novel coronavirus (COVID-19) pandemic, it is abundantly clear to all the necessity of studying the pathology and widespread health consequences associated with the virus. However, what is much less clear is the impact of COVID-19 on medical education. Already, faculty and medical students are grappling with the changes that have been made and attempting to consolidate these with their plan of career development. Changes that may seem relatively minor in comparison to the global pandemic have the potential to be drastic turning points in the career progression of many. As not much is known regarding the long-lasting impact of COVID-19 on medical education, it is therefore also necessary to record and study the full impact of the changes being made. The path to entering a successful residency has been predictable for the last few years - do well on Step 1, give conference presentations, go the extra mile in clerkships and shadowing opportunities, and have meaningful non-academic extracurricular activities - all of which designed to best demonstrate a student's knowledge, persistence, collaborative spirit, and dedication to medicine. This trajectory has been changed with COVID-19 disrupting routines in hospitals, medical schools and beyond. The replacement of in-person classes with online equivalents is an obvious necessity at this time but creates a loss of collaborative experiences that has the potential to be a significant detriment to education. Likewise, the cancellation of clerkships, which are necessary for both skill acquisition as well as for relationship building, is a serious issue which students and medical schools must now resolve. Many medical students have also lost the opportunity for personal development through conference presentations. These presentations play a large role in distinguishing applicants during the residency application process, and therefore these lost opportunities have the potential to be a serious detriment to medical students\u2019 career trajectory. While implementing technology to help resolve these issues is a unique way to help students to develop these skills, it is now necessary for medical students to demonstrate the same set of skills which they would have previously in a completely new and innovative manner. Persistence and adaptability during this time of challenge are attributes that medical students can demonstrate more readily. While every student has a personal story of how COVID-19 has impacted their education, there is no question that the impacts of COVID-19 will be felt on an extensive level. The panic in the community is palpable, and many are confused by how to proceed in the wake of COVID-19. This is no different for medical students and faculty and the questions that arise regarding medical education and their future careers.", "qid": 44, "docid": "i6khpntc", "rank": 14, "score": 10.33329963684082}, {"content": "Title: How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19)/ \u4e2d\u534e\u5b9e\u9a8c\u773c\u79d1\u6742\u5fd7 Content: The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community. The International Committee on Viral Classification named the virus &quot;Severe Acute Respiratory Syndrome Coronavirus 2&quot; (SARS-CoV-2), and the WHO named the pneumonia it causes &quot;Coronavirus Disease 2019&quot; (COVID-19). At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries. About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments. COVID-19 has infected an even greater number of heath care workers. Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures. Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments. This risk will only increase as the number of infected patients continues to increase. When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced. To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists. These measures include 1) wearing an efficient mask (an N95 mask); 2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient\u2019s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; 5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; 6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; 7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time; 8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak; and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.", "qid": 44, "docid": "gbvyuem5", "rank": 15, "score": 10.2475004196167}, {"content": "Title: How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19) Content: The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community The International Committee on Viral Classification named the virus &amp;quot;Severe Acute Respiratory Syndrome Coronavirus 2&amp;quot;(SARS-CoV-2), and the WHO named the pneumonia it causes &amp;quot;Coronavirus Disease 2019&amp;quot;(COVID-19) At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments COVID-19 has infected an even greater number of heath care workers Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments This risk will only increase as the number of infected patients continues to increase When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists These measures include 1) wearing an efficient mask (an N95 mask);2) always performing hand hygiene before and after examining a patient;(3) wearing sterile gloves when entering a patient\u2019s room and touching a patient;(4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid;5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined;6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface;7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time;8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak;and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations", "qid": 44, "docid": "q76jxc3p", "rank": 16, "score": 10.247499465942383}, {"content": "Title: How ophthalmologists should understand and respond to the current epidemic of novel coronavirus pneumonia/ \u773c\u79d1\u533b\u751f\u548c\u7814\u7a76\u4eba\u5458\u5982\u4f55\u7406\u89e3\u548c\u5e94\u5bf9\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u7684\u6d41\u884c Content: The new coronavirus pneumonia (COVID-19)that caused by 2019 new coronavirus (2019-nCoV) and first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community.The International Committee on Viral Classification named the virus \"Severe Acute Respiratory Syndrome Coronavirus 2\" (SARS-CoV-2), and the WHO named the pneumonia it causesCOVID-19\". At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries.About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments.COVID-19 has infected an even greater number of heath care workers.Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures.Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments.This risk will only increase as the number of infected patients continues to increase.When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced.To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists.These measures include (1) wearing an efficient mask (an N95 mask); (2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient\u2019s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; (5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; (6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; (7) performing the relevant screening for COVID-19 for regular patients who have conjunctivitis and respiratory symptoms at the same time; (8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor 2019-CoV screening to the medical standard of the eye bank during the outbreak; (9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.", "qid": 44, "docid": "aezp1isw", "rank": 17, "score": 10.207799911499023}, {"content": "Title: The relative power of individual distancing efforts and public policies to curb the COVID-19 epidemics Content: Lockdown curbs the COVID-19 epidemics but at huge costs. Public debates question its impact ompared with reliance on individual responsibility. We aim at understanding how rationally chosen self-protective behavior impacts the spread of the epidemics. We want to, first, assess the value of lockdown compared to a counterfactual that incorporates self-protection efforts under unknown disease prevalence; and second, assess how individual behavior modify the epidemic dynamics when mandatory policies are relaxed. We couple an SLIAR model, that includes asymptomatic transmission, with utility maximization: Individuals trade off economic and wellbeing costs from physical distancing with a lower infection risk. Effort depends on risk aversion, perceptions, and the value of contacts. In a Nash equilibrium, individual uncoordinated efforts yield average contact intensity, which drives epidemic transmission. Equilibrium effort differs markedly from constant, stochastic or proportional contacts reduction. It adjusts to reported cases in a way that creates a slightly decreasing plateau in epidemic prevalence. Calibration on French data shows that the number of deaths with no lockdown but equilibrium efforts is only 1/6 to 1/10 of the number predicted with business-as-usual. However, lockdown saves at least 50% more lives than individual efforts alone. Prolonged weaker restrictions prevent an exponential rebound. Public policies post-lockdown have a limited impact as they partly crowd out individual efforts. Compulsory mask wearing helps resume activity but has no impact on the epidemic. Communication that increases risk salience is more effective.", "qid": 44, "docid": "mqj5dzk9", "rank": 18, "score": 10.198200225830078}, {"content": "Title: COVID-19 and the Social Distancing Paradox: dangers and solutions Content: Background: Without proven effect treatments and vaccines, Social Distancing is the key protection factor against COVID-19. Social distancing alone should have been enough to protect again the virus, yet things have gone very differently, with a big mismatch between theory and practice. What are the reasons? A big problem is that there is no actual social distancing data, and the corresponding people behavior in a pandemic is unknown. We collect the world-first dataset on social distancing during the COVID-19 outbreak, so to see for the first time how people really implement social distancing, identify dangers of the current situation, and find solutions against this and future pandemics. Methods: Using a sensor-based social distancing belt we collected social distance data from people in Italy for over two months during the most critical COVID-19 outbreak. Additionally, we investigated if and how wearing various Personal Protection Equipment, like masks, influences social distancing. Results: Without masks, people adopt a counter-intuitively dangerous strategy, a paradox that could explain the relative lack of effectiveness of social distancing. Using masks radically changes the situation, breaking the paradoxical behavior and leading to a safe social distance behavior. In shortage of masks, DIY (Do It Yourself) masks can also be used: even without filtering protection, they provide social distancing protection. Goggles should be recommended for general use, as they give an extra powerful safety boost. Generic Public Health policies and media campaigns do not work well on social distancing: explicit focus on the behavioral problems of necessary mobility are needed.", "qid": 44, "docid": "vnc1iay1", "rank": 19, "score": 10.156000137329102}, {"content": "Title: COVID-ABS: An Agent-Based Model of COVID-19 Epidemic to Simulate Health and Economic Effects of Social Distancing Interventions Content: The COVID-19 pandemic due to the SARS-CoV-2 coronavirus has directly impacted the public health and economy worldwide. To overcome this problem, countries have adopted different policies and non-pharmaceutical interventions for controlling the spread of the virus. This paper proposes the COVID-ABS, a new SEIR (Susceptible-Exposed-Infected-Recovered) agent-based model that aims to simulate the pandemic dynamics using a society of agents emulating people, business and government. Seven different scenarios of social distancing interventions were analyzed, with varying epidemiological and economic effects: (1) do nothing, (2) lockdown, (3) conditional lockdown, (4) vertical isolation, (5) partial isolation, (6) use of face masks, and (7) use of face masks together with 50% of adhesion to social isolation. In the impossibility of implementing scenarios with lockdown, which present the lowest number of deaths and highest impact on the economy, scenarios combining the use of face masks and partial isolation can be the more realistic for implementation in terms of social cooperation. The COVID-ABS model was implemented in Python programming language, with source code publicly available. The model can be easily extended to other societies by changing the input parameters, as well as allowing the creation of a multitude of other scenarios. Therefore, it is a useful tool to assist politicians and health authorities to plan their actions against the COVID-19 epidemic.", "qid": 44, "docid": "cenc2u15", "rank": 20, "score": 10.144000053405762}, {"content": "Title: COVID-19: Taiwan\u2019s epidemiological characteristics and public and hospital responses Content: BACKGROUND: Coronavirus disease 19 (COVID-19) is a global health threat with significant medical, economic, social and political implications. The optimal strategies for combating COVID-19 have not been fully determined and vary across countries. METHODS: By the end of February 2020 in Taiwan, 2,150 patients received diagnostic COVID-19 testing and 39 confirmed cases were detected. This is a relatively lower rate of infection compared to other Asian countries. In this article, we summarize the epidemiological characteristics of the 39 infected patients as well as public and hospital responses to COVID-19. RESULTS: Thirty-nine COVID-19 cases and one death have been confirmed in Taiwan. Seventeen of these patients were infected by family members or in hospital wards, emphasizing how COVID-19 is mostly spread by close contact. We examined how hospital have responded to COVID-19, including their implementation of patient route control, outdoor clinics, hospital visit restrictions and ward and staff modifications. We also studied the public\u2019s use of face masks in response to COVID-19. These strategies may reduce the spread of COVID-19 in other countries. CONCLUSION: The emergence and spread of COVID-19 is a threat to health worldwide. Taiwan has reported lower infected cases and its strategies may contribute to further disease prevention and control.", "qid": 44, "docid": "9o0sjnml", "rank": 21, "score": 10.082799911499023}, {"content": "Title: Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach() Content: The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. \u201cAssortment\u201d within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.", "qid": 44, "docid": "dt2pew66", "rank": 22, "score": 10.072099685668945}, {"content": "Title: Strategies for Rational Use of Personal Protective Equipment (PPE) Among Healthcare Providers During the COVID-19 Crisis Content: As the coronavirus 2019 (COVID-19) began spreading globally with no clear treatment in sight, prevention became a major part of controlling the disease and its effects. COVID-19 spreads from the aerosols of an infected individual whether they are showing any symptoms or not. Therefore, it becomes nearly impossible to point exactly where the patient is. This is where personal protective equipment (PPE) comes in. These are masks, respirators, gloves, and in hospitals where the contact with the infected and confirmed patient is direct, also gowns or body covers. The PPEs play a major role in the prevention and control of the COVID-19. The PPE is able to prevent any invasion of the virus particles into the system of an individual which is why it is an essential item to have for healthcare workers. Due to the high demand for PPEs all around the world, it is important to optimize the use of protective gear and ration the supplies so that the demand are met. However, there are guidelines recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to maintain the supply in the wake of this increased demand of PPE, how the manufacturers should track their supplies, and how the recipients should manage them. Various strategies can be used to increase the re-use of PPEs during the COVID-19 pandemic that has modified the donning and doffing procedure.", "qid": 44, "docid": "7el8o6qq", "rank": 23, "score": 10.071200370788574}, {"content": "Title: SurviveCovid-19 -- A Game for Improving Awareness of Social Distancing and Health Measures for Covid-19 Pandemic Content: Pandemics have threatened human race many a times. One of the most important tasks during a pandemic is to bring awareness among people. Bringing awareness contributes a lot in controlling any pandemic. Covid-19 has been causing severe loss to the human race. Considering the mode of spread and the level of severity of this disease, it is extremely important to make people aware of various safety precautions such as using sanitizers and masks and maintaining social distancing, that are to be followed to prevent the disease and break the chain of spread. This mode of educating individuals about the disease is being widely carried out as announcements through online or physical awareness campaigns, advertisements in the media and so on. The younger generations in the present day spend considerably more time on mobile phones and games. However, there are very few mobile applications or games, aimed to bring awareness about a pandemic, which is much lesser in case of Covid-19. Also, considering the lockdown scenario across the world, games also act as a good pass time indoors. Hence, we propose a 2D survival based game, SurviveCovid-19, aimed to educate people about safety precautions to be taken for Covid-19 outside their homes, by incorporating social distancing and usage of masks and sanitizers in the game. SurviveCovid-19 has been designed as an Android based mobile game and has been evaluated through a remote qualitative user survey, with 20 volunteers. The results of the survey are promising with all the questions of survey having mean value greater than 3.6.", "qid": 44, "docid": "d6w8fu3b", "rank": 24, "score": 10.069499969482422}, {"content": "Title: Is wearing a face mask safe for people with epilepsy? Content: Since December 2019, the world has been experiencing a catastrophic pandemic of coronavirus disease (COVID-19) caused by SARS-CoV2. This virus primarily targets the human respiratory system. Available information suggests that people with epilepsy (PWE) are not at higher risk of being infected by the virus, nor of more severe COVID-19 manifestations, as a result of the epilepsy alone. However, COVID-19 is a serious disease that currently has no effective treatment or vaccine. A face mask is probably effective in preventing the spread of a respiratory pathogen, at least to some extent. So, should we recommend wearing a face mask to all during a pandemic of respiratory infectious disease (e.g., COVID-19) without any precautions or exemptions? While concrete evidence is lacking, if we consider that wearing a face mask may simulate hyperventilation, at least to some extent, we would probably avoid recommending this practice indiscriminately to all PWE. On the other hand, in the absence of any proven treatment or vaccine to combat COVID-19, prevention is the best available strategy and it is probably not reasonable to suggest avoid wearing face masks in PWE under any circumstances. Logically, PWE do not need to wear a face mask most of the time, as long as there is no close contact with others, especially during intense physical activities such as exercise. To the contrary, it is probably more advantageous to wear a face mask in crowded locations, with intermittent breaks in safe locations, away from others.", "qid": 44, "docid": "lq7bh1sl", "rank": 25, "score": 10.05090045928955}, {"content": "Title: COVID-19: emerging protective measures Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 44, "docid": "qi8x5yaq", "rank": 26, "score": 9.931099891662598}, {"content": "Title: COVID-19: emerging protective measures. Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 44, "docid": "tfrawa9z", "rank": 27, "score": 9.931098937988281}, {"content": "Title: Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda Content: Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.", "qid": 44, "docid": "zwyueevh", "rank": 28, "score": 9.891900062561035}, {"content": "Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "qid": 44, "docid": "uc37poce", "rank": 29, "score": 9.851799964904785}, {"content": "Title: The COVID-19 pandemic: biological evolution, treatment options and consequences Content: The spread of novel coronavirus SARS-CoV-2, the cause of the pandemic COVID-19 has emerged as a global matter of concern in the last couple of months. It has rapidly spread around the globe, which initially began in the city of Wuhan, People\u2019s Republic of China and is hypothesized to originate from the group of Rhinolophus bats. Till date, there has been no clinically proven vaccine against the SARS-CoV-2 and thus the doctors are employing the other well-known techniques, which have previously successfully tackled similar other human coronaviruses. To prevent the further spread of COVID-19, doctors are advising isolation of the infected patients, and also regular washing of hands and the use of face mask for the common people. In the wake of the COVID-19 outbreak, the countries are going for nationwide lockdown as the only preventive measure to avert community transmission of this disease, which is having economic, social and psychological effect on the general mass. Therefore, this comprehensive review article encapsulates the biological evolution of human coronaviruses, probable treatment and control strategies to combat COVID-19 and, its impact on human life.", "qid": 44, "docid": "6bzfptbs", "rank": 30, "score": 9.789899826049805}, {"content": "Title: Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma Content: Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are \"low cost\" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.", "qid": 44, "docid": "1c3fpazy", "rank": 31, "score": 9.770099639892578}, {"content": "Title: Personal protective equipment and possible routes of airborne spread during the COVID\u201019 pandemic Content: We welcomed Professor Cook's article clarifying the use of personal protective equipment (PPE) in protecting staff during the current COVID-19 pandemic [1]. There remains considerable debate about the extent to which airborne spread of SARS-CoV-2 occurs. Small droplets (< 5\u00b5m) are thought to remain suspended in the air and could theoretically be inhaled into the lungs causing infection [2]. Loose fitting \"surgical\" masks will not prevent such inhalation and only a tight-fitting filtering mask is adequate. Conversely larger (> 5\u00b5m) particles do not remain suspended in the air [2] and can only cause infection if they are immediately inhaled, or after contact with a surface they land on.", "qid": 44, "docid": "ve34oyz0", "rank": 32, "score": 9.721500396728516}, {"content": "Title: A Model for the Testing and Tracing Needed to Suppress COVID-19 Content: This paper presents a simple mathematical model that answers how much testing and tracing we need to do to suppress new surges of COVID-19 infections after reopening. We derived the model by modifying the SEIR model taking into the effects of testing and tracing. The following equation is one of the essential outcomes of the model: {rho}>(R0S/N-1)/(D(1+{eta}R0)) Where {rho} is the percentage of infectious people that have to be detected per day, R0 is the basic reproduction number, S/N is the percentage of the susceptible population over the entire population, D is the length of the infectious period, and {eta} is the percentage of close contacts that have to be traced. If the above equation is satisfied, we can bring the effective reproduction number Re to below 1 to get the transmission suppressed. This model demonstrates that together with social-distancing measures such as wearing masks in public, with a reasonable amount of testing and tracing, we may suppress the COVID-19 transmission for good. For example, if social distancing measures can bring R0 to below 1.2, for D being 10 days, in places where 15% people have developed antibodies, we can suppress the transmission by detecting only 0.13% of the infectious population daily while tracing 50% of their close contacts. The model provides intuitive insights and quantitative guidance for policymakers and public health practitioners to deploy the testing and tracing resources optimally.", "qid": 44, "docid": "b2yalnrx", "rank": 33, "score": 9.678299903869629}, {"content": "Title: Messaging Mask Wearing During the COVID-19 Crisis: Ideological Differences Content: As the U.S. Government works to slow the spread of the novel coronavirus, messaging is important in getting individuals to comply with public health recommendations, especially as the response from the public seems to be polarized along partisan and ideological lines. Using a recent Centers for Disease Control recommendation of wearing facemasks, I use Regulatory Focus Theory to predict that conservatives will be more responsive to messages related to promotion, while liberals are more responsive to messages related to prevention. Using a pre-registered experimental design, I find no evidence that prevention messages influence attitudes toward mask wearing. Promotion messages, however, cause conservatives to become less supportive of mask wearing, in contrast to theoretical predictions. These findings suggest that, related to messaging about mask wearing, strong ideological differences do not emerge related to the focus of the message.", "qid": 44, "docid": "k5nfy43y", "rank": 34, "score": 9.644800186157227}, {"content": "Title: How Right-Leaning Media Coverage of COVID-19 Facilitated the Spread of Misinformation in the Early Stages of the Pandemic in the U.S. Content: We have yet to know the ultimate global impact of the novel coronavirus pandemic. However, we do know that delays, denials and misinformation about COVID-19 have exacerbated its spread and slowed pandemic response, particularly in the U.S. (e.g., Abutaleb et al., 2020).", "qid": 44, "docid": "2r0a357c", "rank": 35, "score": 9.634699821472168}, {"content": "Title: COVID-19 and Other Pandemics: How Might They Be Prevented? Content: Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now Coronavirus Disease 2019 (COVID-19) have arisen, and given the current absence of highly effective approved vaccines or drugs, brute-force approaches involving physical barriers are being used to counter virus spread. A major basis for physical protection from respiratory infections is eye, nose, and mouth protection. However, eye protection with goggles is problematic due to \u201cfogging\u201d, while nose/mouth protection is complicated by the breathing difficulties associated with non-valved respirators. Here, we give a brief review of the origins and development of face masks and eye protection to counter respiratory infections on the basis of experiments conducted 100 years ago, work that was presaged by the first use of personal protective equipment, \u201cPPE\u201d, by the plague doctors of the 17(th) Century. The results of the review lead to two conclusions: first, that eye protection using filtered eye masks be used to prevent ocular transmission; second, that new, pre-filtered, valved respirators be used to even more effectively block viral transmission.", "qid": 44, "docid": "9k2de2sd", "rank": 36, "score": 9.62660026550293}, {"content": "Title: COVID-19 and Other Pandemics: How Might They Be Prevented? Content: Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now Coronavirus Disease 2019 (COVID-19) have arisen, and given the current absence of highly effective approved vaccines or drugs, brute-force approaches involving physical barriers are being used to counter virus spread. A major basis for physical protection from respiratory infections is eye, nose, and mouth protection. However, eye protection with goggles is problematic due to \"fogging\", while nose/mouth protection is complicated by the breathing difficulties associated with non-valved respirators. Here, we give a brief review of the origins and development of face masks and eye protection to counter respiratory infections on the basis of experiments conducted 100 years ago, work that was presaged by the first use of personal protective equipment, \"PPE\", by the plague doctors of the 17th Century. The results of the review lead to two conclusions: first, that eye protection using filtered eye masks be used to prevent ocular transmission; second, that new, pre-filtered, valved respirators be used to even more effectively block viral transmission.", "qid": 44, "docid": "ah29pm89", "rank": 37, "score": 9.626599311828613}, {"content": "Title: Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France Content: Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.", "qid": 44, "docid": "smndijko", "rank": 38, "score": 9.551300048828125}, {"content": "Title: COVID-19 Epidemic in Algeria: Assessment of the implemented preventive strategy Content: Abstract Since the spread of the COVID-19 epidemic in China, several preventive strategies have been implemented worldwide to fight against the spread of the virus, in Algeria the control actions have been mainly social distancing, movement restriction, quarantine and lockdown. In order to assess the preventive strategy adopted in Algeria, we studied three zones whole Algeria, Blida region, and whole Algeria except Blida, we used as a indicator the basic reproduction number R0, we compared the mean R0-before and R0-after the implementation of the mitigation measures using bivariate analysis, then we used the results we found to estimate the number of COVID-19 cases avoided by these measures, then after, we predicted the peak of the first wave of the epidemic. We note that the decrease in R0 after the preventive measures implementation was statistically significant, p value < 10-4, in the three areas, thus, the preventive strategy in Algeria has been effective in its entirety. Our projection revealed that 15613 cases of COVID-19 were avoided in 14 days, from April 6, to April 19, 2020, in the whole country, and 1747 cases were prevented in Blida during the same period. We estimate that the peak of the first wave of the epidemic in Algeria will be reached with herd immunity of 15.93% as of November 2020, however, at least 56% of people with protective immunity would be needed to be sufficient to avoid a second wave. The used method to carry out the evaluation has given us a good overview, but, R0 is not the only factor to consider when estimating the burden of the epidemic, to do that, the number of daily admissions to intensive care units and hospitalizations remain good indicators. In order to better the epidemic control in Algeria, it is possible to act on contact efficacy rate by adding an instruction to wear medical mask by ordinary population outside, this measure has been reported to be effective in some countries. To conclude, it is good to keep in mind that a new way of life based on good hygiene habits and social distancing must therefore be in place and adopted by the population for at least several months, otherwise the demand for health care will exceed the availability. Keywords: COVID-19, Algeria, preventive strategy assessment, R0, epidemic peak.", "qid": 44, "docid": "dgha14wo", "rank": 39, "score": 9.483499526977539}, {"content": "Title: [Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia]. Content: Definite evidence has shown that the novel coronavirus (COVID-19) could be transmitted from person to person, so far more than 1 700 bedside clinicians have been infected. A lot of respiratory treatments for critically ill patients are deemed as high-risk factors for nosocomial transmission, such as intubation, manual ventilation by resuscitator, noninvasive ventilation, high-flow nasal cannula, bronchoscopy examination, suction and patient transportation, etc, due to its high possibility to cause or worsen the spread of the virus. As such, we developed this consensus recommendations on all those high-risk treatments, based on the current evidence as well as the resource limitation in some areas, with the aim to reduce the nosocomial transmission and optimize the treatment for the COVID-19 pneumonia patients. Those recommendations include: (1)Standard prevention and protection, and patient isolation; (2)Patient wearing mask during HFNC treatment; (3)Using dual limb ventilator with filters placed at the ventilator outlets, or using heat-moisture exchanger (HME) instead of heated humidification in single limb ventilator with HME placed between exhalation port and mask; avoid using mask with exhalation port on the mask; (4)Placing filter between resuscitator and mask or artificial airway; (5)For spontaneous breathing patients, placing mask for patients during bronchoscopy examination; for patients receiving noninvasive ventilation, using the special mask with bronchoscopy port to perform bronchoscopy; (6)Using sedation and paralytics during intubation, cuff pressure should be maintained between 25-30 cmH(2)O(1 cmH(2)O=0.098 kPa); (7)In-line suction catheter is recommended and it can be used for one week; (8)Dual-limb heated wire circuits are recommended and only changed with visible soiled; (9)For patients who need breathing support during transportation, placing an HME between ventilator and patient; (10)PSV is recommended for implementing spontaneous breathing trial (SBT), avoid using T-piece to do SBT. When tracheotomy patients are weaned from ventilator, HME should be used, avoid using T-piece or tracheostomy mask. (11)Avoid unnecessary bronchial hygiene therapy; (12) For patients who need aerosol therapy, dry powder inhaler metered dose inhaler with spacer is recommended for spontaneous breathing patients; while vibrating mesh nebulizer is recommended for ventilated patients and additional filter is recommended to be placed at the expiratory port of ventilation during nebulization.", "qid": 44, "docid": "d5yc1rzs", "rank": 40, "score": 9.454500198364258}, {"content": "Title: [Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia]. Content: Definite evidence has shown that the novel coronavirus (COVID-19) could be transmitted from person to person, so far more than 1,700 bedside clinicians have been infected. A lot of respiratory treatments for critically ill patients are deemed as high-risk factors for nosocomial transmission, such as intubation, manual ventilation by resuscitator, noninvasive ventilation, high-flow nasal cannula, bronchoscopy examination, suction and patient transportation, etc, due to its high possibility to cause or worsen the spread of the virus. As such, we developed this consensus recommendations on all those high-risk treatments, based on the current evidence as well as the resource limitation in some areas, with the aim to reduce the nosocomial transmission and optimize the treatment for the COVID-19 pneumonia patients. Those recommendations include: (1) Standard prevention and protection, and patient isolation; (2) Patient wearing mask during HFNC treatment; (3) Using dual limb ventilator with filters placed at the ventilator outlets, or using heat-moisture exchanger (HME) instead of heated humidification in single limb ventilator with HME placed between exhalation port and mask; avoid using mask with exhalation port on the mask; (4) Placing filter between resuscitator and mask or artificial airway; (5) For spontaneous breathing patients, placing mask for patients during bronchoscopy examination; for patients receiving noninvasive ventilation, using the special mask with bronchoscopy port to perform bronchoscopy; (6) Using sedation and paralytics during intubation, cuff pressure should be maintained between 25-30 cmH(2)O; (7) In-line suction catheter is recommended and it can be used for one week; (8) Dual-limb heated wire circuits are recommended and only changed with visible soiled; (9. For patients who need breathing support during transportation, placing an HME between ventilator and patient; (10) PSV is recommended for implementing spontaneous breathing trial (SBT), avoid using T-piece to do SBT. When tracheotomy patients are weaned from ventilator, HME should be used, avoid using T-piece or tracheostomy mask. (11) Avoid unnecessary bronchial hygiene therapy; (12) For patients who need aerosol therapy, dry powder inhaler metered dose inhaler with spacer is recommended for spontaneous breathing patients; while vibrating mesh nebulizer is recommended for ventilated patients and additional filter is recommended to be placed at the expiratory port of ventilation during nebulization.", "qid": 44, "docid": "gdr1dhbd", "rank": 41, "score": 9.454499244689941}, {"content": "Title: [Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia] Content: Definite evidence has shown that the novel coronavirus (COVID-19) could be transmitted from person to person, so far more than 1,700 bedside clinicians have been infected. A lot of respiratory treatments for critically ill patients are deemed as high-risk factors for nosocomial transmission, such as intubation, manual ventilation by resuscitator, noninvasive ventilation, high-flow nasal cannula, bronchoscopy examination, suction and patient transportation, etc, due to its high possibility to cause or worsen the spread of the virus. As such, we developed this consensus recommendations on all those high-risk treatments, based on the current evidence as well as the resource limitation in some areas, with the aim to reduce the nosocomial transmission and optimize the treatment for the COVID-19 pneumonia patients. Those recommendations include: (1) Standard prevention and protection, and patient isolation; (2) Patient wearing mask during HFNC treatment; (3) Using dual limb ventilator with filters placed at the ventilator outlets, or using heat-moisture exchanger (HME) instead of heated humidification in single limb ventilator with HME placed between exhalation port and mask; avoid using mask with exhalation port on the mask; (4) Placing filter between resuscitator and mask or artificial airway; (5) For spontaneous breathing patients, placing mask for patients during bronchoscopy examination; for patients receiving noninvasive ventilation, using the special mask with bronchoscopy port to perform bronchoscopy; (6) Using sedation and paralytics during intubation, cuff pressure should be maintained between 25-30 cmH(2)O; (7) In-line suction catheter is recommended and it can be used for one week; (8) Dual-limb heated wire circuits are recommended and only changed with visible soiled; (9. For patients who need breathing support during transportation, placing an HME between ventilator and patient; (10) PSV is recommended for implementing spontaneous breathing trial (SBT), avoid using T-piece to do SBT. When tracheotomy patients are weaned from ventilator, HME should be used, avoid using T-piece or tracheostomy mask. (11) Avoid unnecessary bronchial hygiene therapy; (12) For patients who need aerosol therapy, dry powder inhaler metered dose inhaler with spacer is recommended for spontaneous breathing patients; while vibrating mesh nebulizer is recommended for ventilated patients and additional filter is recommended to be placed at the expiratory port of ventilation during nebulization.", "qid": 44, "docid": "ls3cqvz3", "rank": 42, "score": 9.454498291015625}, {"content": "Title: Would everyone wearing face masks help us slow the pandemic? Content: As cases of coronavirus disease 2019 (COVID-19) ballooned last month, people in Europe and North America scrambled to get their hands on surgical masks to protect themselves Health officials jumped in to discourage them, worried about the limited supply of masks for health care personnel \u201cSeriously people-STOP BUYING MASKS!\u201d began a 29 February tweet from U S Surgeon General Jerome Adams The World Health Organization and U S Centers for Disease Control and Prevention (CDC) have both said that only people with COVID-19 symptoms and those caring for them should wear masks But some health experts, including the director of the Chinese Center for Disease Control and Prevention, think that\u2019s a mistake Health authorities in parts of Asia have encouraged all citizens to wear masks in public to prevent the spread of the virus, regardless of whether they have symptoms And the Czech Republic took the uncommon step last week of making nose and mouth coverings mandatory in public spaces, prompting a grassroots drive to hand make masks", "qid": 44, "docid": "ydazitgp", "rank": 43, "score": 9.415499687194824}, {"content": "Title: Estimating a breakpoint in the pattern of spread of COVID-19 in South Korea Content: OBJECTIVES: Amid the global coronavirus disease 2019 (COVID-19) crisis, South Korea has been lauded for successfully preventing the spread of this infectious disease, which may be due to the aggressive implementation of preventive policies. This study was performed to evaluate the pattern of spread of COVID-19 in South Korea considering the potential impact of policy interventions on transmission rates. METHODS: A SIR (susceptible-infected-removed) model with a breakpoint that allows a change in transmission rate at an unknown point was established. Estimated trajectories of COVID-19 from SIR models with and without a breakpoint were compared. RESULTS: The proposed model with a break fitted the actual series of infection cases much better than the classic model. The estimated breakpoint was March 7, 2020 and the transmission rate dropped by 0.23 after the breakpoint. A counterfactual study based on our estimate indicated that the number of infected could have reached 2 500 000 compared to the peak of 8000 in the observed series. CONCLUSIONS: It is critical to consider a change in the transmission rate to evaluate the trajectory of spread of COVID-19 in South Korea. Our estimation and counterfactual experiments indicate that public health interventions may play a role in determining the pattern of spread of infectious diseases.", "qid": 44, "docid": "4ouz10kb", "rank": 44, "score": 9.39780044555664}, {"content": "Title: Epidemiology reveals mask wearing by the public is crucial for COVID-19 control Content: Abstract Objective The pandemic 2019 Coronavirus disease (COVID-19) is the greatest concern globally. Here we analyzed the epidemiological features of China, South Korea, Italy and Spain to find out the relationship of major public health events and epidemiological curves. Study design In this study we describe and analyze the epidemiological characteristics of COVID-19 in and outside China. We use GAM to generate the epidemiological curves and simulate infection curves with reported incubation period. Results The epidemiological curved derived from the GAM suggested that the infection curve can reflect the public health measurements sensitively. Under the massive actions token in China, the infection curve flattened at 23rd of January. While surprisingly, even before Wuhan lockdown and first level response of public emergency in Guangdong and Shanghai, those infection curve came to the reflection point both at 21st of January, which indicated the mask wearing by the public before 21st Jan were the key measure to cut off the transmission. In the countries outside China, infection curve also changed in response to measures, but its rate of decline was much smaller than the curve of China's. Conclusion The present analysis comparing the epidemiological curves in China, South Korea, Italy and Spain supports the importance of mask wearing by the public. Analysis of the infection curve helped to clarify the impact of important public health events, evaluate the efficiencies of prevention measures, and showed wearing masks in public resulted in significantly reduced daily infected cases.", "qid": 44, "docid": "fsis95hd", "rank": 45, "score": 9.33650016784668}, {"content": "Title: In bid to rapidly expand coronavirus testing, U.S. agency abruptly changes rules ;Science ;AAAS Content: The Food and Drug Administration (FDA) today recommended a dramatic shift in how it implements regulations that control whether laboratories can use diagnostic kits created in-house to test for infections of coronavirus-2019 (COVID-19) \u201cWe issued a policy this morning that allows us to have a lot of flexibility around the development of diagnostic tests,\u201d said FDA Commissioner Stephen Hahn at a White House briefing with President Donald Trump this afternoon \u201cWe expect this policy to have a significant impact \u201d The change could greatly expand the number of laboratories able to do coronavirus testing The U S government has come under severe criticism for not providing nearly enough tests needed to understand the extent of spread in the population A test kit produced and distributed by the U S Centers for Disease Control and Prevention (CDC) was shelved after state and local lab trying it out discovered that it contained a faulty reagent As a result, many labs that have the capability to test themselves have not been allowed to do so The new recommendations focus on \u201chigh-complexity testing laboratories\u201d that are certified under federal rules known as Clinical Laboratory Improvement Amendments This group of facilities includes many hospital labs, like the one that epidemiologist Michael Mina works at Brigham and Women\u2019s Hospital in Boston \u201cEssentially it\u2019s opening up a clear and concise avenue for labs like the one at Brigham and Women\u2019s,\u201d says Mina \u201cIt\u2019s what I\u2019ve been advocating for a month now \u201d", "qid": 44, "docid": "jsbdmnx5", "rank": 46, "score": 9.332099914550781}, {"content": "Title: Evaluating Protective Effects of Vaccination Content: Evaluating the direct protective effects of vaccines in the individuals who were vaccinated has been the focus of vaccine studies over the past century. Generally, interest has been in the ability of vaccination to prevent or to ameliorate disease rather than to prevent infection (Clements-Mann 1998). Ascertainment of cases is often done by finding suspected cases in the population under study in people who exhibit a set of symptoms. The suspected cases are then tested for biological confirmation of the infectious agent of interest. Alternatively, surveillance can ascertain cases reported in central registries. However they are ascertained, with most vaccines, clinical disease is the primary outcome of interest. When ascertainment is on clinical cases, most asymptomatic infections may go undetected. A different situation arises when infection is the primary outcome. To ascertain infections in asymptomatic people, an active follow-up method of testing asymptomatic people is needed. In this chapter we consider estimation and inference for direct protective effects of vaccination, VE(S) and VE(SP), in studies that do not condition on exposure to infection.We consider aspects of the design of such studies. Several examples of randomized, double-blind (double-masked) controlled vaccine trials illustrate the standard approach to design and analysis of such studies. Our choice of studies to present was motivated largely because of their use as illustrations in other sections of the book. Most randomized and pivotal studies of vaccines have been based on VE(SP) or VE(S). Much has been written on studies to meet the approval of the regulatory agencies, and the design of clinical trials generally. Our goal here is to consider how VE(S) and VE(SP) relate to other measures of vaccine effects within the dependent happening context, and consider a few design considerations. Because VE(S) and VE(SP) do not condition on exposure to infection, assumptions about the relative exposure opportunity in the vaccine and control groups are important.", "qid": 44, "docid": "zznjqdx2", "rank": 47, "score": 9.330900192260742}, {"content": "Title: Significance of super spreader events in COVID-19. Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 44, "docid": "na3vrf5q", "rank": 48, "score": 9.302800178527832}, {"content": "Title: Significance of super spreader events in COVID-19 Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 44, "docid": "p48bw6s4", "rank": 49, "score": 9.302799224853516}, {"content": "Title: COVID-19 Disease in Children: What Dentists Should Know and Do to Prevent Viral Spread. The Italian Point of View Content: Coronavirus disease 2019 (COVID-19) has spread rapidly across the globe, becoming a major public health challenge not for China only, but also for countries around the world. Despite worldwide efforts to contain viral spread, the outbreak has not been stopped yet. Among healthcare personnel, dentists seem to be at elevated risk of exposure to COVID-19. This risk is even more serious in pediatric dentistry, since affected children, frequently, present an asymptomatic, mild or moderate clinical viral infection and, therefore, they may play a major role in community-based COVID-19 transmission. To date, despite no universal guidelines are available for dental procedures in pediatric dentistry during COVID-19 outbreak, routine dental practice should be postponed and only severe dental emergencies must be treated. In the case of a dental emergency, involving a pediatric patient, dentists should be aware of which recommended management protocol can be adopted during the practice to protect patient health, to safeguard their-self and to prevent viral transmission. The aim of this paper is to provide clinical recommendations, presenting a needed tool for dentists to allow a valid and safe how-to-do protocol. Pediatric dentists should keep a high level of awareness to help patients, minimize risk and prevent viral spread.", "qid": 44, "docid": "w524alg0", "rank": 50, "score": 9.30150032043457}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence. Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 44, "docid": "1h5a4bit", "rank": 51, "score": 9.249500274658203}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 44, "docid": "clt4l6wz", "rank": 52, "score": 9.249499320983887}, {"content": "Title: How effective can homemade face masks be? Content: With cases of COVID-19 growing rapidly in the US and evidence mounting that the virus responsible, SARS-CoV-2, can be spread by infected people before they develop symptoms, the US Centers for Disease Control and Prevention recommended April 3 that people wear cloth face coverings in public places This guidance is a shift from the center\u2019s previous position that healthy people needed to wear masks only when caring for a sick person The recommendation also follows recent calls by experts on social media and other platforms for the general public to don nonmedical, cloth masks to help reduce the transmission of the novel coronavirus \u201cMembers of the general public should wear non-medical fabric face masks when going out in public in one additional societal effort to slow the spread of the virus down,\u201d Tom Inglesby, director of the Johns Hopkins Center for Health Security, tweeted March 29 These experts hope the View: PDF ;Full Text HTML", "qid": 44, "docid": "zfea3qg7", "rank": 53, "score": 9.241600036621094}, {"content": "Title: Defending against the Novel Coronavirus (COVID-19) Outbreak: How Can the Internet of Things (IoT) help to save the World? Content: \u2022 IoT within infectious disease epidemiology is an emerging field of research, however the ubiquitous availability of smart technologies, as well as increased risks of infectious disease spread through the globalization and interconnectedness of the world necessitates its use for predicting, preventing and controlling emerging infectious diseases; \u2022 Considering the present situation in China, IoT based smart disease surveillance systems have the potential to be a major breakthrough in efforts to control the current pandemic. With much of the infrastructure itself in place already (i.e. smartphones, wearable technologies, internet access) the role this technology can have in limiting the spread of the pandemic involves only the collection and analysis of data already gathered. \u2022 More research must be carried out for the development of automated and effective alert systems to provide early and timely detection of outbreaks of such diseases in order to reduce morbidity mortality and prevent global spread.", "qid": 44, "docid": "e1ih1fkx", "rank": 54, "score": 9.228500366210938}, {"content": "Title: Defending against the Novel Coronavirus (COVID-19) Outbreak: How Can the Internet of Things (IoT) help to save the World? Content: \u00e2\u0080\u00a2IoT within infectious disease epidemiology is an emerging field of research, however the ubiquitous availability of smart technologies, as well as increased risks of infectious disease spread through the globalization and interconnectedness of the world necessitates its use for predicting, preventing and controlling emerging infectious diseases\u00e2\u0080\u00a2Considering the present situation in China, IoT based smart disease surveillance systems have the potential to be a major breakthrough in efforts to control the current pandemic. With much of the infrastructure itself in place already (i.e. smartphones, wearable technologies, internet access) the role this technology can have in limiting the spread of the pandemic involves only the collection and analysis of data already gathered.\u00e2\u0080\u00a2More research must be carried out for the development of automated and effective alert systems to provide early and timely detection of outbreaks of such diseases in order to reduce morbidity mortality and prevent global spread.", "qid": 44, "docid": "oj32vpqn", "rank": 55, "score": 9.228499412536621}, {"content": "Title: Do we have enough evidence how seasonal influenza is transmitted and can be prevented in hospitals to implement a comprehensive policy? Content: PURPOSE: To identify if there is enough evidence at low risk-of-bias to prevent influenza transmission by vaccinating health-care workers (HCWs), patients and visitors; screening for laboratory-proven influenza all entering hospitals; screening asymptomatic individuals; identifying influenza supershedders; hand-washing and mask-wearing by HCWs, patients and visitors; and cleaning hospital rooms and equipment. PRINCIPAL RESULTS: Vaccination reduces influenza episodes of vaccinated (4.81/100 HCW) compared to unvaccinated (7.54/100) HCWs/influenza season. A Cochrane review found for inactivated vaccines the Number Needed to Vaccinate (NNV) = 71 (95%CI 64%, 80%) for adults 18\u201360 (same age as HCWs) to prevent laboratory-proven influenza. There are no RCTs of screening HCWs, patients, visitors and influenza supershedders to prevent transmission. None of four RCTs of HCWs mask-wearing (two directly observed, two not) showed an effect because they were underpowered either due to small size or low circulation of influenza. Hospital rooms and equipment can effectively be cleaned of influenza by many chemicals and hydrogen peroxide vapor machines but the cleaning cycle needs shortening to increase the likelihood of adoption. MAJOR CONCLUSIONS: HCW vaccination is a partial solution with current vaccination levels. There are no RCTs of screening HCWs, patients and visitors demonstrating preventing influenza transmission. Only one study costed furloughing HCWs with influenza and no RCTs have identified benefits of isolating influenza supershedders. RCTs of directly- and electronically continuously-observed mask-wearing and hand-hygiene and RCTs of incentives for meticulous hygiene are required. RCTs of engineering solutions (external venting, frequent room air changes) are needed. A wide range of chemicals effectively cleans hospital rooms and equipment from influenza. Hydrogen peroxide vapor is effective against influenza and a wide range of bacterial pathogens with patient room changes, and clean areas cleaners do not clean but its cleaning cycle needs shortening to increase the likelihood of adoption of cleaning rooms vacated by influenza patients.", "qid": 44, "docid": "480bzpi1", "rank": 56, "score": 9.181400299072266}, {"content": "Title: TRENDS IN PERCEPTION OF COVID-19 IN POLISH INTERNET Content: INTRODUCTION: Due to the spread of SARS-CoV-2 virus responsible for COVID-19 disease, there is an urgent need to analyse COVID-19 epidemic perception in Poland. This study aims to investigate social perception of coronavirus in the Internet media during the epidemic. It is a signal report highlighting the main issues in public perception and medical commutation in real time. METHODS: We study the perception of COVID-19 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet on platforms: Google, Twitter, YouTube, Wikipedia and electronic media represented by Event Registry, from January 2020 to 29.04.2020 (before and after official introduction to Poland on 04.03.20). We present trend analysis with a support of natural language processing techniques. RESULTS: We identified seven temporal major clusters of interest on the topic COVID-19: 1) Chinese, 2) Italian, 3) Waiting, 4) Mitigations, 5) Social distancing and Lockdown, 6) Anti-crisis shield, 7) Restrictions releasing. There was an exponential increase of interest when the Polish government declared war against disease around 11/12.03.20 with a massive mitigation program. Later on, there was a decay in interest with additional phases related to social distancing and an anti-crisis legislation act with local peaks. We have found that declarations of mitigation strategies by the Polish prime minister or the minister of health gathered the highest attention of Internet users. So enacted or in force events do not affect interest to such extent. Traditional news agencies were ahead of social media (mainly Twitter) in dissemination of information. We have observed very weak or even negative correlations between a colloquial searching term antiviral mask in Google, encyclopaedic definition in Wikipedia SARS-CoV-2 as well official incidence series, implying different mechanisms governing the search for knowledge, panic related behaviour and actual risk of acquiring infection. CONCLUSIONS: Traditional and social media do not only reflect reality, but also create it. Risk perception in Poland is unrelated to actual physical risk of acquiring COVID-19. As traditional media are ahead of social media in time, we advise to choose traditional news media for a quick dissemination of information, however for a greater impact, social media should be used. Otherwise public information campaigns might have less impact on society than expected.", "qid": 44, "docid": "p22qn6cl", "rank": 57, "score": 9.17959976196289}, {"content": "Title: Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19 Content: OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.", "qid": 44, "docid": "9uxfxry4", "rank": 58, "score": 9.16100025177002}, {"content": "Title: Facial protection in the era of COVID-19: A narrative review Content: We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different types of facial protection measures, including masks, needed both for the public and the healthcare workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air-purifying respirators (PAPR), and the skin health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 44, "docid": "6n5gnow1", "rank": 59, "score": 9.160400390625}, {"content": "Title: Facial protection in the era of COVID\u201019: a narrative review Content: We live in extraordinary times, where COVID\u201019 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin\u2010health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID\u201019 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 44, "docid": "kqlra788", "rank": 60, "score": 9.160399436950684}, {"content": "Title: Facial protection in the era of COVID-19: a narrative review Content: We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 44, "docid": "uep2tfnu", "rank": 61, "score": 9.160398483276367}, {"content": "Title: Leveraging Wettability Engineering to Develop Three-Layer DIY Face Masks From Low-Cost Materials Content: With the rapid spread of COVID-19 worldwide, the demand for appropriate face masks in the market has also skyrocketed. To ease strain on the supply of masks to the essential healthcare sector, it has become imperative that ordinary people rely more on home-made masks that can be easily put together using commonly available materials, while at the same time performing reasonably at arresting the ingress or egress of airborne droplets. Here, we propose a simple do-it-yourself (DIY) method for preparing a three-layered face mask that deploys two hydrophobic polypropylene nonwoven layers interspaced with a hydrophilic cellulosic cloth. The first hydrophobic layer, facing the user, allows high-momentum droplets (e.g., expelled by a sneeze or cough) to pass through and get absorbed in the next hydrophilic layer, thereby keeping the skin in contact with the mask dry and comfortable. The third (outermost) hydrophobic layer prevents penetration of the liquids from the middle layer to the outside, and also arrests any airborne droplets on its exterior. Simple tests show that our masks perform better in arresting the droplet transmission as compared to surgical masks available in the market. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41403-020-00115-9) contains supplementary material, which is available to authorized users.", "qid": 44, "docid": "fpps1ux6", "rank": 62, "score": 9.144499778747559}, {"content": "Title: \u2018Masking the evidence\u2019: perspectives of the COVID\u201019 pandemic Content: The COVID\u201019 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID\u201019 (WHO 2020a).", "qid": 44, "docid": "f9syysdw", "rank": 63, "score": 9.123299598693848}, {"content": "Title: 'Masking the evidence': perspectives of the COVID-19 pandemic Content: The COVID-19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID-19 (WHO 2020a).", "qid": 44, "docid": "sjenehbl", "rank": 64, "score": 9.123298645019531}, {"content": "Title: Our education, our concerns: The impact on medical student education of COVID\u201019 Content: March 2020, it seemed as if my world was turned upside down. I opened an email from my medical school dean of student affairs stating: Match Day, cancelled. The day that would determine where we trained as postgraduate residents, the day my class had worked towards for 4 years, cancelled due to this new virus that we seemed to know so little about: COVID-19. However, as important as that day was to my fellow 4th year medical students and I, we quickly learned that the impact was much larger. What about our electives, our mandatory rotations, and even the Sub-Internship's students still had to complete? Not just that, but \"what can we do to help,\" became a common statement echoed by all students. We don't want to see this as a detriment to our education but a learning experience. A learning experience for how to be best prepared to help now, and in the future. One way to help is to make changes in medical education to ensure all students are still getting the absolute best level of education possible. This starts with recognizing the options we have and utilizing all of the tools at our disposal, despite the boundaries created by COVID-19.", "qid": 44, "docid": "xb50599v", "rank": 65, "score": 9.113499641418457}, {"content": "Title: Impact of anxiety associated with COVID 19 on tinnitus Content: Background We investigated how the anxiety associated with COVID 19 impacts the severity of tinnitus and the outcomes of tinnitus therapy. Methods and Findings A retrospective research design was used to compare the clinical characteristics of tinnitus between patients from March to April 2020 under pandemic pressure and those from the matching period in 2019. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) questionnaire and the minimum masking level (MML) measure while anxiety was quantified using the Zung Self-rating Anxiety Scale (SAS). The assessments were repeated after a 2-month interval, in which sound therapy was applied to a subgroup of patients. In all, 94 and 70 cases were reported in the 2020 and 2019 groups, respectively. The effects of the pandemic on emotional status were evident from a higher incidence of anxiety and much higher SAS scores in the 2020 group. There was also an increase in the THI scores in the 2020 group, but the between-year difference was smaller than that of the SAS score. Moreover, there was no between-year difference in MML or the treatment effect, as measured via both THI and MML. Furthermore, the reduction in SAS score in the second assessment was significantly smaller in the 2020 group. However, a positive correlation between the initial SAS score and the improvement was seen within the 2020 group. Conclusions Anxiety increased greatly in tinnitus subjects due to the COVID 19 pandemic. However, this was not associated with an increase in tinnitus severity in 2020. Instead, there was no between-year difference in the THI score or MML or in the improvement of either measure after treatment. The smaller improvement in SAS score and the positive correlation with the initial SAS score in the 2020 group suggests that the SAS score change in this group might largely be due to the natural relief of pressure as the pandemic decelerated in China. Therefore, the anxiety change induced by the COVID 19 pandemic is not likely to have a strong impact on tinnitus.", "qid": 44, "docid": "k5r39gpe", "rank": 66, "score": 9.098099708557129}, {"content": "Title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus Content: A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for con- trolling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by Rc), is less than unity. This equilibrium is globally-asymptotically stable, for a special case of the model where quarantined-susceptible individuals do not acquire COVID-19 infection during quarantine, when Rc is less than unity. The epidemiological consequence of this theoretical result is that, the community-wide implementation of control interventions that can bring (and maintain) Rc to a value less than unity will lead to the effective control (or elimination) of COVID-19 in the community. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on baseline levels of interventions) are 105, 100 for New York state and 164, 000 for the entire US by the end of the pandemic. These numbers dramatically decreased by 80% and 64%, respectively, if adherence to strict social-distancing measures is improved and maintained until the end of May or June. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distance measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy \u2265 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.", "qid": 44, "docid": "yp8x5zwi", "rank": 67, "score": 9.067000389099121}, {"content": "Title: Preventing Facial Pressure Injury for Health Care Providers Adhering to COVID-19 Personal Protective Equipment Requirements Content: OBJECTIVE: To determine if a repurposed silicone-based dressing used underneath a N95 mask is a safe and beneficial option for facial skin injury prevention without compromising the mask's seal. METHODS: Since February 21, 2020, staff in high risk areas such as the ED and ICU of King Hamad University Hospital have worn N95 masks when doing aerosol-generating procedures to protect against the novel coronavirus 2019. At that time, without education enablers or resources that could be directly translated into practice, the hospital's Pressure Injury Prevention Committee explored and created a stepwise process to protect the skin under these masks. This procedure was developed over time and tested to make sure that it did not interfere with the effectiveness of the N95 mask seal. RESULTS: Skin protection was achieved by repurposing a readily available silicone border dressing cut into strips. This was tested on 10 volunteer staff members of various skin types and both sexes who became part of this evidence generation project. Oxygen saturation values taken before and after the 4-hour wear test confirmed that well-fitted facial protection did not compromise the mask seal, but rather improved it. An added advantage was increased comfort with less friction as self-reported by the staff. An educational enabler to prevent MDRPI from N95 mask wear was an important additional resource for the staff. CONCLUSIONS: This creative and novel stepwise process of developing a safe skin protection method by which staff could apply a repurposed silicone border dressing beneath an N95 mask was largely effective and aided by the creation of the enabler.", "qid": 44, "docid": "dozkil5p", "rank": 68, "score": 8.98330020904541}, {"content": "Title: Preventing Facial Pressure Injury for Health Care Providers Adhering to COVID-19 Personal Protective Equipment Requirements Content: OBJECTIVE: To determine if a repurposed silicone-based dressing used underneath a N95 mask is a safe and beneficial option for facial skin injury prevention without compromising the mask\u2019s seal. METHODS: Since February 21, 2020, staff in high risk areas such as the ED and ICU of King Hamad University Hospital have worn N95 masks when doing aerosol-generating procedures to protect against the novel coronavirus 2019. At that time, without education enablers or resources that could be directly translated into practice, the hospital\u2019s Pressure Injury Prevention Committee explored and created a stepwise process to protect the skin under these masks. This procedure was developed over time and tested to make sure that it did not interfere with the effectiveness of the N95 mask seal. RESULTS: Skin protection was achieved by repurposing a readily available silicone border dressing cut into strips. This was tested on 10 volunteer staff members of various skin types and both sexes who became part of this evidence generation project. Oxygen saturation values taken before and after the 4-hour wear test confirmed that well-fitted facial protection did not compromise the mask seal, but rather improved it. An added advantage was increased comfort with less friction as self-reported by the staff. An educational enabler to prevent MDRPI from N95 mask wear was an important additional resource for the staff. CONCLUSIONS: This creative and novel stepwise process of developing a safe skin protection method by which staff could apply a repurposed silicone border dressing beneath an N95 mask was largely effective and aided by the creation of the enabler.", "qid": 44, "docid": "l68ewxar", "rank": 69, "score": 8.983299255371094}, {"content": "Title: Network model and analysis of the spread of Covid-19 with social distancing Content: The first mitigation response to the Covid-19 pandemic was to limit person-to-person interaction as much as possible. This was implemented by the temporary closing of many workplaces and people were required to follow social distancing. Networks are a great way to represent interactions among people and the temporary severing of these interactions. Here, we present a network model of human-human interactions that could be mediators of disease spread. The nodes of this network are individuals and different types of edges denote family cliques, workplace interactions, interactions arising from essential needs, and social interactions. Each individual can be in one of four states: susceptible, infected, immune, and dead. The network and the disease parameters are informed by the existing literature on Covid-19. Using this model, we simulate the spread of an infectious disease in the presence of various mitigation scenarios. For example, lockdown is implemented by deleting edges that denote non-essential interactions. We validate the simulation results with the real data by matching the basic and effective reproduction numbers during different phases of the spread. We also simulate different possibilities of the slow lifting of the lockdown by varying the transmission rate as facilities are slowly opened but people follow prevention measures like wearing masks etc. We make predictions on the probability and intensity of a second wave of infection in each of these scenarios.", "qid": 44, "docid": "yat5g2i9", "rank": 70, "score": 8.976699829101562}, {"content": "Title: Widespread use of face masks in public may slow the spread of SARS CoV-2: an ecological study Content: Background The reasons for the large differences between countries in the sizes of their SARS CoV2 epidemics is unknown. Individual level studies have found that the use of face masks was protective for the acquisition and transmission of a range of respiratory viruses including SARS CoV1. We hypothesized that population level usage of face masks may be negatively associated SARS CoV2 spread. Methods At a country level, linear regression was used to assess the association between COVID19 diagnoses per inhabitant and the national promotion of face masks in public (coded as a binary variable), controlling for the age of the COVID19 epidemic and testing intensity. Results Eight of the 49 countries with available data advocated wearing face masks in public: China, Czechia, Hong Kong, Japan, Singapore, South Korea, Thailand and Malaysia. In multivariate analysis face mask use was negatively associated with number of COVID19 cases/inhabitant (coef. -326, 95% CI -601- -51, P=0.021). Testing intensity was positively associated with COVID-19 cases (coef. 0.07, 95% CI 0.05-0.08, P<0.001). Conclusion Whilst these results are susceptible to residual confounding, they do provide ecological level support to the individual level studies that found face mask usage to reduce the transmission and acquisition of respiratory viral infections.", "qid": 44, "docid": "5wsj003j", "rank": 71, "score": 8.972399711608887}, {"content": "Title: How should be the Surgical Treatment Approach during the COVID-19 Pandemic in Patients with Gastrointestinal Cancer? Content: COVID-19 was first seen in China at the end of December 2019. COVID-19 is a novel type of coronavirus that is defined as SARS-CoV-2, which can be mild or severe in the lungs, causing acute respiratory infection. The disease was first presented in the literature as Coronavirus Disease 2019 (COVID-19) in February 2020. The disease spread rapidly and was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. There have been approximately 7734185 reported cases, and 412369 reported deaths to date (09/June/2020). As COVID-19 spread in the world and our country, hospitals struggling with this disease have also become risky areas for transmitting the disease. Health workers also have a high risk of viral contamination from direct contact of droplets and surfaces. Personal protective equipment (PPE), such as masks, coveralls, gloves, face shields and/or goggles, are mandatory. The aim is to spread the flow of cases requiring hospitalization over time, thereby preventing possible accumulation in hospitals. All non-urgent procedures, such as elective surgeries and diagnostic interventions, were significantly affected. The hospitalization procedures were mostly allocated to patients with COVID-19 infection, and surgical operations were postponed. Only urgent surgical cases and oncological surgeries that cannot be postponed were performed during this pandemic process. Patients followed by oncology are immunosuppressed both because of the disease itself and the side effects of chemotherapy and/or radiotherapy taken. This makes patients more susceptible to infections, and the prognosis of infections in these patients is worse and more destructive. Cancer patients are almost twice as likely to catch COVID-19 compared to the general population. The choice of surgical procedures and perioperative management of the patients with malignancy has become even more important in the COVID-19 pandemic. In this study, we analyzed the treatment processes of our patients with malignancy that underwent a surgical oncological procedure during this pandemic.", "qid": 44, "docid": "0a371595", "rank": 72, "score": 8.964500427246094}, {"content": "Title: How Efficacious Must a COVID-19 Coronavirus Vaccine be to Prevent or Stop an Epidemic by Itself Content: Background: Given the continuing coronavirus disease 2019 (COVID-19) pandemic and much of the U.S. implementing social distancing due to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing. Methods: In 2020, we developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination. Results: Simulation experiments revealed that when vaccine efficacy exceeded 70%, coverage exceeded 60%, and vaccination occurred on day 1, the attack rate dropped to 22% with daily cases not exceeding 3.2 million (reproductive rate, R0, 2.5). When R0 was 3.5, the attack rate dropped to 41% with daily cases not exceeding 14.4 million. Increasing coverage to 75% when vaccination occurred by day 90 resulted in 5% attack rate and daily cases not exceeding 258,029when R0 was 2.5 and a 26% attack rate and maximum daily cases of 22.6 million when R0 was 3.5. When vaccination did not occur until day 180, coverage (i.e., those vaccinated plus those otherwise immune) had to reach 100%. A vaccine with an efficacy between 40% and 70% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages. Conclusion: Our study found that to either prevent or largely extinguish an epidemic without any other measures (e.g., social distancing), the vaccine has to have an efficacy of at least 70%.", "qid": 44, "docid": "tstx42h7", "rank": 73, "score": 8.963500022888184}, {"content": "Title: \"How much do young Italians know about COVID-19 and what are their attitudes towards the Sars-CoV-2? Results of a cross-sectional study\". Content: BACKGROUND At the end of 2019, an outbreak of novel coronavirus pneumonia, called Sars-CoV-2, was first identified in Wuhan, Hubei province, China. It subsequently spread throughout China and elsewhere, becoming a global health emergency. In February 2020, WHO designated the disease COVID-19. OBJECTIVE To investigate the degree of knowledge of young Italians about COVID-19 and their current attitudes towards the Sars-CoV-2 and to determine if there were prejudices emerging toward Chinese. METHODS An online survey was conducted on 3rd-4th-5th February 2020 with the collaboration of Italian Website \"Skuola.net\". Young people had the opportunity to participate by answering an ad hoc questionnaire created to investigate knowledge and attitudes about the new Coronavirus, using a link published on the Homepage. RESULTS 5234 responses were received of which 3262 were females and 1972 were males. Most of the participants showed generally moderate knowledge about COVID-19. Male students, middle school students and those who do not attend school, should increase awareness of the disease; less than half of responders say that their attitudes towards the Chinese population has worsened in the last period. CONCLUSIONS Global awareness of this emerging infection should be increased, due to its virulence, the significant risk of mortality and the ability of the virus to spread very quickly within the community.", "qid": 44, "docid": "tfums7or", "rank": 74, "score": 8.943599700927734}, {"content": "Title: \"How much do young Italians know about COVID-19 and what are their attitudes towards the Sars-CoV-2? Results of a cross-sectional study\" Content: BACKGROUND: At the end of 2019, an outbreak of novel coronavirus pneumonia, called Sars-CoV-2, was first identified in Wuhan, Hubei province, China. It subsequently spread throughout China and elsewhere, becoming a global health emergency. In February 2020, WHO designated the disease COVID-19. OBJECTIVE: To investigate the degree of knowledge of young Italians about COVID-19 and their current attitudes towards the Sars-CoV-2 and to determine if there were prejudices emerging toward Chinese. METHODS: An online survey was conducted on 3rd-4th-5th February 2020 with the collaboration of Italian Website \"Skuola.net\". Young people had the opportunity to participate by answering an ad hoc questionnaire created to investigate knowledge and attitudes about the new Coronavirus, using a link published on the Homepage. RESULTS: 5234 responses were received of which 3262 were females and 1972 were males. Most of the participants showed generally moderate knowledge about COVID-19. Male students, middle school students and those who do not attend school, should increase awareness of the disease; less than half of responders say that their attitudes towards the Chinese population has worsened in the last period. CONCLUSIONS: Global awareness of this emerging infection should be increased, due to its virulence, the significant risk of mortality and the ability of the virus to spread very quickly within the community.", "qid": 44, "docid": "ybvhhwkq", "rank": 75, "score": 8.943598747253418}, {"content": "Title: What Should I Do? Content: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.", "qid": 44, "docid": "idhr2upe", "rank": 76, "score": 8.927800178527832}, {"content": "Title: The effect of opening up the US on COVID-19 spread Content: In response to the pandemic development of the novel coronavirus (SARS-CoV-2), governments worldwide have implemented strategies of suppression by non-pharmaceutical interventions (NPIs). Such NPIs include social distancing, school closures, limiting international travel and complete lockdown. Worldwide the NPIs enforced to limit the spread of COVID-19 are now being lifted. Understanding how the risk increases when NPIs are lifted is important for decision making. Treating NPIs equally across countries and regions limits the possibility for modelling differences in epidemic response, as the response to the NPIs influences can vary between regions and this can affect the epidemic outcome, so do the strength and speed of lifting these. Our solution to this is to measure mobility changes from mobile phone data and their impacts on the basic reproductive number. We model the epidemic in all US states to compare the difference in outcome if NPIs are lifted or retained. We show that keeping NPIs just a few weeks longer has a substantial impact on the epidemic outcome.", "qid": 44, "docid": "7ogc51kf", "rank": 77, "score": 8.9173002243042}, {"content": "Title: A simple model to show the relative risk of viral aerosol infection and the benefit of wearing masks in different settings with implications for Covid-19 . Content: Background . Widespread use of masks in the general population is being used in many countries for Covid-19 . There has been reluctance on the part of the WHO and some governments to recommend this . Methodology . A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the benefit from use of masks which is multiplicative . Results . Social distancing at 2 metres is validated but in confined areas is time limited and the use of masks in the absence of extremely good ventilation is important. Where social distancing is not possible at all times or an infectious person is in a confined area for a prolonged period there is a higher risk of infection requiring protection . Conclusions . The use of masks should be factored into models and used at an early stage as widespread use of more efficient masks could have a large impact on control and spread of infection . Public health planning requires stockpiling masks and encouraging everyone to have suitable masks in their household when supplies are normalised . The use of a cloth mask will be better than no protection at all .", "qid": 44, "docid": "sqr11fpv", "rank": 78, "score": 8.907500267028809}, {"content": "Title: Impact of virus testing on COVID-19 case fatality rate: estimate using a fixed-effects model Content: Background In response to the SARS-CoV2 pandemic, governments have adopted a variety of public health measures. There are variations in how much testing has been done across countries. South Korea, Germany, and Iceland take the bet of massive testing of their population. Whereas tests were not performed widely in southern European countries. As the former undergo a lower case-fatality rate due to the COVID-19 than the latter, the impact of the testing strategy must be investigated. In this study, we aimed to evaluate the impact of testing on the case fatality rate. Methods We use data on inpatients across French geographic areas and propose a novel methodology that exploits policy discontinuities at region borders to estimate the effect of COVID-19 tests on the case-fatality rate. In France, testing policies are determined locally. We compare all contiguous department pairs located on the opposite sides of a region border. The heterogeneity in testing rate between department pairs together with the similarities in other dimensions allow us to mimic the existence of treatment and control groups and to identify the impact of testing on mortality. Results The increase of one percentage point in the test rate is associated with a decrease of 0.001 percentage point in the death rate. In other words, for each additional 1000 tests, one person would have remained alive. Conclusion Massive population testing could have a significant effect on mortality in different ways. Mass testing may help decision-makers to implement healthcare measures to limit the spread of the disease.", "qid": 44, "docid": "0l4pec0z", "rank": 79, "score": 8.89799976348877}, {"content": "Title: Preparedness and Response to COVID-19 in Saudi Arabia: Building on MERS Experience Content: Abstract Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.", "qid": 44, "docid": "tl3l0crr", "rank": 80, "score": 8.868499755859375}, {"content": "Title: Preparedness and response to COVID-19 in Saudi Arabia: Building on MERS experience Content: Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.", "qid": 44, "docid": "zntwsah4", "rank": 81, "score": 8.868498802185059}, {"content": "Title: Sense of community responsibility at the forefront of crisis management Content: The COVID-19 pandemic has made it clear that a sense of community responsibility is crucial to mitigate the effects of viral spread. Many citizens across the world have heeded the call to isolate and self-distance, yet large numbers of individuals do not seem to understand their responsibility for others. This article explores how a sense of community responsibility is born in community contexts, how various features of a crisis impact community responsibility, and how public administration plays a crucial role in facilitating mitigation and solutions to crisis. The article also explores the utility of the Community Experience Model in crisis management contexts, and sets the stage for further exploration of community experiences in disaster and crisis scholarship and practice.", "qid": 44, "docid": "nimh39bx", "rank": 82, "score": 8.868497848510742}, {"content": "Title: The Economic Costs of Containing a Pandemic Content: The coronavirus disease (COVID-19) has caused one of the most serious social and economic losses to countries around the world since the Spanish influenza pandemic of 1918 (during World War I). It has resulted in enormous economic as well as social costs, such as increased deaths from the spread of infection in a region. This is because public regulations imposed by national and local governments to deter the spread of infection inevitably involves a deliberate suppression of the level of economic activity. Given this trade-off between economic activity and epidemic prevention, governments should execute public interventions to minimize social and economic losses from the pandemic. A major problem regarding the resultant economic losses is that it unequally impacts certain strata of the society. This raises an important question on how such economic losses should be shared equally across the society. At the same time, there is some antipathy towards economic compensation by means of public debt, which is likely to increase economic burden in the future. However, as Paul Samuelson once argued, much of the burden, whether due to public debt or otherwise, can only be borne by the present generation, and not by future generations.", "qid": 44, "docid": "jyg9y4g2", "rank": 83, "score": 8.867899894714355}, {"content": "Title: What Should I Do? Content: OBJECTIVE: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? SUMMARY BACKGROUND DATA: Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. METHODS: In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. CONCLUSION: The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.", "qid": 44, "docid": "o01w28gb", "rank": 84, "score": 8.856499671936035}, {"content": "Title: Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S Content: This paper evaluates the dynamic impact of various policies adopted by US states on the growth rates of confirmed Covid-19 cases and deaths as well as social distancing behavior measured by Google Mobility Reports, where we take into consideration people's voluntarily behavioral response to new information of transmission risks. Our analysis finds that both policies and information on transmission risks are important determinants of Covid-19 cases and deaths and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments suggest that nationally mandating face masks for employees on April 1st could have reduced the growth rate of cases and deaths by more than 10 percentage points in late April, and could have led to as much as 17 to 55 percent less deaths nationally by the end of May, which roughly translates into 17 to 55 thousand saved lives. Our estimates imply that removing non-essential business closures (while maintaining school closures, restrictions on movie theaters and restaurants) could have led to -20 to 60 percent more cases and deaths by the end of May. We also find that, without stay-at-home orders, cases would have been larger by 25 to 170 percent, which implies that 0.5 to 3.4 million more Americans could have been infected if stay-at-home orders had not been implemented. Finally, not having implemented any policies could have led to at least a 7 fold increase with an uninformative upper bound in cases (and deaths) by the end of May in the US, with considerable uncertainty over the effects of school closures, which had little cross-sectional variation.", "qid": 44, "docid": "2zkesall", "rank": 85, "score": 8.854399681091309}, {"content": "Title: COVID-19: Present and Future Challenges for Dental Practice Content: COVID-19 was declared a pandemic by the World Health Organization, with a high fatality rate that may reach 8%. The disease is caused by SARS-CoV-2 which is one of the coronaviruses. Realizing the severity of outcomes associated with this disease and its high rate of transmission, dentists were instructed by regulatory authorities, such as the American Dental Association, to stop providing treatment to dental patients except those who have emergency complaints. This was mainly for protection of dental healthcare personnel, their families, contacts, and their patients from the transmission of virus, and also to preserve the much-needed supplies of personal protective equipment (PPE). Dentists at all times should competently follow cross-infection control protocols, but particularly during this critical time, they should do their best to decide on the emergency cases that are indicated for dental treatment. Dentists should also be updated on how this pandemic is related to their profession in order to be well oriented and prepared. This overview will address several issues concerned with the COVID-19 pandemic that directly relate to dental practice in terms of prevention, treatment, and orofacial clinical manifestations.", "qid": 44, "docid": "lt67jwyv", "rank": 86, "score": 8.83180046081543}, {"content": "Title: Understanding the Impact of Face Mask Usage Through Epidemic Simulation of Large Social Networks Content: Evidence from the 2003 SARS epidemic and 2009 H1N1 pandemic shows that face masks can be an effective non-pharmaceutical intervention in minimizing the spread of airborne viruses. Recent studies have shown that using face masks is correlated to an individual\u2019s age and gender, where females and older adults are more likely to wear a mask than males or youths. There are only a few studies quantifying the impact of using face masks to slow the spread of an epidemic at the population level, and even fewer studies that model their impact in a population where the use of face masks depends upon the age and gender of the population. We use a state-of-the-art agent-based simulation to model the use of face masks and quantify their impact on three levels of an influenza epidemic and compare different mitigation scenarios. These scenarios involve changing the demographics of mask usage, the adoption of mask usage in relation to a perceived threat level, and the combination of masks with other non-pharmaceutical interventions such as hand washing and social distancing. Our results shows that face masks alone have limited impact on the spread of influenza. However, when face masks are combined with other interventions such as hand sanitizer, they can be more effective. We also observe that monitoring social internet systems can be a useful technique to measure compliance. We conclude that educating the public on the effectiveness of masks to increase compliance can reduce morbidity and mortality.", "qid": 44, "docid": "14x4uqq7", "rank": 87, "score": 8.819600105285645}, {"content": "Title: Estimating a breakpoint in the spread pattern of COVID-19 in South Korea Content: OBJECTIVES: Amid the global COVID-19 crisis, South Korea has been touted for successfully preventing the spread of the infectious disease, which may be due to the aggressive implementation of preventive policies. We evaluated the spread pattern of COVID-19 in South Korea considering the potential impact of policy interventions on transmission rates. METHODS: The SIR (Susceptible-Infected-Removed) model with a breakpoint that allows a change in transmission rate at an unknown point was proposed. Estimated trajectories of COVID-19 from SIR models with and without a breakpoint were compared. RESULTS: The proposed model with a break fitted the actual series of infection case much better than the classic model. The estimated breakpoint was March 7(th) and the transmission rate dropped by 0.23 after the breakpoint. A counterfactual study based on our estimate indicated that the number of the infected could reach 2,500,000 compared to the peak of 8,000 in the observed series. CONCLUSIONS: It is critical to consider a change in the transmission rate to evaluate the spread trajectory of COVID-19 in South Korea. Our estimation and counterfactual experiments indicate that public health interventions may play a role in determining the spread pattern of infectious diseases.", "qid": 44, "docid": "lb0on0hi", "rank": 88, "score": 8.813300132751465}, {"content": "Title: Understanding the spreading patterns of COVID-19 in UK and its impact on exit strategies Content: Prior to lockdown the spread of COVID-19 in UK is found to be exponential, with an exponent 0.207. In case of COVID-19 this spreading behaviour is quantitatively better described with a mobility-driven SIR-SEIR model [2] rather than the homogenous mixing models. Lockdown has dramatically slowed down the spread of COVID-19 in UK, and even more significantly, has changed the growth in the total number of infected from exponential to quadratic. This significant change is due to a transition from a mobility-driven epidemic spreading to a spatial epidemic which is dominated by slow growth of spatially isolated clusters of infected population. Our results strongly indicate that, to avoid a return to exponential growth of COVID-19 (also known as second wave), mobility restrictions should not be prematurely lifted. Instead mobility should be kept restricted while new measures, such as wearing of masks and contact tracing, get implemented in order to prevent health services becoming overwhelmed due to a resurgence of exponential growth.", "qid": 44, "docid": "1oth8r7g", "rank": 89, "score": 8.802599906921387}, {"content": "Title: Protecting Labor and Delivery Personnel from COVID-19 during the Second Stage of Labor Content: The novel coronavirus disease 2019 (COVID-19) is spreading fast and is affecting the clinical workers at much higher risk than the general population. Little is known about COVID-19 effect on pregnant women; however, the emerging evidence suggests they may be at high risk of asymptomatic disease. In light of projected shortage of personal protective equipment (PPE), there is an aggressive attempt at conservation. In obstetrics, the guidelines on PPE use are controversial and differ among hospitals, globally, as well as nationally. The centers for disease control and prevention (CDC) recommend using N95 respirators, which are respirators that offer a higher level of protection instead of a facemask for when performing or present for an aerosol-generating procedures (AGP). However, the second stage of labor is not considered an AGP. The second stage of labor can last up to 4 hours. During that time, labor and delivery personnel is in close contact to patients, who are exerting extreme effort during and frequently blow out their breath, cough, shout, and vomit, all of which put the health care team at risk, considering that COVID-19 transmission occurs through aerosol generated by coughing and sneezing. The CDC and the American College of Obstetricians and Gynecologists (ACOG) do not provide clarification on the use of N95 during the second stage. We recommend that labor and delivery personnel have the utmost caution and be granted the protection they need to protect themselves and other patients. This includes providing labor and delivery personnel full PPE including N95 for the second stage of labor. This is critical to ensure the adequate protection for health care workers and to prevent spread to other health care workers and patients. Key Points: Second stage of labor exposes providers to aerosol. COVID-19 risk during second stage of labor is high. N95 should be used during second stage of labor.", "qid": 44, "docid": "i19v85o9", "rank": 90, "score": 8.770000457763672}, {"content": "Title: Protecting Labor and Delivery Personnel from COVID-19 during the Second Stage of Labor Content: The novel coronavirus disease 2019 (COVID-19) is spreading fast and is affecting the clinical workers at much higher risk than the general population. Little is known about COVID-19 effect on pregnant women; however, the emerging evidence suggests they may be at high risk of asymptomatic disease. In light of projected shortage of personal protective equipment (PPE), there is an aggressive attempt at conservation. In obstetrics, the guidelines on PPE use are controversial and differ among hospitals, globally, as well as nationally. The centers for disease control and prevention (CDC) recommend using N95 respirators, which are respirators that offer a higher level of protection instead of a facemask for when performing or present for an aerosol-generating procedures (AGP). However, the second stage of labor is not considered an AGP. The second stage of labor can last up to 4 hours. During that time, labor and delivery personnel is in close contact to patients, who are exerting extreme effort during and frequently blow out their breath, cough, shout, and vomit, all of which put the health care team at risk, considering that COVID-19 transmission occurs through aerosol generated by coughing and sneezing. The CDC and the American College of Obstetricians and Gynecologists (ACOG) do not provide clarification on the use of N95 during the second stage. We recommend that labor and delivery personnel have the utmost caution and be granted the protection they need to protect themselves and other patients. This includes providing labor and delivery personnel full PPE including N95 for the second stage of labor. This is critical to ensure the adequate protection for health care workers and to prevent spread to other health care workers and patients. KEY POINTS: \u00b7 Second stage of labor exposes providers to aerosol.. \u00b7 COVID-19 risk during second stage of labor is high.. \u00b7 N95 should be used during second stage of labor..", "qid": 44, "docid": "mplf3dz5", "rank": 91, "score": 8.769999504089355}, {"content": "Title: The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review. Content: Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "qid": 44, "docid": "f7rcijh4", "rank": 92, "score": 8.744199752807617}, {"content": "Title: Impact of Rumors and Misinformation on COVID-19 in Social Media Content: The coronavirus disease 2019 (COVID-19) pandemic has not only caused significant challenges for health systems all over the globe but also fueled the surge of numerous rumors, hoaxes, and misinformation, regarding the etiology, outcomes, prevention, and cure of the disease. Such spread of misinformation is masking healthy behaviors and promoting erroneous practices that increase the spread of the virus and ultimately result in poor physical and mental health outcomes among individuals. Myriad incidents of mishaps caused by these rumors have been reported globally. To address this issue, the frontline healthcare providers should be equipped with the most recent research findings and accurate information. The mass media, healthcare organization, community-based organizations, and other important stakeholders should build strategic partnerships and launch common platforms for disseminating authentic public health messages. Also, advanced technologies like natural language processing or data mining approaches should be applied in the detection and removal of online content with no scientific basis from all social media platforms. Furthermore, these practices should be controlled with regulatory and law enforcement measures alongside ensuring telemedicine-based services providing accurate information on COVID-19.", "qid": 44, "docid": "n8jobjm0", "rank": 93, "score": 8.731599807739258}, {"content": "Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.", "qid": 44, "docid": "svo94kuo", "rank": 94, "score": 8.72439956665039}, {"content": "Title: COVID-19: Special Precautions in Ophthalmic Practice and FAQs on Personal Protection and Mask Selection Content: The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory coronavirus-2, was first reported in December 2019. The World Health Organization declared COVID-19 a pandemic on March 11, 2020 and as of April 17, 2020, 210 countries are affected with >2,000,000 infected and 140,000 deaths. The estimated case fatality rate is around 6.7%. We need to step up our infection control measures immediately or else it may be too late to contain or control the spread of COVID-19. In case of local outbreaks, the risk of infection to healthcare workers and patients is high. Ophthalmic practice carries some unique risks and therefore high vigilance and special precautions are needed. We share our protocols and experiences in the prevention of infection in the current COVID-19 outbreak and the previous severe acute respiratory syndrome epidemic in Hong Kong. We also endeavor to answer the key frequently asked questions in areas of the coronaviruses, COVID-19, disease transmission, personal protection, mask selection, and special measures in ophthalmic practices. COVID-19 is highly infectious and could be life-threatening. Using our protocol and measures, we have achieved zero infection in our ophthalmic practices in Hong Kong and China. Preventing spread of COVID-19 is possible and achievable.", "qid": 44, "docid": "zxl84e2m", "rank": 95, "score": 8.723699569702148}, {"content": "Title: Adolescents\u2019 face mask usage and contact transmission in novel Coronavirus Content: The global outbreak of coronavirus has become an international public health threat. Prevention is of paramount importance to contain its spread. This study observes face mask wearing behavior and contact transmission problems in Taiwan. Teachers track student status in class. In addition to measuring body temperature and regular disinfection, classrooms require ventilation wear mask, provide alcohol spray and avoid sharing the microphone. Both questionnaire surveys and experimental were utilized. A total of 160 adults residing in Taiwan participated in the survey. The dye simulated the possible virus area on the mask surface during usage. Subjects were required to complete a questionnaire and simulate the spread of contact transmission when using a computer. Eighty-one % of respondents reported consistent use of surgical masks several times a day. They reported taking their masks off in relatively safe areas. Most people reported using one mask per day and storing the masks in their pockets. As a result, masks surface become a contamination source. In the contact experiment, ten adults were requested to don and doff a surgical mask while doing a word processing task. The extended contamination areas were recorded and identified by image analysis. The results show an average contamination area of the workspace is significant 530 cm(2). When the hand touches the surface of the mask, it may spread the virus to the subsequent contact area.", "qid": 44, "docid": "clidl6v1", "rank": 96, "score": 8.722100257873535}, {"content": "Title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China Content: There is currently a global outbreak of coronavirus disease 2019 (COVID-19), and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported.Describe the epidemic characteristics of COVID-19 in Jingmen, Hubei, introduce the local prevention and control experience, and observe the impact of various prevention and control measures on the number of new cases.All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29, 2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic.Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range, 2-88 years; IQR, 35-60). Thirty-three severe patients with a median age of 66 years (range, 33-82 years, IQR, 57-76) were treated in intensive care units; out of these patients, 66.7% (22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures.In conclusion, all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious, control measures have proven to be very effective, particularly wearing masks, which could prevent most infections.", "qid": 44, "docid": "ei0lagpp", "rank": 97, "score": 8.691100120544434}, {"content": "Title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China Content: There is currently a global outbreak of coronavirus disease 2019 (COVID-19), and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported. Describe the epidemic characteristics of COVID-19 in Jingmen, Hubei, introduce the local prevention and control experience, and observe the impact of various prevention and control measures on the number of new cases. All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29, 2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic. Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range, 2\u201388 years; IQR, 35\u201360). Thirty-three severe patients with a median age of 66 years (range, 33\u201382 years, IQR, 57\u201376) were treated in intensive care units; out of these patients, 66.7% (22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures. In conclusion, all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious, control measures have proven to be very effective, particularly wearing masks, which could prevent most infections.", "qid": 44, "docid": "kbxlo7pu", "rank": 98, "score": 8.691099166870117}, {"content": "Title: Silk fabric as a protective barrier for personal protective equipment and as a functional material for face coverings during the COVID-19 pandemic Content: Background The worldwide shortage of single-use N95 respirators and surgical masks due to the COVID-19 pandemic has forced many health care personnel to prolong the use of their existing equipment as much as possible. In many cases, workers cover respirators with available masks in an attempt to extend their effectiveness against the virus. Due to low mask supplies, many people instead are using face coverings improvised from common fabrics. Our goal was to determine what fabrics would be most effective in both practices. Methods and findings We examined the hydrophobicity of fabrics (silk, cotton, polyester), as measured by their resistance to the penetration of small and aerosolized water droplets, an important transmission avenue for the virus causing COVID-19. We also examined the breathability of these fabrics and their ability to maintain hydrophobicity despite undergoing repeated cleaning. Tests were done when fabrics were fashioned as an overlaying barrier and also when constructed as do-it-yourself face coverings. As a protective barrier and face covering, silk is more effective at impeding the penetration and absorption of droplets due to its greater hydrophobicity relative to other tested fabrics. Silk face coverings repelled droplets as well as masks, but unlike masks they are hydrophobic and can be readily sterilized for immediate reuse. Conclusions Silk is an effective hydrophobic barrier to droplets, more breathable than other fabrics that trap humidity, and are readily re-useable via cleaning. Therefore, silk can serve as an effective material for protecting respirators under clinical conditions and as a material for face coverings.", "qid": 44, "docid": "akffx93g", "rank": 99, "score": 8.688899993896484}, {"content": "Title: An exploration of how fake news is taking over social media and putting public health at risk. Content: Recent statistics show that almost 1/4 of a million people have died and four million people are affected either with mild or serious health problems caused by coronavirus (COVID-19). These numbers are rapidly increasing (World Health Organization, May 3, 2020c). There is much concern during this pandemic about the spread of misleading or inaccurate information. This article reports on a small study which attempted to identify the types and sources of COVID-19 misinformation. The authors identified and analysed 1225 pieces of COVID-19 fake news stories taken from fact-checkers, myth-busters and COVID-19 dashboards. The study is significant given the concern raised by the WHO Director-General that 'we are not just fighting the pandemic, we are also fighting infodemic'. The study concludes that the COVID-19 infodemic is full of false claims, half backed conspiracy theories and pseudoscientific therapies, regarding the diagnosis, treatment, prevention, origin and spread of the virus. Fake news is pervasive in social media, putting public health at risk. The scale of the crisis and ubiquity of the misleading information require that scientists, health information professionals and journalists exercise their professional responsibility to help the general public identify fake news stories. They should ensure that accurate information is published and disseminated.J.M.", "qid": 44, "docid": "518e2x3h", "rank": 100, "score": 8.680700302124023}]}
{"query": "How has the COVID-19 pandemic impacted mental health?", "hits": [{"content": "Title: Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff Content: Purpose: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. Methods: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. Results: 2,180 staff from a range of sectors, professions and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. Conclusion: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.", "qid": 45, "docid": "mfetvz49", "rank": 1, "score": 12.191800117492676}, {"content": "Title: \u201cI feel like death on legs\u201d: COVID-19 isolation and mental health Content: Abstract This study investigates the personal and collective responses to COVID-19, as it is described in personal stories and newspaper reports and examines the social and economic impact of the pandemic on different societies. Although some studies have been done on the impact of COVID-19, these studies focus on epidemiology, the importance of language diversity and reflections on the pandemic. None of the studies so far have focused specifically on the impact the coronavirus has had on different societies because of the global lockdown and restrictions on people\u2019s movements. This study attempts to address this gap in the literature by focusing on how the language used in personal stories and newspaper reports reveal the impact of COVID-19 on different societies by investigating how self-isolation and lockdown measures is leading to mental health breakdown in individuals and affecting wider social and economic collapse. Prior literature (Gortner and Pennebaker, 2003) suggests that the media generally parallel society\u2019s psychological response to traumatic events making newspapers an important collective resource similar to personal stories. The scale of the pandemic is such that it has been likened to a situation of war. In this climate, where the response to the pandemic is analogous to fighting a war, it was interesting to see what effect the enforced lockdown has on people\u2019s mental health well-being and what priorities the media focus on. Smith, Anderson-Hanley, Langrock, and Compas (2005) have shown that language use in descriptions of traumatic experiences can shed insight into successful and unsuccessful coping strategies. I have therefore chosen to look at two different countries, Sri Lanka and Britain in order to investigate the following research questions: (1) Is self-isolation due to COVID-19 having an effect on mental health in Britain? And (2) What are the priorities of different countries during the crisis as evident in newspaper reports? To answer these two research questions, I have collected a small corpus of personal stories from Britain and two small corpora of newspaper reports from Britain and Sri Lanka over a span of one month. The data was analysed using corpus linguistics methodology such as keyword analysis of the two newspaper reports using AntConc (Anthony, 2019) and the personal stories were analysed using Linguistic Inquiry and Word Count (LIWC) (Pennebaker, 2015). The findings from LIWC shows that the enforced self-isolation is leading to mental health breakdown but that there are also positive emotions of the desire to help and solidarity with others. The analysis of the news reports show that Britain\u2019s priorities are centered on the government\u2019s handling of the crisis and the economy whereas Sri Lankan newspapers focus on educating people about the dangers of COVID-19.", "qid": 45, "docid": "w5u4zxdb", "rank": 2, "score": 12.109999656677246}, {"content": "Title: Mental Health and the COVID19 Pandemic. Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 45, "docid": "hze88sr4", "rank": 3, "score": 12.041600227355957}, {"content": "Title: Mental Health and the COVID19 Pandemic Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 45, "docid": "wbwd7m5w", "rank": 4, "score": 12.04159927368164}, {"content": "Title: The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study Content: BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people\u2019s mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.", "qid": 45, "docid": "8r0orhkm", "rank": 5, "score": 11.73550033569336}, {"content": "Title: The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study Content: BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people's mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.", "qid": 45, "docid": "fjss4e92", "rank": 6, "score": 11.735499382019043}, {"content": "Title: Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts Content: Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.", "qid": 45, "docid": "a3lk2q02", "rank": 7, "score": 11.617799758911133}, {"content": "Title: COVID-19 Implications on Clinical Clerkships and the Residency Application Process for Medical Students Content: The coronavirus disease 2019 (COVID-19) pandemic has caused significant disruption to undergraduate medical education (UME). Although the immediate scheduling challenges are being addressed, there has been less discourse regarding how this pandemic will impact medical students in their preparation for and application to residency programs. While some historical disasters and pandemics provide a loose precedent for UME response during COVID-19, the impact of the current pandemic has surpassed any other events. COVID-19 will likely impact UME in the suspension of clinical rotations, alterations in grading, suspension or elimination of away rotations, changes in medical licensing exams, and ramifications on mental health. This review assesses governing medical bodies\u2019 recommendations regarding UME during the COVID-19 pandemic and how this may impact preparation for residency. In particular, residency programs will likely have to create new guidelines for assessing applicants during this unique cycle.", "qid": 45, "docid": "w8xv6l7m", "rank": 8, "score": 11.508600234985352}, {"content": "Title: COVID-19 Pandemic: Impact on psychiatric care in the United States Content: The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of \"how to\" processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.", "qid": 45, "docid": "nxqa2wis", "rank": 9, "score": 11.507100105285645}, {"content": "Title: COVID-19 Pandemic: Impact on Psychiatric Care in the United States, a Review Content: Abstract The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of \u201chow to\u201d processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.", "qid": 45, "docid": "td9syerz", "rank": 10, "score": 11.507099151611328}, {"content": "Title: Mental health and capacity laws in Northern Ireland and the COVID-19 pandemic: Examining powers, procedures and protections under emergency legislation Content: This article examines the changes made to mental health and capacity laws in Northern Ireland through temporary emergency legislation, known as the Coronavirus Act 2020. The purpose of the legislation was to respond to the emergency situation created by the COVID-19 pandemic, in particular the increase pressure placed on health services in the United Kingdom. An overview is provided of the government's rationale for the changes to Northern Ireland mental health and capacity laws, as well as exploring how they are likely to be operationalised in practice. Consideration is also given as to how such changes may impact upon existing human rights protections for persons assessed as lacking mental capacity. It is argued that it is important that regular parliamentary oversight is maintained in relation to the potential impact and consequences of such changes during the period they are in force. This should be done in order to assess whether they remain a necessary, proportionate and least restrictive response to the challenges faced in managing mental health and capacity issues in Northern Ireland during this public health emergency.", "qid": 45, "docid": "ma27v97d", "rank": 11, "score": 11.346699714660645}, {"content": "Title: COVID-19 related stress exacerbates common physical and mental pathologies and affects treatment (Review) Content: COVID-19 pandemic has caused a global public health emergency resulting in unprecedented individual and societal fear and anxiety. The stress surrounding this biothreat appears to have clinical implications in all aspects of medicine, both in mental and physical health spheres. The impact of COVID-19 related anxiety in Cardiology, Paediatrics, Oncology, Dermatology, Neurology and Mental Health and how it affects treatments is discussed. Moreover, the need for introducing novel communication and therapeutic approaches is highlighted in the new landscape of the COVID-19 era.", "qid": 45, "docid": "j7novgyb", "rank": 12, "score": 11.337400436401367}, {"content": "Title: Trajectories of depression and anxiety during enforced isolation due to COVID-19: longitudinal analyses of 59,318 adults in the UK with and without diagnosed mental illness Content: Background: There is currently major concern about the impact of the global COVID-19 outbreak on mental health. A number of studies suggest that mental health deteriorated in many countries prior to enforced isolation (lockdown), but it remains unknown how mental health has changed during lockdown. Aims: This study explored trajectories of anxiety and depression over the first two months of lockdown using data from the UK, and compared the experiences of individuals with and without diagnosed mental illness. Methods: Data from 53,328 adults in the UCL COVID -19 Social Study (a well-stratified panel study weighted to population proportions collecting data weekly during the Covid-19 pandemic) were analysed from 21/03/2020-10/05/2020. Growth curve modelling was fitted accounting for socio-demographic and health covariates. Results: 24.4% of the sample had scores indicating moderate-severe anxiety, and 31.4% indicating moderate-severe depressive symptoms. Over the first two months of lockdown, there was only a slight decrease in anxiety levels amongst participants as a whole and a very small decrease in depression levels between weeks 3-6 that then increased again in weeks 7-8. Adults with pre-existing diagnoses of mental health conditions had higher levels of anxiety and depression but there was no evidence of widening inequalities in mental health experiences compared to people without existing mental illness. Conclusions: Results suggest there has been little improvement in depression and only slight improvements in anxiety since lockdown commenced in the UK. These findings suggest greater efforts need to be made to help individuals manage their mental health during the pandemic.", "qid": 45, "docid": "3gxgruuo", "rank": 13, "score": 11.303999900817871}, {"content": "Title: The Impact of Quarantine and Physical Distancing Following COVID-19 on Mental Health: Study Protocol of a Multicentric Italian Population Trial Content: The COVID-19 pandemic and its related containment measures\u2014mainly physical distancing and isolation\u2014are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The \u201cCOVID-IT-mental health trial\u201d is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1\u2014COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2\u2014COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3\u2014COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4\u2014COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups.", "qid": 45, "docid": "vl5zhxyh", "rank": 14, "score": 11.24020004272461}, {"content": "Title: Dimensions and modulators of behavioural and mental-health changes during the Covid-19 pandemic: an N=343,017 study Content: BACKGROUND The effects of the Covid-19 pandemic on mental health remain unclear. To mitigate the risks and capitalise on opportunities for positive change, we must understand how the impact has been mediated by sociodemographics, mental disorders, personality traits, life circumstances and the coping measures people choose to take. METHODS Data were collected from 376,987 members of the general public, predominantly in the UK, between late December 2019 and May 2020. Interaction models examined differences in sociodemographic distributions of mood and anxiety for 233,268 people in January vs. 109,749 in May. Factor analysis of a comprehensive instrument determined the dimensionality of self-perceived pandemic-driven change in wellbeing, outlook and behaviour for 74,830 participants in May. Linear modelling identified demographic, contextual, clinical, and trait predictors of pandemic impact. Topic modelling distilled prevalent advice from free-text responses. RESULTS Anxiety, depression and insomnia changed markedly in demographically-mediated ways. Untoward changes were larger for older adults. Benefits were greater for younger adults. Social connectedness was negatively affected across most mental and neurological conditions. There were disorder-specific changes in other domains, e.g., heightened conflict at home for attention-deficit hyperactivity disorder and heightened anxiety for obsessive-compulsive disorder. Psychiatric symptoms, personality traits, occupational variables and living conditions were amongst the strongest predictors of pandemic impact. Frontline health workers, carers of vulnerable older adults, and disabled or sheltered adults were disproportionately affected. Fifty advice topics were identified from free-text, the prevalence of which covaried with subpopulation, context and traits. CONCLUSIONS The general public report positive and negative consequences of the pandemic. Particular subsets of people have heightened risk of untoward effects whereas other groups appear resilient. To be valid and effective, studies seeking to quantify, predict or mitigate the impact of pandemics on mental health should apply holistic approaches, combining multiple psycho-socio-economic factors.", "qid": 45, "docid": "oxs7qc0f", "rank": 15, "score": 11.235300064086914}, {"content": "Title: 'Drawing on Wisdom to Cope with Adversity:' A Systematic Review Protocol of Older Adults' Mental and Psychosocial Health During Acute Respiratory Disease Propagated-Type Epidemics and Pandemics (COVID-19, SARS-CoV, MERS, and Influenza). Content: Background: Mental health has become one of the fundamental priorities during the COVID-19 pandemic. Situations like physical distancing as well as being constantly tagged as the most vulnerable group could expose older adults to mental and psychosocial burdens. Nonetheless, there is little clarity about the impact of the COVID-19 pandemic or similar pandemics in the past on the mental illness, wellbeing, and psychosocial health of the older population compared to other age groups. Objectives: To describe the patterns of older adults' mental and psychosocial health related to acute respiratory disease propagated-type epidemics and pandemics and to evaluate the differences with how other age groups respond. Eligibility criteria: quantitative and qualitative studies evaluating mental illness, wellbeing, or psychosocial health outcomes associated with respiratory propagated epidemics and pandemics exposure or periods (COVID-19, SARS-CoV, MERS, and Influenza) in people 65 years or older. Data source: Original articles published until June 1st, 2020, in any language searched in the electronic healthcare and social sciences database: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, WHO Global literature on coronavirus disease database, China National Knowledge Infrastructure ( - CNKI). Furthermore, EPPI Centre's COVID-19 living systematic map and the publicly available publication list of the COVID-19 living systematic review will be incorporated for preprints and recent COVID-19 publications. Data extraction: Two independent reviewers will extract predefined parameters. The risk of bias will be assessed. Data synthesis: Data synthesis will be performed according to study type and design, type of epidemic and pandemic, types of outcomes (mental health and psychosocial outcomes), and participant characteristics (e.g., sex, race, age, socioeconomic status, food security, presence of dependency in daily life activities independent/dependent older adults). Comparison between sex, race, and other age groups will be performed qualitatively, and quantitatively if enough data is available. The risk of bias and study heterogeneity will be reported for quantitative studies. Conclusion: This study will provide information to take actions to address potential mental health difficulties during the COVID-19 pandemic in older adults and to understand responses on this age group. Furthermore, it will be useful to identify potential groups that are more vulnerable or resilient to the mental-health challenges of the current worldwide pandemic.", "qid": 45, "docid": "7950xjmv", "rank": 16, "score": 11.224499702453613}, {"content": "Title: The impact of the COVID-19 pandemic on suicide rates Content: Multiple lines of evidence indicate that the COVID-19 pandemic has profound psychological and social effects. The psychological sequelae of the pandemic will probably persist for months and years to come. Studies indicate that the COVID-19 pandemic is associated with distress, anxiety, fear of contagion, depression, and insomnia in the general population and among health care professionals. Social isolation, anxiety, fear of contagion, uncertainty, chronic stress, and economic difficulties may lead to the development or exacerbation of depressive, anxiety, substance use, and other psychiatric disorders in vulnerable populations including individuals with pre-existing psychiatric disorders and people who reside in high COVID-19 prevalence areas. Stress-related psychiatric conditions including mood and substance use disorders are associated with suicidal behavior. COVID-19 survivors may also be at elevated suicide risk. The COVID-19 crisis may increase suicide rates during and after the pandemic. Mental health consequences of the COVID-19 crisis including suicidal behavior are likely to be present for a long time and peak later than the actual pandemic. To reduce suicides during the COVID-19 crisis it is imperative to decrease stress, anxiety, fears and loneliness in the general population. There should be traditional and social media campaigns to promote mental health and reduce distress. Active outreach is necessary, especially for people with a history of psychiatric disorders, COVID-19 survivors, and older adults. Research studies are needed of how mental health consequences can be mitigated during and after the COVID-19 pandemic.", "qid": 45, "docid": "y9vx7coj", "rank": 17, "score": 11.182900428771973}, {"content": "Title: Nurses' Mental Health and Well-Being: COVID-19 Impacts Content: The editorial will introduce a special section on nurses' mental health and well-being that will showcase results from a groundbreaking pan-Canadian study of nurses' occupational stress. The article series highlights research efforts toward better supporting nurses' mental health. In this editorial, we discuss the importance of this research in light of the COVID-19 pandemic. We review the current stressors faced by nurses and anticipate how nurses' mental health and well-being will be impacted by COVID-19.", "qid": 45, "docid": "f6c7e0e4", "rank": 18, "score": 11.168499946594238}, {"content": "Title: Nurses' Mental Health and Well-Being: COVID-19 Impacts. Content: The editorial will introduce a special section on nurses' mental health and well-being that will showcase results from a groundbreaking pan-Canadian study of nurses' occupational stress. The article series highlights research efforts toward better supporting nurses' mental health. In this editorial, we discuss the importance of this research in light of the COVID-19 pandemic. We review the current stressors faced by nurses and anticipate how nurses' mental health and well-being will be impacted by COVID-19.", "qid": 45, "docid": "tj3lmjx3", "rank": 19, "score": 11.168498992919922}, {"content": "Title: Rising Tide: Responding to the Mental Health Impact of the COVID\u201019 Pandemic Content: Now freely downloadable on the Anxiety and Depression Association of America website (https://adaa.org/sites/default/files/PhasedApproachtoCovid\u201019.ver1.1%20(002).pdf) is a framework for COVID\u201019 mental health response (see Table 1). This framework of phased interventions and resources is intended to assist health systems and programs impacted by the pandemic to plan for how to address current mental health issues arising as well as to prepare and plan for the continued needs of their communities, patients, and staff. This article is protected by copyright. All rights reserved.", "qid": 45, "docid": "jcueu1xh", "rank": 20, "score": 11.106200218200684}, {"content": "Title: Impact of COVID-19 on gaming disorder: Monitoring and prevention. Content: The global coronavirus disease 2019 (COVID-19) outbreak has necessitated physical distancing, lockdown, contact tracing, and self-quarantine so as to prevent the spread of the disease. Amid the outbreak, gaming data usage has reportedly increased in the United States, and game download volume has reached a record high in Europe. Because gaming can be used to cope with the psychological stress from the outbreak, therefore mental health professionals should be aware of how increased gaming during the pandemic may contribute to risk of gaming disorder, especially if the pandemic persists. Mental health professionals should thus formulate safe social interaction alternatives for people, particularly adolescents, who have gaming disorder risk.", "qid": 45, "docid": "6j8y4d1l", "rank": 21, "score": 10.993300437927246}, {"content": "Title: Impact of COVID-19 on gaming disorder: Monitoring and prevention Content: The global coronavirus disease 2019 (COVID-19) outbreak has necessitated physical distancing, lockdown, contact tracing, and self-quarantine so as to prevent the spread of the disease. Amid the outbreak, gaming data usage has reportedly increased in the United States, and game download volume has reached a record high in Europe. Because gaming can be used to cope with the psychological stress from the outbreak, therefore mental health professionals should be aware of how increased gaming during the pandemic may contribute to risk of gaming disorder, especially if the pandemic persists. Mental health professionals should thus formulate safe social interaction alternatives for people, particularly adolescents, who have gaming disorder risk.", "qid": 45, "docid": "k5nn7p39", "rank": 22, "score": 10.99329948425293}, {"content": "Title: \u201cIt's about how much we can do, and not how little we can get away with\u201d: Coronavirus-related legislative changes for social care in the United Kingdom Content: The coronavirus pandemic, referred to here as Covid-19, has brought into sharp focus the increasing divergence of devolved legislation and its implementation in the United Kingdom. One such instance is the emergency health and social care legislation and guidance introduced by the United Kingdom Central Government and the devolved Governments of Wales, Scotland and Northern Ireland in response to this pandemic. We provide a summary, comparison and discussion of these proposed and actual changes with a particular focus on the impact on adult social care and safeguarding of the rights of citizens. To begin, a summary and comparison of the relevant changes, or potential changes, to mental health, mental capacity and adult social care law across the four jurisdictions is provided. Next, we critique the suggested and actual changes and in so doing consider the immediate and longer term implications for adult social care, including mental health and mental capacity, at the time of publication.several core themes emerged: concerns around process and scrutiny; concerns about possible changes to the workforce and last, the possible threat on the ability to safeguard human rights. It has been shown that, ordinarily, legislative provisions across the jurisdictions of the UK are different, save for Wales (which shares most of its mental health law provisions with England). Such divergence is also mirrored in the way in which the suggested emergency changes could be implemented. Aside from this, there is also a wider concern about a lack of parity of esteem between social care and health care, a concern which is common to all. What is interesting is that the introduction of CVA 2020 forced a comparison to be made between the four UK nations which also shines a spotlight on how citizens can anticipate receipt of services.", "qid": 45, "docid": "zlaqcem1", "rank": 23, "score": 10.987299919128418}, {"content": "Title: COVID\u201019 under the SARS Cloud: Mental Health Nursing during the Pandemic in Hong Kong Content: This editorial presents a commentary on COVID-19 and mental health in Hong Kong. We outline the current measures being used to contain the outbreak and how the experience of the SARS epidemic may have influenced the response in Hong Kong. We also discuss the potential mental health ill-effects of the pandemic and its impact on mental health nursing locally.", "qid": 45, "docid": "nd4f7b6s", "rank": 24, "score": 10.97819995880127}, {"content": "Title: Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement from the Cardiac Society of Australia and New Zealand (CSANZ) # Content: Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. Challenges The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. Recommendations Every effort should be made to deliver safe ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.", "qid": 45, "docid": "bc7q8swu", "rank": 25, "score": 10.975199699401855}, {"content": "Title: Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement from the Cardiac Society of Australia and New Zealand (CSANZ) Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. CHALLENGES: The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. RECOMMENDATIONS: Every effort should be made to deliver safe, ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.", "qid": 45, "docid": "vxw4dvnb", "rank": 26, "score": 10.975198745727539}, {"content": "Title: Rapid report: Early demand, profiles and concerns of mental health users during the coronavirus (COVID-19) pandemic Content: BACKGROUND: Trends in contact with a high volume national digital mental health service (DMHS), the MindSpot Clinic, provide a unique opportunity to assess the mental health effects of the COVID-19 pandemic. METHODS: Three methods were used to assess changes in responses to COVID-19. First, website visits and call centre traffic were compared across two time periods: the \u201ccomparison period\u201d (1 September 2020 to 28 September 2019), and during the early weeks of the \u201cCOVID-19 pandemic\u201d (19 March 2020 to 15 April 2020). Second, demographic and symptom data were compared across all patients who started an assessment during the comparison (n = 1650) and the COVID-19 period (n = 1668). Third, responses to questions about the impact of COVID-19 introduced to the assessment from 19 March 2020, and reports from treating therapists were examined. RESULTS: There was an 89% increase in website visits and a 90% increase in telephone calls to the clinic in the early COVID-19 period compared to the comparison period. There was a higher proportion of females in the COVID-19 sample (76.9% vs. 72.9), and a lower proportion reported being in employment (52.8% vs. 60.8%). There was a small but significant increase in the severity of anxiety symptoms, and an increase in the number of people reporting recent onset of anxiety and depression. However, there were no differences between groups in severity of symptoms of distress or depression. Most people (94%) reported concern about the impact of COVID-19, and 88% reported making changes in lifestyle. Older adults had higher levels of concern about COVID-19. Therapists reported that patients were concerned about how to access testing, manage quarantine, financial security and the effect of social isolation. CONCLUSIONS: COVID-19 has resulted in a significant increase in contact with an established DMHS, but we have not yet detected increases in baseline symptom severity. With the prospect of prolonged restriction of movement, DMHS such as MindSpot could play an important role in both providing clinical services and monitoring the mental health of the population.", "qid": 45, "docid": "4ec9n4d0", "rank": 27, "score": 10.96030044555664}, {"content": "Title: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Content: The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.", "qid": 45, "docid": "d8aa0ro1", "rank": 28, "score": 10.924599647521973}, {"content": "Title: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Content: Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.", "qid": 45, "docid": "knlc3bxh", "rank": 29, "score": 10.924598693847656}, {"content": "Title: Adjustment and coronavirus: How to prepare for COVID-19 pandemic-related adjustment disorder worldwide? Content: As the 2019 novel coronavirus (COVID-19) is spreading worldwide in 2020, there is a growing concern about the impact of the pandemic on mental health. Multiple stressors associated with the pandemic, such as health-related stressors, job loss, and work-related stressors, could increase the prevalence of adjustment disorders worldwide. The present article acknowledges adjustment disorder as a highly relevant mental health outcome of the pandemic that should be addressed by mental health professionals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "3yikeq42", "rank": 30, "score": 10.847700119018555}, {"content": "Title: COVID-19 pandemic: mental health and beyond - The Indian perspective Content: India is a de facto continent in the garb of a country. COVID-19 is an unprecedented global pandemic spanning continents. Being the second most populous country in the world, experts regard how India deals with the outbreak will have enormous impact on the world's ability to deal with it. The country has been in lockdown since 25th March 2020 until the current time of early May 2020, and despite several challenges there has been early success. The major conflict now is the health benefits weighed up against the deleterious social and economic consequences of prolonged lockdown i.e. life versus livelihood. This unprecedented calamity could potentially cause or exacerbate various psychiatric disorders. It is recognised that lifestyle changes and limited screen time may help reduce mental health difficulties. Considering the physical barriers to consultation, development of telemedicine services is needed. This pandemic, like other previous pandemics, will pass and until this happens we must remain extremely vigilant.", "qid": 45, "docid": "ex5unvr8", "rank": 31, "score": 10.845800399780273}, {"content": "Title: COVID-19 pandemic: mental health and beyond - The Indian perspective. Content: India is a de facto continent in the garb of a country. COVID-19 is an unprecedented global pandemic spanning continents. Being the second most populous country in the world, experts regard how India deals with the outbreak will have enormous impact on the world's ability to deal with it. The country has been in lockdown since 25th March 2020 until the current time of early May 2020, and despite several challenges there has been early success. The major conflict now is the health benefits weighed up against the deleterious social and economic consequences of prolonged lockdown i.e. life versus livelihood. This unprecedented calamity could potentially cause or exacerbate various psychiatric disorders. It is recognised that lifestyle changes and limited screen time may help reduce mental health difficulties. Considering the physical barriers to consultation, development of telemedicine services is needed. This pandemic, like other previous pandemics, will pass and until this happens we must remain extremely vigilant.", "qid": 45, "docid": "u46upe5l", "rank": 32, "score": 10.845799446105957}, {"content": "Title: The scope of mental health research during the COVID-19 pandemic and its aftermath Content: The effects of the COVID-19 pandemic on population mental health are unknown. We need to understand the scale of any such impact in different sections of the population, who is most affected and how best to mitigate, prevent and treat any excess morbidity. We propose a coordinated and interdisciplinary mental health science response.", "qid": 45, "docid": "ilk9u1a8", "rank": 33, "score": 10.842499732971191}, {"content": "Title: Expressive Interviewing: A Conversational System for Coping with COVID-19 Content: The ongoing COVID-19 pandemic has raised concerns for many regarding personal and public health implications, financial security and economic stability. Alongside many other unprecedented challenges, there are increasing concerns over social isolation and mental health. We introduce \\textit{Expressive Interviewing}--an interview-style conversational system that draws on ideas from motivational interviewing and expressive writing. Expressive Interviewing seeks to encourage users to express their thoughts and feelings through writing by asking them questions about how COVID-19 has impacted their lives. We present relevant aspects of the system's design and implementation as well as quantitative and qualitative analyses of user interactions with the system. In addition, we conduct a comparative evaluation with a general purpose dialogue system for mental health that shows our system potential in helping users to cope with COVID-19 issues.", "qid": 45, "docid": "rhcvsqtk", "rank": 34, "score": 10.79580020904541}, {"content": "Title: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses Content: The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "hlbjrkqp", "rank": 35, "score": 10.779399871826172}, {"content": "Title: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses. Content: The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "q1ywk5vc", "rank": 36, "score": 10.779398918151855}, {"content": "Title: Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19 Content: OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems.", "qid": 45, "docid": "yyux8k36", "rank": 37, "score": 10.727299690246582}, {"content": "Title: Covid-19, child and adolescent mental health \u2013 Croatian (in)experience Content: The Covid-19 pandemic has caused unseen socio-economic changes all over the world, where enormous efforts are being made to preserve lives and maintain functional health systems. A secondary concern is to mitigate the severe economic consequences of the crisis. Different approaches have been adopted with varying outcomes and experiences. But regardless of the different approaches taken, one thing is common for all societies during this pandemic: fear and anxiety. This fear extends from concerns about the present situation, for the health and well-being of family members and loved ones from Covid-19 infection, to fears relating to how long the crisis will last, to the potential economic consequences of the pandemic (perhaps not seen in our lifetimes) and the ultimate fear of future uncertainty. Across the world, health systems are being faced with unprecedented challenges. At their core, these challenges are the same: how to beat Covid-19. Certainly, there are differences in how individual systems are organized and how they address the main issues arising from the pandemic while not forgetting the ongoing healthcare needs of the general population. In this paper, we share some perspectives from Croatia regarding Child and Adolescent Mental Health services (CAMHs) in these extraordinary circumstances. We give our personal insights on deficiencies in Child and Adolescent Mental Health Services prior to the arrival of Covid-19, which have contributed to difficulties in mitigating and managing the ongoing crisis.", "qid": 45, "docid": "pqom76hk", "rank": 38, "score": 10.62339973449707}, {"content": "Title: Covid-19, child and adolescent mental health - Croatian (in)experience Content: The Covid-19 pandemic has caused unseen socio-economic changes all over the world, where enormous efforts are being made to preserve lives and maintain functional health systems. A secondary concern is to mitigate the severe economic consequences of the crisis. Different approaches have been adopted with varying outcomes and experiences. But regardless of the different approaches taken, one thing is common for all societies during this pandemic: fear and anxiety. This fear extends from concerns about the present situation, for the health and well-being of family members and loved ones from Covid-19 infection, to fears relating to how long the crisis will last, to the potential economic consequences of the pandemic (perhaps not seen in our lifetimes) and the ultimate fear of future uncertainty. Across the world, health systems are being faced with unprecedented challenges. At their core, these challenges are the same: how to beat Covid-19. Certainly, there are differences in how individual systems are organized and how they address the main issues arising from the pandemic while not forgetting the ongoing healthcare needs of the general population. In this paper, we share some perspectives from Croatia regarding Child and Adolescent Mental Health services (CAMHs) in these extraordinary circumstances. We give our personal insights on deficiencies in Child and Adolescent Mental Health Services prior to the arrival of Covid-19, which have contributed to difficulties in mitigating and managing the ongoing crisis.", "qid": 45, "docid": "wbl2hg7d", "rank": 39, "score": 10.623398780822754}, {"content": "Title: The mental health impact of the covid-19 pandemic onhealthcare workers, and interventions to help them: a rapid systematic review Content: Background: The covid-19 pandemic has heavily burdened, and in some cases overwhelmed, healthcare systems throughout the world. Healthcare workers are not only at heightened risk of infection, but also of adverse mental health outcomes. Identification of organizational, collegial and individual risk and resilience factors impacting the mental health of healthcare workers are needed to inform preparedness planning and sustainable response. Methods: We performed a rapid systematic review to identify, assess and summarize available research on the mental health impact of the covid-19 pandemic on healthcare workers. On 11 May 2020, we utilized the Norwegian Institute of Public Health's Live map of covid-19 evidence, the visualization of a database of 20,738 screened studies, to identify studies for inclusion. We included studies reporting on any type of mental health outcome in any type of healthcare workers during the pandemic. We described interventions reported by the studies, and narratively summarized mental health-related outcomes, as study heterogeneity precluded meta-analysis. We assessed study quality using design-specific instruments. Results: We included 59 studies, reporting on a total of 54,707 healthcare workers. The prevalence of general psychological distress across the studies ranged from 7-97% (median 37%), anxiety 9-90% (median 24%), depression 5-51% (median 21%), and sleeping problems 34-65% (median 37%). Seven studies reported on implementing mental health interventions, and most focused on individual symptom reduction, but none reported on effects of the interventions. In most studies, healthcare workers reported low interest in and use of professional help, and greater reliance on social support and contact with family and friends. Exposure to covid-19 was the most commonly reported correlate of mental health problems, followed by female gender, and worry about infection or about infecting others. Social support correlated with less mental health problems. Discussion: Healthcare workers in a variety of fields, positions, and exposure risks are reporting anxiety, depression, sleep problems, and distress during the covid-19 pandemic, but most studies do not report comparative data on mental health symptoms. before the pandemic. There seems to be a mismatch between risk factors for adverse mental health outcomes among healthcare workers in the current pandemic and their needs and preferences, and the individual psychopathology focus of current interventions. Efforts to help healthcare workers sustain healthy relationships to colleagues, family and friends over time may be paramount to safeguard what is already an important source of support during the prolonged crisis. Expanding interventions' focus to incorporate organizational, collegial and family factors to support healthcare workers responding to the pandemic could improve acceptability and efficacy of interventions. Other: The protocol for this review is available online. No funding was received.", "qid": 45, "docid": "23cjm86c", "rank": 40, "score": 10.61400032043457}, {"content": "Title: Impact of COVID-19 pandemic on mental health of young people and adults: a systematic review protocol of observational studies Content: INTRODUCTION: Since the WHO declared COVID-19 as a pandemic, the spread of the new coronavirus has been the focus of attention of scientists, governments and populations. One of the main concerns is the impact of this pandemic on health outcomes, mainly on mental health. Even though there are a few empirical studies on COVID-19 and mental health, so far, there is no systematic review about the impact of COVID-19 on mental health of young people and adults yet. We aim to critically synthesise the scientific evidence about the impact of the COVID-19 pandemic on the mental health of young people and adults. METHODS AND ANALYSIS: A systematic review will be performed through eight databases: MEDLINE (Medical Literature Analysis and Retrieval System Online), ISI-of-Knowledge, CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE (Excerpta Medica Database), SCOPUS, LILACS (Latin American and Caribbean Health Sciences Literature), PsycINFO (Psychology Information) and CNKI (Chinese National Knowledge Infrastructure), from inception until 30 June 2020. No restriction regarding the publication date, setting or languages will be considered. Preliminary search strategies were carried out on 29 March 2020 and will be updated in June 2020. The primary outcomes will be the prevalence and the severity of psychological symptoms in young people and adults (>18 years old) resulting from the impact of COVID-19 pandemic. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Pooled standardised mean differences and 95% CIs will be calculated. The risk of bias of the observational studies will be assessed through the Methodological Index for Non-Randomised Studies (MINORS). Additionally, if sufficient data are available, a meta-analysis will be conducted. Heterogeneity between the studies will be determined by the I(2) statistics. Subgroup analyses will also be performed. Publication bias will be checked with funnel plots and Egger\u2019s test. Heterogeneity will be explored by random-effects analysis. ETHICS AND DISSEMINATION: Ethical assessment was not required. Findings will be disseminated through peer-reviewed publication and will be presented at conferences related to this field. PROSPERO REGISTRATION NUMBER: CRD42020177366.", "qid": 45, "docid": "5h6d1obb", "rank": 41, "score": 10.58240032196045}, {"content": "Title: Impact of COVID-19 pandemic on mental health of young people and adults: a systematic review protocol of observational studies Content: INTRODUCTION: Since the WHO declared COVID-19 as a pandemic, the spread of the new coronavirus has been the focus of attention of scientists, governments and populations. One of the main concerns is the impact of this pandemic on health outcomes, mainly on mental health. Even though there are a few empirical studies on COVID-19 and mental health, so far, there is no systematic review about the impact of COVID-19 on mental health of young people and adults yet. We aim to critically synthesise the scientific evidence about the impact of the COVID-19 pandemic on the mental health of young people and adults. METHODS AND ANALYSIS: A systematic review will be performed through eight databases: MEDLINE (Medical Literature Analysis and Retrieval System Online), ISI-of-Knowledge, CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE (Excerpta Medica Database), SCOPUS, LILACS (Latin American and Caribbean Health Sciences Literature), PsycINFO (Psychology Information) and CNKI (Chinese National Knowledge Infrastructure), from inception until 30 June 2020. No restriction regarding the publication date, setting or languages will be considered. Preliminary search strategies were carried out on 29 March 2020 and will be updated in June 2020. The primary outcomes will be the prevalence and the severity of psychological symptoms in young people and adults (>18 years old) resulting from the impact of COVID-19 pandemic. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Pooled standardised mean differences and 95% CIs will be calculated. The risk of bias of the observational studies will be assessed through the Methodological Index for Non-Randomised Studies (MINORS). Additionally, if sufficient data are available, a meta-analysis will be conducted. Heterogeneity between the studies will be determined by the I2 statistics. Subgroup analyses will also be performed. Publication bias will be checked with funnel plots and Egger's test. Heterogeneity will be explored by random-effects analysis. ETHICS AND DISSEMINATION: Ethical assessment was not required. Findings will be disseminated through peer-reviewed publication and will be presented at conferences related to this field. PROSPERO REGISTRATION NUMBER: CRD42020177366.", "qid": 45, "docid": "78d5mlp2", "rank": 42, "score": 10.582399368286133}, {"content": "Title: Mental Health Problems during the COVID-19 Pandemics and the Mitigation Effects of Exercise: A Longitudinal Study of College Students in China Content: (1) Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. Vast resources have been allocated to control the pandemic and treat patients. However, little attention has been paid to the adverse impact on mental health or effective mitigation strategies to improve mental health. (2) Purpose: The aim of this study was to assess the adverse impact of the COVID-19 outbreak on Chinese college students\u2019 mental health, understand the underlying mechanisms, and explore feasible mitigation strategies. (3) Methods: During the peak time of the COVID-19 outbreak in China, we conducted longitudinal surveys of sixty-six college students. Structured questionnaires collected information on demographics, physical activity, negative emotions, sleep quality, and aggressiveness level. A mixed-effect model was used to evaluate associations between variables, and the mediating effect of sleep quality was further explored. A generalized additive model was used to determine the dose-response relationships between the COVID-19 death count, physical activity, and negative emotions. (4) Results: The COVID-19 death count showed a direct negative impact on general sleep quality (\u03b2 = 1.37, 95% confidence interval [95% CI]: 0.55, 2.19) and reduced aggressiveness (\u03b2 = \u22126.57, 95% CI: \u221212.78, \u22120.36). In contrast, the COVID-19 death count imposed not a direct but an indirect impact on general negative emotions (indirect effect (IE) = 0.81, p = 0.012), stress (IE = 0.40, p < 0.001), and anxiety (IE = 0.27, p = 0.004) with sleep quality as a mediator. Moreover, physical activity directly alleviated general negative emotions (\u03b2 = \u22120.12, 95% CI: \u22120.22, \u22120.01), and the maximal mitigation effect occurred when weekly physical activity was about 2500 METs. (5) Conclusions: (a) The severity of the COVID-19 outbreak has an indirect effect on negative emotions by affecting sleep quality. (b) A possible mitigation strategy for improving mental health includes taking suitable amounts of daily physical activity and sleeping well. (c) The COVID-19 outbreak has reduced people\u2019s aggressiveness, probably by making people realize the fragility and preciousness of life.", "qid": 45, "docid": "hp11at50", "rank": 43, "score": 10.504500389099121}, {"content": "Title: Mental Health Problems during the COVID-19 Pandemics and the Mitigation Effects of Exercise: A Longitudinal Study of College Students in China Content: (1) Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. Vast resources have been allocated to control the pandemic and treat patients. However, little attention has been paid to the adverse impact on mental health or effective mitigation strategies to improve mental health. (2) Purpose: The aim of this study was to assess the adverse impact of the COVID-19 outbreak on Chinese college students' mental health, understand the underlying mechanisms, and explore feasible mitigation strategies. (3) Methods: During the peak time of the COVID-19 outbreak in China, we conducted longitudinal surveys of sixty-six college students. Structured questionnaires collected information on demographics, physical activity, negative emotions, sleep quality, and aggressiveness level. A mixed-effect model was used to evaluate associations between variables, and the mediating effect of sleep quality was further explored. A generalized additive model was used to determine the dose-response relationships between the COVID-19 death count, physical activity, and negative emotions. (4) Results: The COVID-19 death count showed a direct negative impact on general sleep quality (\u00df = 1.37, 95% confidence interval [95% CI]: 0.55, 2.19) and reduced aggressiveness (\u00df = -6.57, 95% CI: -12.78, -0.36). In contrast, the COVID-19 death count imposed not a direct but an indirect impact on general negative emotions (indirect effect (IE) = 0.81, p = 0.012), stress (IE = 0.40, p < 0.001), and anxiety (IE = 0.27, p = 0.004) with sleep quality as a mediator. Moreover, physical activity directly alleviated general negative emotions (\u00df = -0.12, 95% CI: -0.22, -0.01), and the maximal mitigation effect occurred when weekly physical activity was about 2500 METs. (5) Conclusions: (a) The severity of the COVID-19 outbreak has an indirect effect on negative emotions by affecting sleep quality. (b) A possible mitigation strategy for improving mental health includes taking suitable amounts of daily physical activity and sleeping well.", "qid": 45, "docid": "37seijbr", "rank": 44, "score": 10.481499671936035}, {"content": "Title: Discussion of digital gaming's impact on players' well-being during the COVID-19 lockdown Content: This research discusses how to utilise digital gaming to support the well-being of its users and sustain their physical and mental health during the COVID-19 lockdown in which people's activities are limited. The published academic literature that is written in English and available for access on online databases was reviewed to develop key take-aways and a framework for discussing how to enhance people's well-being in the COVID-19 lockdown. Interaction with other players in virtual communities has been found to have a positive influence on the mental health of those suffering from a lack of societal connection. A framework for further research has also been developed that focuses on the critical situation of the COVID-19 lockdown,as this is an urgent topic with a huge impact on our health.Some gaming service providers have been proactive in redesigning game programming to be suitable for the lockdown situation, and this enables players to enjoy physical activities even at home.", "qid": 45, "docid": "idlabzms", "rank": 45, "score": 10.473400115966797}, {"content": "Title: Impact of the COVID-19 Pandemic on Adult Mental Health Content: The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.", "qid": 45, "docid": "880lwnde", "rank": 46, "score": 10.445899963378906}, {"content": "Title: Structuring mental health support for frontline caregivers during COVID-19: lessons from organisational scholarship on unit-aligned support Content: BACKGROUND: Although the COVID-19 pandemic exposes frontline caregivers to severe prolonged stresses and trauma, there has been little clarity on how healthcare organisations can structure support to address these mental health needs. This article translates organisational scholarship on professionals working in organisations to elucidate why traditional approaches to supporting employee mental health, which often ask employees to seek assistance from centralised resources that separate mental health personnel from frontline units, may be insufficient under crisis conditions. We identify a critical but often overlooked aspect of employee mental health support: how frontline professionals respond to mental health services. In high-risk, high-pressure fields, frontline professionals may perceive mental health support as coming at the expense of urgent frontline work goals (ie, patient care) and as clashing with their central professional identities (ie, as expert, self-reliant ironmen/women). FINDINGS: To address these pervasive goal and identity conflicts in professional organisations, we translate the results of a multiyear research study examining the US Army\u2019s efforts to transform its mental health support during the wars in Iraq and Afghanistan. We highlight parallels between providing support to frontline military units and frontline healthcare units during COVID-19 and surface implications for structuring mental health supports during a crisis. We describe how an intentional organisational design used by the US Army that assigned specific mental health personnel to frontline units helped to mitigate professional goal and identity conflicts by creating personalised relationships and contextualising mental health offerings. CONCLUSION: Addressing frontline caregivers\u2019 mental health needs is a vital part of health delivery organisations\u2019 response to COVID-19, but without thoughtful organisational design, well-intentioned efforts may fall short. An approach that assigns individual mental health personnel to support specific frontline units may be particularly promising.", "qid": 45, "docid": "r8teblhs", "rank": 47, "score": 10.401100158691406}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: BACKGROUND: The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. CHALLENGES: The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. PURPOSE: This commentary aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 45, "docid": "d7vo3l8e", "rank": 48, "score": 10.39210033416748}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: Background The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. Challenges The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. Purpose This statement aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 45, "docid": "pf1f9fhc", "rank": 49, "score": 10.392099380493164}, {"content": "Title: The effects of misleading media reports about COVID-19 on Chinese tourists\u2019 mental health: a perspective article Content: The novel coronavirus (COVID-19) has been declared apublic health emergency of international concern by the World Health Organization. This pandemic has since saturated the headlines of major international media channels that disseminate information to global citizens. However, some media coverage of COVID-19 has negatively influenced Chinese travellers\u2019 mental health due to the outbreak having been labelled \u201cChinese virus pandemonium.\u201d Key world leaders have also parroted such sensationalism; for example, President Donald Trump called COVID-19 the \u201cChinese virus\u201d. This discriminatory labelling has resulted in violent attacks on Chinese international travellers and students. This perspective article explores how misleading and discriminatory media reports may affect the mental well-being of ethnically Chinese travellers during the global COVID-19 pandemic.", "qid": 45, "docid": "7c72n11m", "rank": 50, "score": 10.372200012207031}, {"content": "Title: Healthcare workers experiences of working on the frontline and views about support during COVID-19 and comparable pandemics: A rapid review and meta-synthesis Content: Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline healthcare workers and growing calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers own perspectives or what their views are about support. This rapid review identified 40 qualitative studies which have explored healthcare workers experiences and views from previous pandemics, including and comparable to COVID-19. Meta-synthesis of this qualitative data using thematic analysis derived eight key themes which transcended pandemics, time, and geographical boundaries. This pandemic is not unprecedented; the themes that arose from previous pandemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of these previous pandemics, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.", "qid": 45, "docid": "6gc7smqf", "rank": 51, "score": 10.349900245666504}, {"content": "Title: The Lifelines COVID-19 Cohort: a questionnaire-based study to investigate COVID-19 infection and its health and societal impacts in a Dutch population-based cohort Content: The COVID-19 pandemic has affected billions of people around the world not only through the infection itself but also through its wider impact on public health and daily life. To assess the effects of the pandemic, a team of researchers across a wide range of disciplines developed and implemented the Lifelines COVID-19 questionnaire, leading to the development of the Lifelines COVID-19 cohort. This cohort is recruited from participants of the Lifelines prospective population cohort and the Lifelines NEXT birth cohort, and participants were asked to fill out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March of 2020 and on a bi-weekly basis staring in June 2020. The Lifelines region covers the three Northern provinces of the Netherlands-Drenthe, Groningen and Friesland-which together account for about 10% of the Dutch population. To date, >70,000 people have responded to the questionnaires at least once, and the questionnaire program is still ongoing. Data collected by the questionnaires will be used to address four aspects of the outbreak: (1) how the COVID-19 pandemic developed in the three northern provinces of the Netherlands, (2) which environmental risk factors predict disease susceptibility and severity, (3) which genetic risk factors predict disease susceptibility and severity and (4) what are the psychological and societal impacts of the crisis.", "qid": 45, "docid": "6w8jun1e", "rank": 52, "score": 10.347200393676758}, {"content": "Title: Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis Content: BACKGROUND: The COVID-19 pandemic has had a significant impact on public mental health. Therefore, monitoring and oversight of the population mental health during crises such as a panedmic is an immediate priority. The aim of this study is to analyze the existing research works and findings in relation to the prevalence of stress, anxiety and depression in the general population during the COVID-19 pandemic. METHOD: In this systematic review and meta-analysis, articles that have focused on stress and anxiety prevalence among the general population during the COVID-19 pandemic were searched in the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI) and Google Scholar databases, without a lower time limit and until May 2020. In order to perform a meta-analysis of the collected studies, the random effects model was used, and the heterogeneity of studies was investigated using the I(2) index. Moreover. data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. RESULTS: The prevalence of stress in 5 studies with a total sample size of 9074 is obtained as 29.6% (95% confidence limit: 24.3\u201335.4), the prevalence of anxiety in 17 studies with a sample size of 63,439 as 31.9% (95% confidence interval: 27.5\u201336.7), and the prevalence of depression in 14 studies with a sample size of 44,531 people as 33.7% (95% confidence interval: 27.5\u201340.6). CONCLUSION: COVID-19 not only causes physical health concerns but also results in a number of psychological disorders. The spread of the new coronavirus can impact the mental health of people in different communities. Thus, it is essential to preserve the mental health of individuals and to develop psychological interventions that can improve the mental health of vulnerable groups during the COVID-19 pandemic.", "qid": 45, "docid": "8ab8rugv", "rank": 53, "score": 10.28219985961914}, {"content": "Title: Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses Content: Purpose The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. Methods We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. Results We found 872 eligible sources from 29 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. Conclusion Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.", "qid": 45, "docid": "uyebygdm", "rank": 54, "score": 10.275899887084961}, {"content": "Title: Attitude, practice, behavior, and mental health impact of COVID-19 on doctors Content: Background: COVID-19, like every other pandemic, has imposed an unprecedented threat to doctors' physical and mental health. Literature in this area is sparse. The present study has been done to explore the knowledge, attitude, and behavior of doctors regarding this pandemic and how it influences their depression, anxiety, and stress level. Materials and Methods: This online survey has been done for 10 days. Data were collected on background characteristics, knowledge, attitude, and behavior of the respondents in a semi-structured pro forma, and psychiatric morbidity was measured by the Depression, Anxiety, and Stress Scale-21. A total of 152 complete responses have been received. The data were assessed using SPSS software. Results: Out of 152 study participants, 34.9% were depressed and 39.5% and 32.9% were having anxiety and stress, respectively. Significant predictors for psychiatric morbidities were experience in health sector, duty hours, use of protective measures, and altruistic coping. Multivariable logistic regression showed most of the factors to be significantly associated with depression, anxiety, and stress level. Discussion: Doctors who were working during COVID pandemic have a high prevalence of psychiatric morbidity. Age and having multiple comorbidities are significant predictive factors. Adequate protective measures should be warranted. Altruistic coping and a sense of greater goal are significant among the doctor community, in this pressing time. The doctors are pushing themselves to the best of their capacity and also protecting their patients' best interest. A large-scale, multicentric study will probably give a larger picture and will guide us for better service planning and delivery.", "qid": 45, "docid": "msc7pj0x", "rank": 55, "score": 10.27299976348877}, {"content": "Title: Prisons confin\u00e9es : quelles cons\u00e9quences pour les soins psychiatriques et la sant\u00e9 mentale des personnes d\u00e9tenues en France ?/ [Mental health care in French correctional facilities during the Covid-19 pandemic] Content: OBJECTIVE: The impact of the Covid-19 pandemic on the 11 million people currently incarcerated worldwide is the subject of many concerns. Prisons and jails are filled with people suffering from many preexisting medical conditions increasing the risk of complications. Detainees' access to medical services is already limited and overcrowding poses a threat of massive contagion. Beyond the health impact of the crisis, the tightening of prison conditions worries. On March 16, 2020, in France, the lockdown measures have been accompanied by specific provisions for prisons: all facilities have suspended visitations, group activities and external interventions. Over 10,000 prisoners have been released to reduce the prison population and the risk of virus propagation. These adjustments had major consequences on the healthcare system in French prisons. The objectives of this article are to describe the reorganization of the three levels of psychiatric care for inmates in France in the context of Covid-19 pandemic and to have a look at the impact of lockdown measures and early releases on mental health of prisoners. METHODS: This work is based on a survey conducted in April 2020 in France among psychiatric healthcare providers working in 42 ambulatory units for inmates and in the 9 full-time inpatient psychiatric wards exclusively for inmates called \"UHSAs\" (which stands for \"unit\u00e9s hospitali\u00e8res sp\u00e9cialement am\u00e9nag\u00e9es\", and can be translated as \"specially equipped hospital units\"). A review of the international literature on mental healthcare system for inmates during the Covid-19 epidemic has also been performed. RESULTS: The Covid-19 epidemic has been rather contained during the period of confinement in French prisons but the impact of confinement measures on the prison population is significant. The three levels of psychiatric care for inmates have implemented specific measures to ensure continuity of care, to support detainees during Coronavirus lockdown and to prevent an infection's spread. Among the most important are: limitation of medical consultations to serious and urgent cases, creation of \"Covid units\", cancellation of voluntary psychiatric hospitalizations, reinforcement of preventive hygiene measures and reshuffling of medical staff. Prolonged confinement has consequences on mental health of detainees. Currently, mental health workers are facing multiple clinical situations such as forced drug and substance withdrawal (linked to difficulties in supplying psychoactive substances), symptoms of anxiety (due to concerns for their own and their relatives' well-being) and decompensation among patients with severe psychiatric conditions. Early releases from prison may also raise some issues. People recently released from prison are identified as at high risk of death by suicide and drug overdose. The lack of time to provide the necessary link between health services within prisons and health structures outside could have serious consequences, emphasizing the well-known \"revolving prison doors\" effect. DISCUSSION: The current lockdown measures applied in French jails and prisons point out the disparities between psychiatric care for inmates and psychiatric care for general population. Giving the high vulnerability of prison population, public health authorities should pay more attention to health care in prisons.", "qid": 45, "docid": "74xuvaz6", "rank": 56, "score": 10.265199661254883}, {"content": "Title: \u2018Quit During COVID-19\u2019\u2014staying smokefree in mental health in-patient settings Content: Cigarette smoking is one of the main preventable causes of cancers globally. At this time of global emergency, mental health professionals all over the world are joining hands with the public health and other healthcare communities to focus on acute measures to save lives from COVID-19. This has been particularly challenging in mental health hospital settings where numerous additional factors need to be considered, including difficulties of implementing social distancing, potential impacts of social isolation, increased stress levels and implications of all this on smoking. In this article, we will briefly discuss the prevalence of smoking in mental health patients, especially in those in mental health hospital settings and also what is the possible impact of COVID-19 pandemic in these people. Then we will go through the main reasons as to why encouraging smoking cessation in mental health patients is so important and measures we can take for supporting mental health patients quit smoking even during COVID-19 times. The smoking cessation interventions have a direct bearing on preventing future cancers and achieving smoking cessation among cancer patients in this already disadvantaged group.", "qid": 45, "docid": "fgjzo4xq", "rank": 57, "score": 10.212599754333496}, {"content": "Title: Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic Content: BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain relevant expertise spanning NIBS technology, clinical services, and basic and clinical research \u2013 with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.", "qid": 45, "docid": "6wlq7syf", "rank": 58, "score": 10.200599670410156}, {"content": "Title: Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic Content: BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.", "qid": 45, "docid": "uan7leat", "rank": 59, "score": 10.20059871673584}, {"content": "Title: Special Ambulatory Gynecologic Considerations in the Era of COVID-19 and Implications for Future Practice. Content: The COVID-19 pandemic has altered medical practice in unprecedented ways. While much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain impacts of COVID-19 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care as well. In this article we review important ambulatory gynecologic topics including safety and metal health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible for how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns; threaten continued access to contraception and abortion services; impact prepregnancy planning; interrupt routine screening for breast and cervical cancer; increase risk of sexually-transmitted infection acquisition and decrease access to treatment; and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertion can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasound and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually-transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. While routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papilloma virus self-samples using new cervical cancer screening guidelines that can be expanded in light of the pandemic situation. While the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to attempt to improve health equity.", "qid": 45, "docid": "hlymyzcq", "rank": 60, "score": 10.190199851989746}, {"content": "Title: Feminism and gendered impact of COVID\u201019: Perspective of a counselling psychologist Content: When women, girls and gender\u2010diverse people \u2014 who have been disproportionately impacted by the COVID\u201019 pandemic outbreak since the public health crisis has also become a crisis for feminism \u2014 will identify and acknowledge their organismic phenomenological self, wholeness and growth will be fully functioning. Psychological aspects for the public health emergency operated through counselling psychologists to manage mental health, emotional, psychological, cognitive, behavioural, relational and social impacts are fundamental. And the role of counselling psychologists in maintaining personal mental health and their clients is a crucial indicator of collective wellbeing. This perspective is embedded in the gendered approach and feminist framework which attempts to explore and offer the embodied intersectional and divergent impact on living during the COVID\u201019 pandemic lockdown.", "qid": 45, "docid": "4laqdzui", "rank": 61, "score": 10.1673002243042}, {"content": "Title: How to Defend COVID-19 in Taiwan? Talk about People's Disease Awareness, Attitudes, Behaviors and the Impact of Physical and Mental Health Content: This study explored awareness, attitudes, and behavior in relation to Coronavirus Disease 2019 (COVID-19) prevention among Taiwanese citizens and their physical and mental health statuses. Through collection of 2132 questionnaire responses in field research, the present researchers analyzed the data using descriptive statistics and various approaches. In conclusion, the public's high level of willingness to share information, sufficient knowledge of and consensus on epidemic prevention between individuals and families, strict compliance with relevant regulations, effective preventive measures, and adequate public facilities have contributed to control of COVID-19. However, vigilance and awareness of the pandemic in some individuals, epidemic-prevention campaigns, and community-based preventive measures were insufficient. Some citizens subsequently suffered from headaches, anxiety, and mood instability. Furthermore, demographic variables (place of residence, sex, age, and occupation) and physical and mental health status produced various effects on citizens' awareness, attitude, and behavior regarding epidemic prevention as well as the perceived effect of COVID-19 on physical and mental health.", "qid": 45, "docid": "gv2owt9e", "rank": 62, "score": 10.167299270629883}, {"content": "Title: How to Defend COVID-19 in Taiwan? Talk about People's Disease Awareness, Attitudes, Behaviors and the Impact of Physical and Mental Health. Content: This study explored awareness, attitudes, and behavior in relation to Coronavirus Disease 2019 (COVID-19) prevention among Taiwanese citizens and their physical and mental health statuses. Through collection of 2132 questionnaire responses in field research, the present researchers analyzed the data using descriptive statistics and various approaches. In conclusion, the public's high level of willingness to share information, sufficient knowledge of and consensus on epidemic prevention between individuals and families, strict compliance with relevant regulations, effective preventive measures, and adequate public facilities have contributed to control of COVID-19. However, vigilance and awareness of the pandemic in some individuals, epidemic-prevention campaigns, and community-based preventive measures were insufficient. Some citizens subsequently suffered from headaches, anxiety, and mood instability. Furthermore, demographic variables (place of residence, sex, age, and occupation) and physical and mental health status produced various effects on citizens' awareness, attitude, and behavior regarding epidemic prevention as well as the perceived effect of COVID-19 on physical and mental health.", "qid": 45, "docid": "t9oh2i0t", "rank": 63, "score": 10.167298316955566}, {"content": "Title: Challenges and recommendations for mental health providers during the COVID-19 pandemic: the experience of China\u2019s First University-based mental health team Content: Coronavirus Disease is impacting the entire world. As the first country that has needed to confront this disease, China has responded with unprecedented and hugely successful public health initiatives. Almost simultaneous with the awareness of the potential for widespread loss of life, the first Chinese university recognizing the likely psychological impacts of COVID-19, assembled the first university-based professional team to offer pandemic-related mental health services to the Chinese public. This paper describes the work that we provided and the challenges encountered. The challenges are described in four contexts: the organizational/systemic level, the technical perspective, the therapeutic process, and the ethical aspects. We also provide recommendations on what we can do in the short term, and future improvements that can be made.", "qid": 45, "docid": "4qvv1hsq", "rank": 64, "score": 10.166099548339844}, {"content": "Title: Challenges and recommendations for mental health providers during the COVID-19 pandemic: the experience of China's First University-based mental health team Content: Coronavirus Disease is impacting the entire world. As the first country that has needed to confront this disease, China has responded with unprecedented and hugely successful public health initiatives. Almost simultaneous with the awareness of the potential for widespread loss of life, the first Chinese university recognizing the likely psychological impacts of COVID-19, assembled the first university-based professional team to offer pandemic-related mental health services to the Chinese public. This paper describes the work that we provided and the challenges encountered. The challenges are described in four contexts: the organizational/systemic level, the technical perspective, the therapeutic process, and the ethical aspects. We also provide recommendations on what we can do in the short term, and future improvements that can be made.", "qid": 45, "docid": "orfzsfo3", "rank": 65, "score": 10.166098594665527}, {"content": "Title: A population mental health perspective on the impact of COVID-19. Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "4q1j6g44", "rank": 66, "score": 10.162699699401855}, {"content": "Title: A population mental health perspective on the impact of COVID-19 Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "6ngsyo8o", "rank": 67, "score": 10.162698745727539}, {"content": "Title: Pediatric mental and behavioral health in the period of quarantine and social distancing (COVID-19) Content: UNSTRUCTURED: The COVID-19 pandemic has spread rapidly throughout the world and has generated a long-term impact. The pandemic has caused great harm to society and also caused serious psychological trauma to many people. Pediatrics are a vulnerable group in this global public health emergency, as their nervous systems, endocrine systems and hypothalamic-pituitary-adrenal axes are not well developed. Psychological crises often cause pediatrics to produce feelings of abandonment, despair, incapacity and exhaustion, and even raising the risk of suicide. Children with mental illnesses are especially vulnerable during the quarantine and social distancing period. The inclusion of psychosocial support for pediatrics and their families are part of the health responses to disaster and disaster recovery. Based on the bio-psycho-social model, some pediatrics may have catastrophic thoughts and are prone to experience despair, numbness, flashback and other serious emotional and behavioral reactions. In severe cases, there may be symptoms of psychosis or post-traumatic stress disorder. Timely and appropriate protections are needed to prevent the occurrence of psychological and behavioral problems. The emerging digital applications and health services such as telehealth, social media, mobile health and remote interactive online education are able to bridge the social distance and support mental and behavioral health for pediatric populations. Based on the psychological development characteristics of pediatrics, this study also illustrates interventions on the psychological impact from the COVID-19 pandemic. Even though the world has been struggling to curb the influences of the pandemic, the quarantine and social distancing policies will have long-term impacts on pediatrics. Innovative digital solutions and informatics tools are needed more than ever to mitigate the negative consequences on pediatrics. Healthcare delivery and services should envision and implement innovative paradigms to meet broad well-being needs and pediatric health as the quarantine and social distancing over a longer term become a new reality. Future research on pediatric mental and behavioral health should pay more attention to novel solutions that incorporate cutting edge interactive technologies and digital approaches, leveraging considerable advances in pervasive and ubiquitous computing, human-computer interaction, health informatics and among many others. Digital approaches, health technologies and informatics are supposed to be designed and implemented to support public health surveillance and critical responses to pediatrics' growth and development. For instance, human-computer interactions, augmented reality and virtual reality could be incorporated to remote psychological supporting service for pediatric health; mobile technologies could be used to monitor pediatrics' mental and behavioral health while protecting their individual privacy; big data and artificial intelligences could be utilized to support decision-making on whether pediatrics should go out for physical activities and whether schools should be reopened, etc. Implications to clinical practice, psychological therapeutic practices and future research directions to address current efforts gaps have been highlighted.", "qid": 45, "docid": "jrvurm62", "rank": 68, "score": 10.15429973602295}, {"content": "Title: Pediatric mental and behavioral health in the period of quarantine and social distancing (COVID-19). Content: UNSTRUCTURED The COVID-19 pandemic has spread rapidly throughout the world and has generated a long-term impact. The pandemic has caused great harm to society and also caused serious psychological trauma to many people. Pediatrics are a vulnerable group in this global public health emergency, as their nervous systems, endocrine systems and hypothalamic-pituitary-adrenal axes are not well developed. Psychological crises often cause pediatrics to produce feelings of abandonment, despair, incapacity and exhaustion, and even raising the risk of suicide. Children with mental illnesses are especially vulnerable during the quarantine and social distancing period. The inclusion of psychosocial support for pediatrics and their families are part of the health responses to disaster and disaster recovery. Based on the bio-psycho-social model, some pediatrics may have catastrophic thoughts and are prone to experience despair, numbness, flashback and other serious emotional and behavioral reactions. In severe cases, there may be symptoms of psychosis or post-traumatic stress disorder. Timely and appropriate protections are needed to prevent the occurrence of psychological and behavioral problems. The emerging digital applications and health services such as telehealth, social media, mobile health and remote interactive online education are able to bridge the social distance and support mental and behavioral health for pediatric populations. Based on the psychological development characteristics of pediatrics, this study also illustrates interventions on the psychological impact from the COVID-19 pandemic. Even though the world has been struggling to curb the influences of the pandemic, the quarantine and social distancing policies will have long-term impacts on pediatrics. Innovative digital solutions and informatics tools are needed more than ever to mitigate the negative consequences on pediatrics. Healthcare delivery and services should envision and implement innovative paradigms to meet broad well-being needs and pediatric health as the quarantine and social distancing over a longer term become a new reality. Future research on pediatric mental and behavioral health should pay more attention to novel solutions that incorporate cutting edge interactive technologies and digital approaches, leveraging considerable advances in pervasive and ubiquitous computing, human-computer interaction, health informatics and among many others. Digital approaches, health technologies and informatics are supposed to be designed and implemented to support public health surveillance and critical responses to pediatrics' growth and development. For instance, human-computer interactions, augmented reality and virtual reality could be incorporated to remote psychological supporting service for pediatric health; mobile technologies could be used to monitor pediatrics' mental and behavioral health while protecting their individual privacy; big data and artificial intelligences could be utilized to support decision-making on whether pediatrics should go out for physical activities and whether schools should be reopened, etc. Implications to clinical practice, psychological therapeutic practices and future research directions to address current efforts gaps have been highlighted.", "qid": 45, "docid": "leh2ny0e", "rank": 69, "score": 10.154298782348633}, {"content": "Title: How do Funeral Practices impact Bereaved Relatives' Mental Health, Grief and Bereavement? A Mixed Methods Review with Implications for COVID-19. Content: Those who are bereaved during the current COVID-19 pandemic are subject to restrictions on funeral sizes and practices. We conducted a rapid review synthesising the quantitative and qualitative evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes. Searches of MEDLINE, PsycINFO, KSR Evidence, and COVID-related resources were conducted. 805 records were screened; 17 studies of variable quality were included. Current evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes is inconclusive. Five observational studies found benefits from funeral participation while six did not. However, qualitative research provides additional insight: the benefit of after-death rituals including funerals depends on the ability of the bereaved to shape those rituals and say goodbye in a way which is meaningful for them. Findings highlight the important role of funeral officiants during the pandemic. Research is needed to better understand the experiences and sequalae of grief and bereavement during COVID-19.", "qid": 45, "docid": "arvxidyo", "rank": 70, "score": 10.127699851989746}, {"content": "Title: How do Funeral Practices impact Bereaved Relatives' Mental Health, Grief and Bereavement? A Mixed Methods Review with Implications for COVID-19 Content: Those who are bereaved during the current COVID-19 pandemic are subject to restrictions on funeral sizes and practices. We conducted a rapid review synthesising the quantitative and qualitative evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes. Searches of MEDLINE, PsycINFO, KSR Evidence, and COVID-related resources were conducted. 805 records were screened; 17 studies of variable quality were included. Current evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes is inconclusive. Five observational studies found benefits from funeral participation while six did not. However, qualitative research provides additional insight: the benefit of after-death rituals including funerals depends on the ability of the bereaved to shape those rituals and say goodbye in a way which is meaningful for them. Findings highlight the important role of funeral officiants during the pandemic. Research is needed to better understand the experiences and sequalae of grief and bereavement during COVID-19.", "qid": 45, "docid": "m4n87qz2", "rank": 71, "score": 10.12769889831543}, {"content": "Title: Mental health issues and psychological crisis interventions during the COVID-19 pandemic and earthquakes in Croatia/ Mentalno zdravlje i psiholo\u0161ke krizne intervencije tijekom COVID-19 pandemije i potresa u Hrvatskoj Content: The newly discovered coronavirus, now called SARS-CoV-2, was first detected in Wuhan, China as a cause of severe acute respiratory syndrome, disease called COVID-19. From the beginning of 2020 it rapidly spread, affecting the whole world, but with a major impact in Europe and North America. At the moment of writing, there are more than 2 million confirmed cases with more than 125.000 confirmed deaths related to COVID-19 globally. In Croatia, there are currently 1.741 confirmed cases with 34 deaths related to the virus. The COVID-19 rapid spread and magnitude of pandemic unleashed panic among people which warrants public health officials to also address the epidemic of fear. Research on the psychological reactions to previous epidemics and pandemics suggests that various psychological factors may play a role in coronaphobia. Nov-elty and uncertainty what the unknown brings is likely the cause of COVID-19 fear. With the sharp increase in number of affected persons by pandemic, both infected or suspected cases in isolation, fear and anxiety grew in general population, which warranted a significant increase in need for psychiatric support for both patients and medical staff. After initial stabilization of the situation and a prompt response to increased needs for mental support, during this time of pandemic, self-isolations and imposed social distancing, the strongest earthquake this city has experienced in the last 140 years hit Croatian capital Zagreb. During these trying times, maintaining good mental health of both medical personnel as well as the general population is crucial for both health and mental damage control. In Croatia, crisis interventions aimed for those most exposed to mental impact of pandemic and natural disasters is limited.", "qid": 45, "docid": "gokevnzw", "rank": 72, "score": 10.120599746704102}, {"content": "Title: Psychological Intervention and COVID-19: What We Know So Far and What We Can Do Content: The coronavirus COVID-19 and the global pandemic has already had a substantial disruptive impact on society, posing major challenges to the provision of mental health services in a time of crisis, and carrying the spectre of an increased burden to mental health, both in terms of existing psychiatric disorder, and emerging psychological distress from the pandemic. In this paper we provide a framework for understanding the key challenges for psychologically informed mental health care during and beyond the pandemic. We identify three groups that can benefit from psychological approaches to mental health, and/or interventions relating to COVID-19. These are (i) healthcare workers engaged in frontline response to the pandemic and their patients; (ii) individuals who will experience the emergence of new mental health distress as a function of being diagnosed with COVID-19, or losing family and loved ones to the illness, or the psychological effects of prolonged social distancing; and (iii) individuals with existing mental health conditions who are either diagnosed with COVID-19 or whose experience of social distancing exacerbates existing vulnerabilities. Drawing on existing literature and our own experience of adapting treatments to the crisis we suggest a number of salient points to consider in identifying risks and offering support to all three groups. We also offer a number of practical and technical considerations for working psychotherapeutically with existing patients where COVID-19 restrictions have forced a move to online or technologically mediated delivery of psychological interventions.", "qid": 45, "docid": "9qh7efs4", "rank": 73, "score": 10.105600357055664}, {"content": "Title: COVID-19 and telepsychiatry: Early outpatient experiences and implications for the future Content: The COVID-19 pandemic has dramatically transformed the U.S. healthcare landscape. Within psychiatry, a sudden relaxing of insurance and regulatory barriers during the month of March 2020 enabled clinicians practicing in a wide range of settings to quickly adopt virtual care in order to provide critical ongoing mental health supports to both existing and new patients struggling with the pandemic's impact. In this article, we briefly review the extensive literature supporting the effectiveness of telepsychiatry relative to in-person mental health care, and describe how payment and regulatory challenges were the primary barriers preventing more widespread adoption of this treatment modality prior to COVID-19. We then review key changes that were implemented at the federal, state, professional, and insurance levels over a one-month period that helped usher in an unprecedented transformation in psychiatric care delivery, from mostly in-person to mostly virtual. Early quality improvement data regarding virtual visit volumes and clinical insights from our outpatient psychiatry department located within a large, urban, tertiary care academic medical center reflect both the opportunities and challenges of virtual care for patients and providers. Finally, we provide clinical suggestions for optimizing telepsychiatry based on our experience, make a call for advocacy to continue the reduced insurance and regulatory restrictions affecting telepsychiatry even once this public health crisis has passed, and pose research questions that can help guide optimal utilization of telepsychiatry as mainstay or adjunct of outpatient psychiatric treatment now and in the future.", "qid": 45, "docid": "cwtdkylo", "rank": 74, "score": 10.091699600219727}, {"content": "Title: Psychosocial impact of COVID-19 Content: BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as \"coronaphobia\", has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- \"COVID-19\", \"SARS-CoV2\", \"Pandemic\", \"Psychology\", \"Psychosocial\", \"Psychitry\", \"marginalized\", \"telemedicine\", \"mental health\", \"quarantine\", \"infodemic\", \"social media\" and\" \"internet\". Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multiplied by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an \"infodemic\" spread via different platforms of social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.", "qid": 45, "docid": "5zg5g77w", "rank": 75, "score": 10.071599960327148}, {"content": "Title: Psychosocial impact of COVID-19 Content: BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as \u201ccoronaphobia\u201d, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- \u201cCOVID-19\u201d, \u201cSARS-CoV2\u201d, \u201cPandemic\u201d, \u201cPsychology\u201d, \u201cPsychosocial\u201d, \u201cPsychitry\u201d, \u201cmarginalized\u201d, \u201ctelemedicine\u201d, \u201cmental health\u201d, \u201cquarantine\u201d, \u201cinfodemic\u201d, \u201csocial media\u201d and\u201d \u201cinternet\u201d. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an \u201cinfodemic\u201d spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.", "qid": 45, "docid": "h0yzj1ro", "rank": 76, "score": 10.071599006652832}, {"content": "Title: Burnout and Posttraumatic Stress Disorder in the Coronavirus Disease 2019 (COVID-19) Pandemic: Intersection, Impact, and Interventions Content: The coronavirus disease 2019 (COVID 2019) pandemic has presented myriad challenges to an underprepared health care system. Health care providers are facing unprecedented acute workplace stress compounded by a high baseline rate of physician burnout. This article discusses the relationship between acute stress disorder, posttraumatic stress disorder, and burnout through a literature review focusing on the mental health impact on health care providers after prior epidemics and natural disasters. We offer both a framework for understanding the mental health impact of the COVID-19 epidemic on physicians while proposing a systems based model to respond to these challenges.", "qid": 45, "docid": "bmbdtxj0", "rank": 77, "score": 10.069000244140625}, {"content": "Title: Is the mental health of young students and their family members affected during the quarantine period? Evidence from the COVID-19 pandemic in Albania Content: INTRODUCTION: The use of quarantine method has a significant impact on mental health status. AIM: This study aimed to assess the levels of depression among bachelor and master university students (nurses/midwives) and their family members' during the quarantine period of COVID-19 pandemic. METHOD: A cross-sectional study was conducted in Vlora University, Albania. Patient Health Questionnaire (PHQ-9) was used. Institutional e-mails of all active students were used for their recruitment. RESULTS: In total, 863 students and 249 family members participated in the study. The mean PHQ-9 score was 6.220 (SD=5.803) and 6.280 (SD=5.857) for students and family members, respectively. Being unsatisfied with COVID-19 prevention measures, beliefs that COVID-19 infection and quarantine process can cause problems on their health status were the key factors for students to be screened positive for mental problems in multiple regression analysis. For parents, the last two factors were found to contribute significantly. DISCUSSION: Our findings indicate that quarantine measures have a significant impact on the levels of depression among both university students and their family members. Broader population studies are necessary to safeguard these results. IMPLICATIONS FOR PRACTICE: Provision of mental health services during the quarantine period is of paramount significance. Mental health first aid trainingand support could benefit both students and their parents significantly. Additionally, follow up services after the end of quarantine are recommended.", "qid": 45, "docid": "88gb52j8", "rank": 78, "score": 10.056599617004395}, {"content": "Title: Is the mental health of young students and their family members affected during the quarantine period? Evidence from the COVID-19 pandemic in Albania. Content: INTRODUCTION The use of quarantine method has a significant impact on mental health status. AIM This study aimed to assess the levels of depression among bachelor and master university students (nurses/midwives) and their family members' during the quarantine period of COVID-19 pandemic. METHOD A cross-sectional study was conducted in Vlora University, Albania. Patient Health Questionnaire (PHQ-9) was used. Institutional e-mails of all active students were used for their recruitment. RESULTS In total, 863 students and 249 family members participated in the study. The mean PHQ-9 score was 6.220 (SD=5.803) and 6.280 (SD=5.857) for students and family members, respectively. Being unsatisfied with COVID-19 prevention measures, beliefs that COVID-19 infection and quarantine process can cause problems on their health status were the key factors for students to be screened positive for mental problems in multiple regression analysis. For parents, the last two factors were found to contribute significantly. DISCUSSION Our findings indicate that quarantine measures have a significant impact on the levels of depression among both university students and their family members. Broader population studies are necessary to safeguard these results. IMPLICATIONS FOR PRACTICE Provision of mental health services during the quarantine period is of paramount significance. Mental health first aid trainingand support could benefit both students and their parents significantly. Additionally, follow up services after the end of quarantine are recommended.", "qid": 45, "docid": "a4ulg4ck", "rank": 79, "score": 10.056598663330078}, {"content": "Title: The coronavirus (COVID\u201019) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS\u2010CoV\u20102 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID\u201019 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID\u201019 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID\u201019 outbreak on the mental health of people.", "qid": 45, "docid": "0n5n7p4b", "rank": 80, "score": 10.055000305175781}, {"content": "Title: The coronavirus (COVID-19) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.", "qid": 45, "docid": "5cmcri6u", "rank": 81, "score": 10.054999351501465}, {"content": "Title: Impact of COVID-19 on the mental health of surgeons and coping strategies Content: Unprecedented times call for extraordinary measures. While surgeons across the globe try to comprehend the evolving facade of the COVID-19 pandemic and improvise surgical practice to the best of their ability, the psychological impact of the stress on their own mental health and well-being has been underestimated. This paper aims to review the indirect and overt factors that may affect the mental health of a surgeon in the present circumstances. Furthermore, it will aim to highlight key coping mechanisms at an individual and institutional level, so as to mitigate the negative psychological impact on surgeons.", "qid": 45, "docid": "w2lqk84x", "rank": 82, "score": 10.043999671936035}, {"content": "Title: Impact of COVID\u201019 on the mental health of surgeons and coping strategies Content: Unprecedented times call for extraordinary measures. While surgeons across the globe try to comprehend the evolving facade of the COVID\u201019 pandemic and improvise surgical practice to the best of their ability, the psychological impact of the stress on their own mental health and well\u2010being has been underestimated. This paper aims to review the indirect and overt factors that may affect the mental health of a surgeon in the present circumstances. Furthermore, it will aim to highlight key coping mechanisms at an individual and institutional level, so as to mitigate the negative psychological impact on surgeons.", "qid": 45, "docid": "y7yakmoc", "rank": 83, "score": 10.043998718261719}, {"content": "Title: Acute mental health responses during the COVID-19 pandemic in Australia Content: The acute and long-term mental health impacts of the COVID-19 pandemic are unknown. The current study examined the acute mental health responses to the COVID-19 pandemic in 5070 adult participants in Australia, using an online survey administered during the peak of the outbreak in Australia (27th March to 7th April 2020). Self-report questionnaires examined COVID-19 fears and behavioural responses to COVID-19, as well as the severity of psychological distress (depression, anxiety and stress), health anxiety, contamination fears, alcohol use, and physical activity. 78% of respondents reported that their mental health had worsened since the outbreak, one quarter (25.9%) were very or extremely worried about contracting COVID-19, and half (52.7%) were worried about family and friends contracting COVID-19. Uncertainty, loneliness and financial worries (50%) were common. Rates of elevated psychological distress were higher than expected, with 62%, 50%, and 64% of respondents reporting elevated depression, anxiety and stress levels respectively, and one in four reporting elevated health anxiety in the past week. Participants with self-reported history of a mental health diagnosis had significantly higher distress, health anxiety, and COVID-19 fears than those without a prior mental health diagnosis. Demographic (e.g., non-binary or different gender identity; Aboriginal and Torres Strait Islander status), occupational (e.g., being a carer or stay at home parent), and psychological (e.g., perceived risk of contracting COVID-19) factors were associated with distress. Results revealed that precautionary behaviours (e.g., washing hands, using hand sanitiser, avoiding social events) were common, although in contrast to previous research, higher engagement in hygiene behaviours was associated with higher stress and anxiety levels. These results highlight the serious acute impact of COVID-19 on the mental health of respondents, and the need for proactive, accessible digital mental health services to address these mental health needs, particularly for those most vulnerable, including people with prior history of mental health problems. Longitudinal research is needed to explore long-term predictors of poor mental health from the COVID-19 pandemic.", "qid": 45, "docid": "fzusgbww", "rank": 84, "score": 10.043100357055664}, {"content": "Title: Decreased utilization of mental health emergency service during the COVID-19 pandemic Content: During the rapid rise of the COVID-19 pandemic, a reduction of the numbers of patients presenting to emergency departments has been observed. We present an early study from a German psychiatric hospital to assess the dynamics of mental health emergency service utilization rates during the COVID-19 pandemic. Our results show that the numbers of emergency presentations decreased, and a positive correlation between these numbers and mobility of the general public suggests an impact of extended measures of social distancing. This finding underscores the necessity of raising and sustaining awareness regarding the threat to mental health in the context of the pandemic.", "qid": 45, "docid": "unhdfzpc", "rank": 85, "score": 10.032899856567383}, {"content": "Title: Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry Content: Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.", "qid": 45, "docid": "2wam1qls", "rank": 86, "score": 10.02079963684082}, {"content": "Title: Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry. Content: Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.", "qid": 45, "docid": "qkjyv0d2", "rank": 87, "score": 10.020798683166504}, {"content": "Title: Coping with COVID-19: Exposure to COVID-19 and Negative Impact on Livelihood Predict Elevated Mental Health Problems in Chinese Adults Content: The COVID-19 pandemic might lead to more mental health problems. However, few studies have examined sleep problems, depression, and posttraumatic symptoms among the general adult population during the COVID-19 outbreak, and little is known about coping behaviors. This survey was conducted online in China from February 1st to February 10th, 2020. Quota sampling was used to recruit 2993 Chinese citizens aged \u226518 years old. Mental health problems were assessed with the Post-Traumatic Stress Disorders (PTSD) Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Center for Epidemiological Studies Depression inventory, and the Pittsburgh Sleep Quality Index. Exposure to COVID-19 was measured with questions about residence at outbreak, personal exposure, media exposure, and impact on livelihood. General coping style was measured by the brief Coping Style Questionnaire (SCSQ). Respondents were also asked 12 additional questions about COVID-19 specific coping behaviors. Direct exposure to COVID-19 instead of the specific location of (temporary) residence within or outside the epicenter (Wuhan) of the pandemic seems important (standardized beta: 0.05, 95% confidence interval (CI): 0.02\u20130.09). Less mental health problems were also associated with less intense exposure through the media (standardized beta: \u22120.07, 95% CI: \u22120.10\u2013\u22120.03). Perceived negative impact of the pandemic on livelihood showed a large effect size in predicting mental health problems (standardized beta: 0.15, 95% CI: 0.10\u20130.19). More use of cognitive and prosocial coping behaviors were associated with less mental health problems (standardized beta: \u22120.30, 95% CI: \u22120.34\u2013\u22120.27). Our study suggests that the mental health consequences of the lockdown impact on livelihood should not be underestimated. Building on cognitive coping behaviors reappraisal or cognitive behavioral treatments may be most promising.", "qid": 45, "docid": "1kpw4ru0", "rank": 88, "score": 10.007100105285645}, {"content": "Title: Coping with COVID-19: Exposure to COVID-19 and Negative Impact on Livelihood Predict Elevated Mental Health Problems in Chinese Adults Content: The COVID-19 pandemic might lead to more mental health problems. However, few studies have examined sleep problems, depression, and posttraumatic symptoms among the general adult population during the COVID-19 outbreak, and little is known about coping behaviors. This survey was conducted online in China from February 1st to February 10th, 2020. Quota sampling was used to recruit 2993 Chinese citizens aged &#8805;18 years old. Mental health problems were assessed with the Post-Traumatic Stress Disorders (PTSD) Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Center for Epidemiological Studies Depression inventory, and the Pittsburgh Sleep Quality Index. Exposure to COVID-19 was measured with questions about residence at outbreak, personal exposure, media exposure, and impact on livelihood. General coping style was measured by the brief Coping Style Questionnaire (SCSQ). Respondents were also asked 12 additional questions about COVID-19 specific coping behaviors. Direct exposure to COVID-19 instead of the specific location of (temporary) residence within or outside the epicenter (Wuhan) of the pandemic seems important (standardized beta: 0.05, 95% confidence interval (CI): 0.02-0.09). Less mental health problems were also associated with less intense exposure through the media (standardized beta: -0.07, 95% CI: -0.10--0.03). Perceived negative impact of the pandemic on livelihood showed a large effect size in predicting mental health problems (standardized beta: 0.15, 95% CI: 0.10-0.19). More use of cognitive and prosocial coping behaviors were associated with less mental health problems (standardized beta: -0.30, 95% CI: -0.34--0.27). Our study suggests that the mental health consequences of the lockdown impact on livelihood should not be underestimated. Building on cognitive coping behaviors reappraisal or cognitive behavioral treatments may be most promising.", "qid": 45, "docid": "pavnpgu8", "rank": 89, "score": 10.007099151611328}, {"content": "Title: Psychological health during the coronavirus disease 2019 pandemic outbreak. Content: BACKGROUND The current ongoing pandemic outbreak of COVID-19 (Coronavirus Disease 2019) has globally affected 213 countries and territories with more than 2.5 million confirmed cases and thousands of casualties. The unpredictable and uncertain COVID-19 outbreak has the potential of adversely affecting the psychological health on individual and community level. Currently all efforts are focused on the understanding of epidemiology, clinical features, mode of transmission, counteract the spread of the virus, and challenges of global health, while crucially significant mental health has been overlooked in this endeavor. METHOD This review is to evaluate past outbreaks to understand the extent of adverse effects on psychological health, psychological crisis intervention, and mental health management plans. Published previous and current articles on PubMed, EMBASE, Google Scholar, and Elsevier about psychological impact of infectious diseases outbreaks and COVID-19 has been considered and reviewed. COMMENTS COVID-19 is leading to intense psychosocial issues and comprising mental health marking a secondary health concern all around the world. Globally implementing preventive and controlling measures, and cultivating coping and resilience are challenging factors; modified lifestyle (lockdown curfew, self-isolation, social distancing and quarantine); conspiracy theories, misinformation and disinformation about the origin, scale, signs, symptoms, transmission, prevention and treatment; global socioeconomic crisis; travel restrictions; workplace hazard control; postponement and cancellation of religious, sports, cultural and entertainment events; panic buying and hoarding; incidents of racism, xenophobia, discrimination, stigma, psychological pressure of productivity, marginalization and violence; overwhelmed medical centers and health organizations, and general impact on education, politics, socioeconomic, culture, environment and climate - are some of the risk factors to aggravate further problems.", "qid": 45, "docid": "ka7nvqcc", "rank": 90, "score": 9.987600326538086}, {"content": "Title: Psychological health during the coronavirus disease 2019 pandemic outbreak Content: BACKGROUND: The current ongoing pandemic outbreak of COVID-19 (Coronavirus Disease 2019) has globally affected 213 countries and territories with more than 2.5 million confirmed cases and thousands of casualties. The unpredictable and uncertain COVID-19 outbreak has the potential of adversely affecting the psychological health on individual and community level. Currently all efforts are focused on the understanding of epidemiology, clinical features, mode of transmission, counteract the spread of the virus, and challenges of global health, while crucially significant mental health has been overlooked in this endeavor. METHOD: This review is to evaluate past outbreaks to understand the extent of adverse effects on psychological health, psychological crisis intervention, and mental health management plans. Published previous and current articles on PubMed, EMBASE, Google Scholar, and Elsevier about psychological impact of infectious diseases outbreaks and COVID-19 has been considered and reviewed. COMMENTS: COVID-19 is leading to intense psychosocial issues and comprising mental health marking a secondary health concern all around the world. Globally implementing preventive and controlling measures, and cultivating coping and resilience are challenging factors; modified lifestyle (lockdown curfew, self-isolation, social distancing and quarantine); conspiracy theories, misinformation and disinformation about the origin, scale, signs, symptoms, transmission, prevention and treatment; global socioeconomic crisis; travel restrictions; workplace hazard control; postponement and cancellation of religious, sports, cultural and entertainment events; panic buying and hoarding; incidents of racism, xenophobia, discrimination, stigma, psychological pressure of productivity, marginalization and violence; overwhelmed medical centers and health organizations, and general impact on education, politics, socioeconomic, culture, environment and climate - are some of the risk factors to aggravate further problems.", "qid": 45, "docid": "zgzjl8uy", "rank": 91, "score": 9.98759937286377}, {"content": "Title: The Mental Health Consequences of Coronavirus Disease 2019 Pandemic in Dentistry Content: With the spread of coronavirus disease 2019 (COVID-19), strict isolation strategies to limit virus transmission have been applied worldwide. The lockdown has affected and challenged different medical areas. Doctors, nurses, dentists, and other health care workers are concerned about contagion, not only for themselves, but also for their families and colleagues. Furthermore, the oral mucosa has been accepted as a high-risk route of transmission for COVID-19. In many countries, dentists have been forced to stop working during quarantine until further notification. Isolation and its financial impact have produced physical and psychological pressure, depression, social anxiety, and other mental health concerns. This article aims to provide a comprehensive review of the consequences of past epidemics on mental health and to assess possible aspects that might be associated with mental implications in dentists during the COVID-19 pandemic. Finally, some concrete actions to avoid subsequent potential consequences are recommended.", "qid": 45, "docid": "mitvv9rp", "rank": 92, "score": 9.976300239562988}, {"content": "Title: COVID-19 pandemic: challenges and opportunities for the Greek health care system Content: After coming out of the state debt crisis, Greece is facing yet another crisis - that of the COVID-19 pandemic. The key challenges facing the organizational structure and function of the Greek public health system in order to meet the populations' health needs are discussed. Social distancing, through imposed national lockdown very early in the pandemic, has been a key emergency public health measure that has saved lives. However, the system needs to enhance its capacity, through strengthening primary health and social support care, to be able to meet existing unmet health needs, the impact of the pandemic on mental health, as well as to tackle future new waves of outbreak. The related changes in health service provisions in response to the COVID-19 pandemic call for developing new models and novel approaches for delivering effective mental health services.", "qid": 45, "docid": "o39l38jk", "rank": 93, "score": 9.970999717712402}, {"content": "Title: COVID-19 pandemic: challenges and opportunities for the Greek health care system Content: After coming out of the state debt crisis, Greece is facing yet another crisis \u2013 that of the COVID-19 pandemic. The key challenges facing the organizational structure and function of the Greek public health system in order to meet the populations\u2019 health needs are discussed. Social distancing, through imposed national lockdown very early in the pandemic, has been a key emergency public health measure that has saved lives. However, the system needs to enhance its capacity, through strengthening primary health and social support care, to be able to meet existing unmet health needs, the impact of the pandemic on mental health, as well as to tackle future new waves of outbreak. The related changes in health service provisions in response to the COVID-19 pandemic call for developing new models and novel approaches for delivering effective mental health services.", "qid": 45, "docid": "zmhuoqhg", "rank": 94, "score": 9.970998764038086}, {"content": "Title: Attending to the Emotional Well-Being of the Health Care Workforce in a New York City Health System During the COVID-19 Pandemic Content: The COVID-19 pandemic has placed an enormous strain on health care workers, and its potential impact has implications for the physical and emotional well-being of the work force. As hospital systems run far over capacity, facing possible shortages of critical care medical resources and personal protective equipment as well as clinician deaths, the psychological stressors necessitate a strong well-being support model for staff. At the Mount Sinai Health System (MSHS) in New York City, health care workers have been heroically providing frontline care to COVID-19 patients while facing their own appropriate fears for their personal safety in the setting of contagion. This moral obligation cannot be burdened by unacceptable risks; the health system\u2019s full support is required to address the needs of its workforce. In this Invited Commentary, the authors describe how an MSHS Employee, Faculty, and Trainee Crisis Support Task Force\u2014created in early March 2020 and composed of behavioral health, human resources, and well-being leaders from across the health system\u2014used a rapid needs assessment model to capture the concerns of the workforce related to the COVID-19 pandemic. The task force identified 3 priority areas central to promoting and maintaining the well-being of the entire MSHS workforce during the pandemic: meeting basic daily needs; enhancing communications for delivery of current, reliable, and reassuring messages; and developing robust psychosocial and mental health support options. Using a work group strategy, the task force operationalized the rollout of support initiatives for each priority area. Attending to the emotional well-being of health care workers has emerged as a central element in the MSHS COVID-19 response, which continues to be committed to the physical and emotional needs of a workforce that courageously faces this crisis.", "qid": 45, "docid": "f634kpug", "rank": 95, "score": 9.966099739074707}, {"content": "Title: Attending to the Emotional Well-Being of the Health Care Workforce in a New York City Health System During the COVID-19 Pandemic Content: The COVID-19 pandemic has placed an enormous strain on health care workers, and its potential impact has implications for the physical and emotional well-being of the work force. As hospital systems run far over capacity, facing possible shortages of critical care medical resources and personal protective equipment as well as clinician deaths, the psychological stressors necessitate a strong well-being support model for staff. At the Mount Sinai Health System (MSHS) in New York City, health care workers have been heroically providing front-line care to COVID-19 patients while facing their own appropriate fears for their personal safety in the setting of contagion. This moral obligation cannot be burdened by unacceptable risks; the health system's full support is required to address the needs of its workforce.In this Invited Commentary, the authors describe how an MSHS Employee, Faculty, and Trainee Crisis Support Task Force-created in early March 2020 and composed of behavioral health, human resources, and well-being leaders from across the health system-used a rapid needs assessment model to capture the concerns of the workforce related to the COVID-19 pandemic. The task force identified 3 priority areas central to promoting and maintaining the well-being of the entire MSHS workforce during the pandemic: meeting basic daily needs; enhancing communications for delivery of current, reliable, and reassuring messages; and developing robust psychosocial and mental health support options. Using a work group strategy, the task force operationalized the roll-out of support initiatives for each priority area. Attending to the emotional well-being of health care workers has emerged as a central element in the MSHS COVID-19 response, which continues to be committed to the physical and emotional needs of a workforce that courageously faces this crisis.", "qid": 45, "docid": "x1km7nfn", "rank": 96, "score": 9.96609878540039}, {"content": "Title: Impact of the COVID-19 Pandemic on Mental Health and Quality of Life among Local Residents in Liaoning Province, China: A Cross-Sectional Study Content: Our study aimed to investigate the immediate impact of the COVID-19 pandemic on mental health and quality of life among local Chinese residents aged &#8805;18 years in Liaoning Province, mainland China. An online survey was distributed through a social media platform between January and February 2020. Participants completed a modified validated questionnaire that assessed the Impact of Event Scale (IES), indicators of negative mental health impacts, social and family support, and mental health-related lifestyle changes. A total of 263 participants (106 males and 157 females) completed the study. The mean age of the participants was 37.7 \u00b1 14.0 years, and 74.9% had a high level of education. The mean IES score in the participants was 13.6 \u00b1 7.7, reflecting a mild stressful impact. Only 7.6% of participants had an IES score &#8805;26. The majority of participants (53.3%) did not feel helpless due to the pandemic. On the other hand, 52.1% of participants felt horrified and apprehensive due to the pandemic. Additionally, the majority of participants (57.8-77.9%) received increased support from friends and family members, increased shared feeling and caring with family members and others. In conclusion, the COVID-19 pandemic was associated with mild stressful impact in our sample, even though the COVID-19 pandemic is still ongoing. These findings would need to be verified in larger population studies.", "qid": 45, "docid": "skwlq014", "rank": 97, "score": 9.955699920654297}, {"content": "Title: Impact of the COVID-19 Pandemic on Mental Health and Quality of Life among Local Residents in Liaoning Province, China: A Cross-Sectional Study Content: Our study aimed to investigate the immediate impact of the COVID-19 pandemic on mental health and quality of life among local Chinese residents aged \u226518 years in Liaoning Province, mainland China. An online survey was distributed through a social media platform between January and February 2020. Participants completed a modified validated questionnaire that assessed the Impact of Event Scale (IES), indicators of negative mental health impacts, social and family support, and mental health-related lifestyle changes. A total of 263 participants (106 males and 157 females) completed the study. The mean age of the participants was 37.7 \u00b1 14.0 years, and 74.9% had a high level of education. The mean IES score in the participants was 13.6 \u00b1 7.7, reflecting a mild stressful impact. Only 7.6% of participants had an IES score \u226526. The majority of participants (53.3%) did not feel helpless due to the pandemic. On the other hand, 52.1% of participants felt horrified and apprehensive due to the pandemic. Additionally, the majority of participants (57.8\u201377.9%) received increased support from friends and family members, increased shared feeling and caring with family members and others. In conclusion, the COVID-19 pandemic was associated with mild stressful impact in our sample, even though the COVID-19 pandemic is still ongoing. These findings would need to be verified in larger population studies.", "qid": 45, "docid": "wgim93nm", "rank": 98, "score": 9.95569896697998}, {"content": "Title: JAACAP's Role in Advancing the Science of Pediatric Mental Health and Promoting the Care of Youth and Families During the COVID-19 Pandemic Content: As we pen these words, the COVID-19 pandemic is having profound impacts on human society. Based on decades of research, we know that the accompanying illness,1 death,2 social isolation,3,4 and malnutrition5 will have deep and lasting impacts on our children and adolescents, their families, and the communities in which they develop. The pandemic is exposing, with terrible clarity, the disparities in human society-racism,6 poverty,7,8 domestic violence,9,10 and child maltreatment and neglect11-and tragically will likely amplify the negative impacts that each has on child development and mental health.", "qid": 45, "docid": "77dtxxd4", "rank": 99, "score": 9.940299987792969}, {"content": "Title: The COVID-19 Global Pandemic: Implications for People With Schizophrenia and Related Disorders Content: The coronavirus disease-19 (COVID-19) global pandemic has already had an unprecedented impact on populations around the world, and is anticipated to have a disproportionate burden on people with schizophrenia and related disorders. We discuss the implications of the COVID-19 global pandemic with respect to: (1) increased risk of infection and poor outcomes among people with schizophrenia, (2) anticipated adverse mental health consequences for people with schizophrenia, (3) considerations for mental health service delivery in inpatient and outpatient settings, and (4) potential impact on clinical research in schizophrenia. Recommendations emphasize rapid implementation of measures to both decrease the risk of COVID-19 transmission and maintain continuity of clinical care and research to preserve safety of both people with schizophrenia and the public.", "qid": 45, "docid": "q1sybzej", "rank": 100, "score": 9.917400360107422}]}
{"query": "what evidence is there for dexamethasone as a treatment for COVID-19?", "hits": [{"content": "Title: Multiple Myeloma in the Time of COVID-19 Content: We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10-12 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.", "qid": 46, "docid": "0eyi1gql", "rank": 1, "score": 8.891300201416016}, {"content": "Title: Multiple Myeloma in the Time of COVID-19 Content: We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10\u201312 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.", "qid": 46, "docid": "omen8vvq", "rank": 2, "score": 8.8912992477417}, {"content": "Title: COVID-19-associated ARDS treated with DEXamethasone (CoDEX): Study design and rationale for a randomized trial. Content: OBJECTIVES: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV2 infection (Coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop Acute Respiratory Distress Syndrome (ARDS). Several clinical trials evaluated the role of corticosteroids in non-COVID-19 ARDS with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe ARDS due to confirmed or probable COVID-19. METHODS: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48h before randomization) moderate or severe ARDS, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (intervention group) or standard treatment without dexamethasone (control group). Patients in the intervention group will receive dexamethasone 20mg IV once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until Intensive Care Unit (ICU) discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment (SOFA) Score evaluation at 48h, 72h and 7 days and ICU-free days within 28. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa - CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete.", "qid": 46, "docid": "dgy7qbl5", "rank": 3, "score": 8.45740032196045}, {"content": "Title: Systematic and Statistical Review of Coronavirus Disease 19 Treatment Trials Content: The following systematic review and meta-analysis compile the current data regarding human controlled COVID-19 treatment trials. An electronic search of the literature compiled studies pertaining to human controlled treatment trials with COVID-19. Medications assessed included lopinavir/ritonavir, arbidol, hydroxychloroquine, tocilizumab, favipiravir, heparin, and dexamethasone. Statistical analyses were performed for common viral clearance endpoints whenever possible. Lopinavir/ritonavir showed no significant effect on viral clearance for COVID-19 cases (OR 0.95 [95% CI 0.50\u20131.83]). Hydroxychloroquine also showed no significant effect on COVID-19 viral clearance rates (OR 2.16 [95% CI 0.80\u20135.84]). Arbidol showed no 7-day (OR 1.63 [95% CI 0.76\u20133.50]) or 14-day viral (OR 5.37 [95% CI 0.35\u201383.30]) clearance difference compared to lopinavir/ritonavir. Review of literature showed no significant clinical improvement with lopinavir/ritonavir, arbidol, hydroxychloroquine, or remdesivir. Tocilizumab showed mixed results regarding survival. Favipiravir showed quicker symptom improvement compared to lopinavir/ritonavir and arbidol. Heparin and dexamethasone showed improvement with severe COVID-19 cases requiring supplemental oxygenation. Current medications do not show significant effect on COVID-19 viral clearance rates. Tocilizumab showed mixed results regarding survival. Favipiravir shows favorable results compared to other tested medications. Heparin and dexamethasone show benefit especially for severe COVID-19 cases.", "qid": 46, "docid": "07tdrd4w", "rank": 4, "score": 8.381799697875977}, {"content": "Title: Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report Content: Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.", "qid": 46, "docid": "ocguwlam", "rank": 5, "score": 8.338199615478516}, {"content": "Title: Short-Term Dexamethasone in Sars-CoV-2 Patients Content: BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2 To date, there has been no definite therapy for COVID-19 We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone METHODS: We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies RESULTS: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129 52 to 40 73 mg/L at time of discharge 71% percent of the patients were discharged home with a mean length of stay of 7 8 days None of the patients had escalation of care, leading to mechanical ventilation Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care CONCLUSIONS: A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19 However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs", "qid": 46, "docid": "fqh77aaa", "rank": 6, "score": 8.214900016784668}, {"content": "Title: Short-Term Dexamethasone in Sars-CoV-2 Patients. Content: BACKGROUND Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. METHODS We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. RESULTS CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. CONCLUSIONS A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "qid": 46, "docid": "ztd7awzv", "rank": 7, "score": 8.214899063110352}, {"content": "Title: Cardiovascular Complications of COVID-19: Pharmacotherapy Perspective Content: Coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly the world over. The disease was declared \u201cpandemic\u201d by the World Health Organization. An approved therapy for patients with COVID-19 has yet to emerge; however, there are some medications used in the treatment of SARS-CoV-2 infection globally including hydroxychloroquine, remdesivir, dexamethasone, protease inhibitors, and anti-inflammatory agents. Patients with underlying cardiovascular disease are at increased risk of mortality and morbidity from COVID-19. Moreover, patients with chronic stable states and even otherwise healthy individuals might sustain acute cardiovascular problems due to COVID-19 infection. This article seeks to review the latest evidence with a view to explaining possible pharmacotherapies for the cardiovascular complications of COVID-19 including acute coronary syndrome, heart failure, myocarditis, arrhythmias, and venous thromboembolism, as well as possible interactions between these medications and those currently administered (or under evaluation) in the treatment of COVID-19.", "qid": 46, "docid": "qvsoinfy", "rank": 8, "score": 8.115400314331055}, {"content": "Title: CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial Content: BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It is the leading cause of death in HIV patients in Asia and Africa. No major advance has been made in the treatment of CM since the 1970s. The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest. Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM. Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested. The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality? Dexamethasone is a cheap, readily available, and practicable intervention. METHOD: A double-blind placebo-controlled trial with parallel arms in which patients are randomised to receive either dexamethasone or placebo, in addition to local standard of care. The study recruits patients in both Asia and Africa to ensure the relevance of its results to the populations in which the disease burden is highest. The 10-week mortality risk in the control group is expected to be between 30% and 50%, depending on location, and the target hazard ratio of 0.7 corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50% to 38%. Assuming an overall 10-week mortality of at least 30% in our study population, recruitment of 824 patients will be sufficient to observe the expected number of deaths. Allowing for some loss to follow-up, the total sample size for this study is 880 patients. To generate robust evidence across both continents, we aim to recruit roughly similar numbers of patients from each continent. The primary end point is 10-week mortality. Ethical approval has been obtained from Oxford University\u2019s Tropical Research Ethics Committee (OxTREC), and as locally mandated at each site. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN59144167 26-July-2012", "qid": 46, "docid": "eq8yjxy3", "rank": 9, "score": 7.991099834442139}, {"content": "Title: Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "qid": 46, "docid": "mapu4r1z", "rank": 10, "score": 7.987800121307373}, {"content": "Title: Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO(2)) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. Exclusion criteria: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours\u2019 time of admission. The intervention begins with the administration of dexamethasone based on the SpO(2) levels. If the level of SpO(2) does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours\u2019 time of admission and will be continued for 48-72 hours and then the SpO(2) level will be checked. Then, if the level of SpO(2) has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO(2) level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO(2) level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug\u2019s bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "qid": 46, "docid": "t9c26eld", "rank": 11, "score": 7.987799167633057}, {"content": "Title: Short-Term Corticosteroids in SARS-CoV2 Patients: Hospitalists' Perspective Content: Background: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. Methods: We describe a series of 21 patients who tested positive for SARS-CoV2 and were admitted to The Miriam Hospital in Providence and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. Results: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. Conclusions: A short course of systemic corticosteroids among inpatients with SARS-CoV2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "qid": 46, "docid": "oqgw6ao6", "rank": 12, "score": 7.973499774932861}, {"content": "Title: A critical evaluation of glucocorticoids in the treatment of severe COVID-19 Content: The viral infection by SARS-CoV-2, has revolutionized the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective, with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20% of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids\u2019 role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "qid": 46, "docid": "m2b836k8", "rank": 13, "score": 7.960299968719482}, {"content": "Title: Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada Content: PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT3 antagonists are recommended over dexamethasone.", "qid": 46, "docid": "b8p4l0yp", "rank": 14, "score": 7.92549991607666}, {"content": "Title: Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada Content: PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT(3) antagonists are recommended over dexamethasone.", "qid": 46, "docid": "gd6dd4qm", "rank": 15, "score": 7.925498962402344}, {"content": "Title: Dexamethasone for COVID-19? Not so fast Content: Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "qid": 46, "docid": "6q0y3ewu", "rank": 16, "score": 7.613100051879883}, {"content": "Title: Dexamethasone for COVID-19? Not so fast. Content: Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "qid": 46, "docid": "br3ahtf7", "rank": 17, "score": 7.613099098205566}, {"content": "Title: A critical evaluation of glucocorticoids in the management of severe COVID-19 Content: The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "qid": 46, "docid": "bhkmax7s", "rank": 18, "score": 7.567800045013428}, {"content": "Title: The effect of dexamethasone-induced immunosuppression on the development of faecal antibody and recovery from and resistance to rotavirus infection Content: Rotavirus-naive and rotavirus-immune gnotobiotic calves were treated with high doses of dexamethasone (DX) to suppress the immune system. Calves were then infected with a virulent rotavirus inoculum, J-160, to investigate the role of immune responses both in recovery from primary rotavirus infection and in resistance to secondary rotavirus infection. Treatment of calves with DX markedly suppressed in vitro responsiveness of peripheral blood lymphocytes to mitogens within 48 h of the start of DX treatment. Suppression was similar in rotavirus-naive and rotavirus-immune calves. In contrast, the effect of DX treatment on specific antibody responses differed depending on when DX treatment started in relation to rotavirus infection. When DX treatment commenced prior to primary rotavirus infection both systemic and local specific antibody responses were inhibited. These calves, in which mitogen and antibody responses were suppressed, exhibited greater clinical signs than did control calves after infection with virulent rotavirus, but virus excretion was affected in only one of the two calves. When DX treatment was started after primary rotavirus infection but before secondary infection, systemic and local antibody responses to the primary infection and to the challenge infection were not affected. These calves resisted challenge with virulent virus as did DX-untreated rotavirus-immune calves, even though mitogen responses were suppressed. We conclude that in a primary rotavirus infection, virus excretion ceased when both antibody and mitogen responses were suppressed. Resistance to secondary rotavirus infection occurred when mitogen responsiveness was suppressed, but when antibody levels were normal. Thus, no evidence was obtained that fully functional cell-mediated immune mechanisms are essential for resistance to rotavirus infection. Evidence was provided for the ability of parenteral treatment with DX to suppress mucosal as well as systemic antibody responses.", "qid": 46, "docid": "btnwopac", "rank": 19, "score": 7.485899925231934}, {"content": "Title: Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin for COVID-19: what is the evidence and what are the risks? Content: The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.", "qid": 46, "docid": "wnb4cltt", "rank": 20, "score": 7.414000034332275}, {"content": "Title: Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial Content: BACKGROUND: There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS: We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0\u00b75 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS: Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4\u00b78 days [95% CI 2\u00b757 to 7\u00b703]; p<0\u00b70001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15\u00b73% [-25\u00b79 to -4\u00b79]; p=0\u00b70047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION: Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING: Fundaci\u00f3n Mutua Madrile\u00f1a, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociaci\u00f3n Cient\u00edfica Pulm\u00f3n y Ventilaci\u00f3n Mec\u00e1nica.", "qid": 46, "docid": "3vvsa2wi", "rank": 21, "score": 7.238399982452393}, {"content": "Title: Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Content: BACKGROUND There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0\u00b75 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4\u00b78 days [95% CI 2\u00b757 to 7\u00b703]; p<0\u00b70001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15\u00b73% [-25\u00b79 to -4\u00b79]; p=0\u00b70047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING Fundaci\u00f3n Mutua Madrile\u00f1a, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociaci\u00f3n Cient\u00edfica Pulm\u00f3n y Ventilaci\u00f3n Mec\u00e1nica.", "qid": 46, "docid": "buz3o8x9", "rank": 22, "score": 7.238399028778076}, {"content": "Title: Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization. Content: OBJECTIVE Restenosis following endovascular treatment of the femoropopliteal segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. Although local drug delivery to the superficial femoral and popliteal arteries promises improved patency, data are currently limited. We hypothesized that improved percutaneous delivery of an anti-inflammatory compound into the adventitia of the femoropopliteal at the time of endovascular treatment would be safe, feasible, and decrease the inflammatory response. METHODS This was a prospective, investigator-initiated, phase I, first-in-man study testing the safety and feasibility of percutaneous adventitial delivery of dexamethasone. Following successful intervention, an adventitial microinfusion catheter was advanced over a 0.014-inch wire to the treated segment. Its microneedle (0.9 mm long \u00d7 140-\u03bcm diameter) was deployed into the adventitia to deliver dexamethasone (4 mg/mL) mixed with contrast agent (80:20 ratio), providing fluoroscopic visualization. The primary safety outcome measure was freedom from vessel dissection, thrombosis, or extravasation while the primary efficacy outcome was duplex-determined binary restenosis defined as a peak systolic velocity ratio >2.5. RESULTS Twenty patients with Rutherford clinical category 2-5 enrolled in this study. The mean age was 66, and 55% had diabetes mellitus. Treated lesion length was 8.9 \u00b1 5.3 cm, and 50% were chronic total occlusions. Eighty percent of treated lesions were in the distal superficial femoral or popliteal arteries. All lesions were treated by balloon angioplasty with provisional stenting (n = 6) for suboptimal result. Three patients were treated with atherectomy as well. A mean of 1.6 \u00b1 1.1 mg (0.5 \u00b1 0.3 mL) of dexamethasone sodium phosphate was injected per centimeter of lesion length. In total, a mean of 12.1 \u00b1 6.1 mg of dexamethasone was injected per patient. The mean number of injections required per lesion was 3.0 \u00b1 1.3 cm, minimum one and maximum six injections. There was 100% technical success of drug delivery and no procedural or drug-related adverse events. The mean Rutherford score decreased from 3.1 \u00b1 .7 (median, 3.0) preoperatively to .5 \u00b1 .7 at 6 months (median, 0.0; P < .00001). Over this same time interval, the index leg ankle-brachial index increased from .68 \u00b1 .15 to .89 \u00b1 .19 (P = .0003). The preoperative C-reactive protein in this study was 6.9 \u00b1 8.5 indicating severe baseline inflammation, which increased to 14.0 \u00b1 23.1 mg/L (103% increase) at 24 hours following the procedure. However, this increase did not reach statistical significance of P = .14. Two patients met the primary efficacy end point of loss of primary patency by reoccluding their treated segment of the index lesion during the follow-up period. CONCLUSIONS Adventitial drug delivery via a microinfusion catheter is a safe and feasible alternative to intimal-based methods for adjunctive treatment in the femoropopliteal segment. The 6-month preliminary results suggest perivascular dexamethasone treatment may improve outcomes following angioplasty to the femoral and popliteal arteries, and support further clinical investigation of this approach.", "qid": 46, "docid": "4e05h96h", "rank": 23, "score": 7.227200031280518}, {"content": "Title: Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective Content: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "qid": 46, "docid": "hswuwtod", "rank": 24, "score": 7.218699932098389}, {"content": "Title: Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician\u2019s perspective Content: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "qid": 46, "docid": "zi86r481", "rank": 25, "score": 7.218698978424072}, {"content": "Title: Hydroxychloroquine as prophylaxis or treatment for COVID-19: What does the evidence say? Content: Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.", "qid": 46, "docid": "9eo0leey", "rank": 26, "score": 7.200799942016602}, {"content": "Title: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.", "qid": 46, "docid": "safr9z37", "rank": 27, "score": 7.165500164031982}, {"content": "Title: Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider? Content: The ongoing pandemic caused by severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. Patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. Numerous reports have shown that infection with SARS-CoV-2 causes depletion of B- and T-lymphocytes, including CD4 and CD8 T-cells, and is associated with severe illness and death and that patients with higher lymphocyte levels may have better outcomes. Dexamethasone, a widely prescribed antiemetic for acute and delayed nausea and vomiting from a variety of cancer drugs, causes B and T cell depletion, which may augment immunosuppression. Since it seems that lymphocytes are vital in the immune response to novel coronavirus, oncologists should reconsider the routine use of prophylactic dexamethasone in uninfected patients, to avoid inducing lymphopenia, which may increase risk of infection or lead to inferior outcomes if a cancer patient subsequently becomes infected. Since many cancer drugs and malignant diseases inherently cause lymphopenia, further reduction of lymphocytes with dexamethasone should be avoided if possible and if safe and effective alternative antiemetics are available during the COVID-19 crisis.", "qid": 46, "docid": "pec5ezyy", "rank": 28, "score": 7.118100166320801}, {"content": "Title: Glucocorticoids inhibit neurogenic plasma extravasation and prevent virus-potentiated extravasation in the rat trachea. Content: Capsaicin increases the permeability of blood vessels in the rat tracheal mucosa through a mechanism involving the release of tachykinins from sensory nerves. This capsaicin-induced increase in vascular permeability is potentiated by viral infections of the respiratory tract. The present study was done to determine whether this \"neurogenic plasma extravasation\" can be inhibited by glucocorticoids, to learn the time course of this inhibition, and to determine whether glucocorticoids can prevent the potentiating effect of viral respiratory infections on neurogenic plasma extravasation. Groups of pathogen-free F344 rats were treated with dexamethasone for 2 or 8 h (4 mg/kg i.p.) or 48 or 120 h (0.5-4 mg/kg per d i.p.). Another group of rats was treated with dexamethasone for 120 h following the intranasal inoculation of Sendai virus. The magnitude of plasma extravasation produced by capsaicin or substance P was assessed after this treatment by using Monastral blue pigment and Evans blue dye as intravascular tracers. We found that dexamethasone reduced, in a dose-dependent fashion, the magnitude of plasma extravasation produced in the rat trachea by capsaicin and substance P. Significant inhibition was produced by a dose of dexamethasone as small as 0.5 mg/kg i.p. The effect of dexamethasone had a latency of several hours and reached a maximum after 2 d of treatment. Furthermore, dexamethasone prevented the potentiation of neurogenic plasma extravasation usually present after 5 d of Sendai virus respiratory infection.", "qid": 46, "docid": "qxlz1ff6", "rank": 29, "score": 7.107900142669678}, {"content": "Title: Dexamethasone attenuated endotoxin-induced acute lung injury through inhibiting expression of inducible nitric oxide synthase. Content: Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.", "qid": 46, "docid": "lkud2lbv", "rank": 30, "score": 7.0183000564575195}, {"content": "Title: The use of dexamethasone in the treatment of COVID-19 Content:", "qid": 46, "docid": "tw3luwll", "rank": 31, "score": 7.006899833679199}, {"content": "Title: Low-dose radiation therapy for COVID-19 pneumopathy: what is the evidence? Content: In the current dismal situation of the COVID-19 pandemic, effective management of patients with pneumonia and acute respiratory distress syndrome is of vital importance. Due to the current lack of effective pharmacological concepts, this situation has caused interest in (re)considering historical reports on the treatment of patients with low-dose radiation therapy for pneumonia. Although these historical reports are of low-level evidence per se, hampering recommendations for decision-making in the clinical setting, they indicate effectiveness in the dose range between 0.3 and 1 Gy, similar to more recent dose concepts in the treatment of acute and chronic inflammatory/degenerative benign diseases with, e.g., a single dose per fraction of 0.5 Gy. This concise review aims to critically review the evidence for low-dose radiation treatment of COVID-19 pneumopathy and discuss whether it is worth investigating in the present clinical situation.", "qid": 46, "docid": "bheq9p5w", "rank": 32, "score": 6.998300075531006}, {"content": "Title: Low-dose radiation therapy for COVID-19 pneumopathy: what is the evidence? Content: In the current dismal situation of the COVID-19 pandemic, effective management of patients with pneumonia and acute respiratory distress syndrome is of vital importance. Due to the current lack of effective pharmacological concepts, this situation has caused interest in (re)considering historical reports on the treatment of patients with low-dose radiation therapy for pneumonia. Although these historical reports are of low-level evidence per se, hampering recommendations for decision-making in the clinical setting, they indicate effectiveness in the dose range between 0.3 and 1\u00e2\u0080\u00afGy, similar to more recent dose concepts in the treatment of acute and chronic inflammatory/degenerative benign diseases with, e.g., a single dose per fraction of 0.5\u00e2\u0080\u00afGy. This concise review aims to critically review the evidence for low-dose radiation treatment of COVID-19 pneumopathy and discuss whether it is worth investigating in the present clinical situation.", "qid": 46, "docid": "o07stuxw", "rank": 33, "score": 6.9982991218566895}, {"content": "Title: Receptor-mediated induction of human dermal fibroblast ectoaminopeptidase N by glucocorticoids Content: Aminopeptidase N was demonstrated in human dermal fibroblasts as an ectoenzyme. The enzyme has wide substrate specificity, with a K (m) of 0.63 mM and V (max) of 338 nmol min(\u22121) mg(\u22121). Addition of fetal calf serum to the culture medium increased aminopeptidase N activity up to 63% by 10% serum in a 48-h culture. Treatment of fibroblasts by dexamethasone increased ectoaminopeptidase N activity in a dose- and time-dependent manner. Maximal increase of aminopeptidase N occurred after treatment with 1 \u03bcM dexamethasone for 3 days. Actinomycin D, a blocker of RNA synthesis, and cycloheximide, an inhibitor of protein synthesis, did not alter basal aminopeptidase N activity. However, they prevented stimulation by dexamethasone. RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone-induced increase in aminopeptidase N activity. This study shows that human dermal fibroblasts contain ectoaminopeptidase N controlled by glucocorticoids through a receptor-mediated mechanism.", "qid": 46, "docid": "lsrdk9ap", "rank": 34, "score": 6.962699890136719}, {"content": "Title: Management of non traumatic surgical emergencies during the COVID-19 pandemia Content: In December 2019, in Wuhan, China, the first cases of what would be known as COVID-19, a disease caused by an RNA virus called SARS-CoV-2, were described Its spread was rapid and wide, leading the World Health Organization to declare a pandemic in March 2020 The disease has distinct clinical presentations, from asymptomatic to critical cases, with high lethality Parallel to this, patients with non-traumatic surgical emergencies, such as acute appendicitis and cholecystitis, continue to be treated at the emergency services In this regard, there were several doubts on how to approach these cases, among them: how to quickly identify the patient with COVID-19, what is the impact of the abdominal surgical disease and its treatment on the evolution of patients with COVID-19, in addition to the discussion about the role of the non-operative treatment for abdominal disease under these circumstances In this review, we discuss these problems based on the available evidence", "qid": 46, "docid": "vnq1fjwy", "rank": 35, "score": 6.945700168609619}, {"content": "Title: Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.", "qid": 46, "docid": "okrpa7k7", "rank": 36, "score": 6.927800178527832}, {"content": "Title: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19 Content: Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it\u2019s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government\u2019s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians\u2019 attitudes? Finally, what are the government, physicians, and patient\u2019s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government\u2019s, practitioner\u2019s and patient\u2019s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.", "qid": 46, "docid": "rffp6qe2", "rank": 37, "score": 6.907899856567383}, {"content": "Title: A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave? Content: If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, \u201cmiraculous cures\u201d, psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop \u201cdynamic\u201d indications able to fight such an unpredictable pandemic.", "qid": 46, "docid": "3mvjc805", "rank": 38, "score": 6.905399799346924}, {"content": "Title: A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave? Content: If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, \"miraculous cures\", psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop \"dynamic\" indications able to fight such an unpredictable pandemic.", "qid": 46, "docid": "xzcxehui", "rank": 39, "score": 6.905398845672607}, {"content": "Title: Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons Content: BACKGROUND: Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. METHODS: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. RESULTS: Dexamethasone-immunosuppressed male mice (6\u20138 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had \u2265 10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45 + and CD8 + inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). CONCLUSIONS: Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.", "qid": 46, "docid": "v4r5d26a", "rank": 40, "score": 6.895299911499023}, {"content": "Title: Comparison of dexmedetomidine and dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Content: BACKGROUND Postoperative nausea and vomiting (PONV) are common following laparoscopic cholecystectomy (LC). Dexamethasone has been reported to reduce PONV. However, there is insufficient evidence regarding the effect of dexmedetomidine in decreasing PONV. This study was designed to compare the effects of a single dose of dexmedetomidine to dexamethasone for reducing PONV after LC. METHODS Eighty-six adult patients scheduled for LC were randomized to receive either single dose 1 \u00b5g/kg of dexmedetomidine (Dexmed group, N = 43) or 8 mg dexamethasone (Dexa group, N = 43) before skin incision. During the first 24 h postoperatively, the incidence and severity of PONV were assessed. Pain and sedation scores were assessed on arrival in the recovery room and early postoperatively. Analgesic and antiemetic consumption during the 24 h after surgery were calculated. Intra-operative and postoperative hemodynamics were recorded. RESULTS Twenty-one percent of the patients in the Dexmed group developed PONV compared to 28% in the Dexa group (P = 0.6). Severity of PONV was similar between the two groups (P = 0.07). Early postoperatively, pain severity was significantly lower in the Dexmed group, but sedation scores were significantly higher. The first analgesic request was significantly delayed in the Dexmed group (P = 0.02). The total amounts of intraoperative fentanyl and postoperative tramadol administered were significantly lower in the Dexmed group. No difference in ondansetron was noted between the two groups. Mean arterial pressure and heart rate were significantly lower in the Dexmed group after administration of dexmedetomidine. No major side effects were reported. CONCLUSIONS Dexmedetomidine reduces the incidence and severity of PONV, similar to dexamethasone. It is superior to dexamethasone in reducing postoperative pain and total analgesic consumption during the first 24 h after LC.", "qid": 46, "docid": "lliix0hj", "rank": 41, "score": 6.879899978637695}, {"content": "Title: Transcatheter drug delivery through bronchial artery for COVID-19: is it fiction or could it come true? Content: More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise for treatment of COVID-19. Nevertheless, up to date, no drugs have been confirmed as a definitive treatment for COVID-19. Trials such as the SOLIDARITY and RECOVERY are ongoing, and first results were announced in favour of therapy with dexamethasone with a significant trend showing greatest benefit among those patients requiring ventilation. The drawbacks of these trials include exposing the patients to drugs with well-documented systemic adverse effects or unknown complications of novel therapies without proof of clinical benefit. We present here the hypothesis that bronchial artery infusion could be an alternative for systemic drug infusion in COVID-19 trials with superadded benefits of high drug concentration and low systemic adverse effects. The concept of this idea has many uncertainties and no current clinical data to support. Perhaps, the technique should be first applied in animal models to determine its safety and calculate the effective dose of the drugs. Guidelines and reviews of pharmacotherapy for COVID-19 should be implemented for this fiction to come true.", "qid": 46, "docid": "ylcaw0vi", "rank": 42, "score": 6.7571001052856445}, {"content": "Title: Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. Content: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.", "qid": 46, "docid": "5hei9fac", "rank": 43, "score": 6.730400085449219}, {"content": "Title: Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review Content: Importance: The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations: SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance: As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.", "qid": 46, "docid": "j8q6n9cs", "rank": 44, "score": 6.730399131774902}, {"content": "Title: Pharmacologicaltreatment of COVID-19: lights and shadows Content: At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.", "qid": 46, "docid": "o29773cz", "rank": 45, "score": 6.724800109863281}, {"content": "Title: Evidence based management guideline for the COVID-19 pandemic - Review article Content: COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 2.5 million people worldwide, resulting in over 170,000 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.", "qid": 46, "docid": "2697ts31", "rank": 46, "score": 6.70959997177124}, {"content": "Title: Evidence Based Management Guideline for the COVID-19 Pandemic - Review article Content: ABSTRACT COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.", "qid": 46, "docid": "ver7x3lx", "rank": 47, "score": 6.709599018096924}, {"content": "Title: COVID-19 y el sistema renina, angiotensina, aldosterona. Una relaci\u00f3n compleja./ COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.", "qid": 46, "docid": "2vns1wdb", "rank": 48, "score": 6.654300212860107}, {"content": "Title: COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship. Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.", "qid": 46, "docid": "l8flafv4", "rank": 49, "score": 6.644999980926514}, {"content": "Title: COVID-19 y el sistema renina, angiotensina, aldosterona. Una relaci\u00f3n compleja Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications This review reports current knowledge on the relationship between COVID-19 and SRAA", "qid": 46, "docid": "oweh98z2", "rank": 50, "score": 6.644999027252197}, {"content": "Title: Clinical interventions for severe and critical COVID-19: What are the options Content: The coronavirus disease 2019 (COVID-19) has been ongoing outbreak and declared as a global public health emergency by the World Health Organization Severe and critical COVID-19 has high fatality rate due to complications like acute respiratory distress syndrome, acute respiratory failure or multiple organ failure So far, there have been mounting research on the epidemiological and clinical characteristics of COVID-19 However, the information regarding treatment of severe and critical COVID-19 is limited The current study reviewed published evidence of clinical interventions of severe and critical COVID-19, aiming to provide an up-to-date reference for further clinical treatment", "qid": 46, "docid": "3aam2j5z", "rank": 51, "score": 6.625199794769287}, {"content": "Title: Clinical interventions for severe and critical COVID-19: what are the options. Content: The coronavirus disease 2019 (COVID-19) has been ongoing outbreak and declared as a global public health emergency by the World Health Organization. Severe and critical COVID-19 has high fatality rate due to complications like acute respiratory distress syndrome, acute respiratory failure or multiple organ failure. So far, there have been mounting research on the epidemiological and clinical characteristics of COVID-19. However, the information regarding treatment of severe and critical COVID-19 is limited. The current study reviewed published evidence of clinical interventions of severe and critical COVID-19, aiming to provide an up-to-date reference for further clinical treatment.", "qid": 46, "docid": "si37zgkl", "rank": 52, "score": 6.625198841094971}, {"content": "Title: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say? Content: There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.", "qid": 46, "docid": "zpb9jicw", "rank": 53, "score": 6.597599983215332}, {"content": "Title: Evidence-based medicine and COVID-19: what to believe and when to change. Content: The COVID-19 pandemic has led to a surge of information being presented to clinicians regarding this novel and deadly disease. There is a clear urgency to collate, review, appraise and act on this information if we are to do the best for clinicians and patients. However, the speed of the pandemic is a threat to traditional models of knowledge translation and practice change. In this concepts paper, we argue that clinicians need to be agile in their thinking and practice in order to find the right time to change. Adoption of new methods should be based on clinical judgement, the weight of evidence and the balance of probabilities that any new technique, test or treatment might work. The pandemic requires all of us to reach a new level of evidence-based medicine characterised by scepticism, thoughtfulness, responsiveness and clinically agility in practice.", "qid": 46, "docid": "a9yscv8v", "rank": 54, "score": 6.512199878692627}, {"content": "Title: Evidence-based medicine and COVID-19: what to believe and when to change Content: The COVID-19 pandemic has led to a surge of information being presented to clinicians regarding this novel and deadly disease. There is a clear urgency to collate, review, appraise and act on this information if we are to do the best for clinicians and patients. However, the speed of the pandemic is a threat to traditional models of knowledge translation and practice change. In this concepts paper, we argue that clinicians need to be agile in their thinking and practice in order to find the right time to change. Adoption of new methods should be based on clinical judgement, the weight of evidence and the balance of probabilities that any new technique, test or treatment might work. The pandemic requires all of us to reach a new level of evidence-based medicine characterised by scepticism, thoughtfulness, responsiveness and clinically agility in practice.", "qid": 46, "docid": "l64pg7pg", "rank": 55, "score": 6.5121989250183105}, {"content": "Title: COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments Content: Scientists hypothesized that drugs such as ibuprofen or renin-angiotensin system (RAS) blockers could exacerbate the novel coronavirus disease COVID-19 by upregulating the angiotensin-converting enzyme 2 (ACE2), which serves as an entry receptor for the coronavirus SARS-CoV-2. This hypothesis was taken up by the lay press and led to concerns among doctors and patients whether the use of these drugs was still safe and justified against the background of the pandemic spread of SARS-CoV-2 with an increasing number of cases and deaths. In this article, we summarize what is known about the effect of RAS blockers or non-steroidal anti-inflammatory drugs (NSAIDs) on the course of COVID-19 disease. In the case of RAS inhibition, we also find evidence for the opposite hypothesis, namely, that RAS inhibition in COVID-19 could be protective. In view of the inconsistent and limited evidence and after weighing up the benefits and risks, we would not currently recommend discontinuing or switching an effective treatment with RAS blockers. NSAIDs should be used at the lowest effective dose for the shortest possible period. The choice of drug to treat COVID-19-associated fever or pain should be based on a benefit-risk assessment for known side effects (e.g., kidney damage, gastrointestinal ulceration).", "qid": 46, "docid": "s8b4j0j2", "rank": 56, "score": 6.495200157165527}, {"content": "Title: A Contemporary Review of Neurological Sequelae of COVID-19 Content: Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a \u201ccytokine storm\u201d can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.", "qid": 46, "docid": "411qyubx", "rank": 57, "score": 6.492000102996826}, {"content": "Title: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study Content: COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.", "qid": 46, "docid": "fbm3zoe2", "rank": 58, "score": 6.480299949645996}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 46, "docid": "x82yaoxc", "rank": 59, "score": 6.4475998878479}, {"content": "Title: Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN) Content: Patients with multiple myeloma (MM) seem to be at increased risk for more severe COVID-19 infection and associated complications due to their immunocompromised state, the older age and comorbidities. The European Myeloma Network has provided an expert consensus statement in order to guide therapeutic decisions in the era of the COVID-19 pandemic. Patient education for personal hygiene and social distancing measures, along with treatment individualization, telemedicine and continuous surveillance for early diagnosis of COVID-19 are essential. In countries or local communities where COVID-19 infection is widely spread, MM patients should have a PCR test of nasopharyngeal swab for SARS-CoV-2 before hospital admission, starting a new treatment line, cell apheresis or ASCT in order to avoid ward or community spread and infections. Oral agent-based regimens should be considered, especially for the elderly and frail patients with standard risk disease, whereas de-intensified regimens for dexamethasone, bortezomib, carfilzomib and daratumumab should be used based on patient risk and response. Treatment initiation should not be postponed for patients with end organ damage, myeloma emergencies and aggressive relapses. Autologous (and especially allogeneic) transplantation should be delayed and extended induction should be administered, especially in standard risk patients and those with adequate MM response to induction. Watchful waiting should be considered for standard risk relapsed patients with low tumor burden, and slow biochemical relapses. The conduction of clinical trials should continue with appropriate adaptations to the current circumstances. Patients with MM and symptomatic COVID-19 disease should interrupt anti-myeloma treatment until recovery. For patients with positive PCR test for SARS-CoV-2, but with no symptoms for COVID-19, a 14-day quarantine should be considered if myeloma-related events allow the delay of treatment. The need for surveillance for drug interactions due to polypharmacy is highlighted. The participation in international COVID-19 cancer registries is greatly encouraged.", "qid": 46, "docid": "u9u5jcp0", "rank": 60, "score": 6.447400093078613}, {"content": "Title: Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice. Content: Glucocorticoids are widely used in the treatment of different inflammatory diseases. The present study was performed to investigate the effect of dexamethasone (DEX) on acute respiratory distress syndrome (ARDS) induced by the H5N1 viral infection in mice. BALB/c mice, 6-8 weeks old, were divided into three groups with 80 mice in each. The infected group and the DEX-treated infected group were inoculated intranasally with 1 x 10(2) 50% mouse infectious dose of A/Chicken/Hebei/108/2002 (H5N1) viruses, with daily intraperitoneal injections of PBS, or 2.5 mg.kg(-1) DEX at days 3-14 post inoculation, respectively. The control group received noninfectious allantoic fluid and a daily intraperitoneal injection of PBS. In H5N1-infected mice, DEX treatment did not improve the mortality (17 out of 20 versus 16 out of 20 deaths in the DEX-treated infected group versus the infected group), and did not alleviate clinical signs, including weight loss, decreased food intake and inactivity. There was no significant amelioration of the hypoxaemia and ARDS-associated pathological changes in DEX-treated infected mice, as assessed by blood gas analysis and histological score. Furthermore, DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release (interleukin-6 and tumour necrosis factor-alpha) in bronchoalveolar lavage fluid induced by the H5N1 infection. In conclusion, dexamethasone treatment (2.5 mg.kg(-1)) from days 3-14 post inoculation has no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection in mice.", "qid": 46, "docid": "xrvgpd67", "rank": 61, "score": 6.4375}, {"content": "Title: What is the impact of COVID-19 on head and neck squamous cell carcinoma patients? Content: Data sources It is not made clear in this review the different databases selected or how they conducted their search. The studies used are from 1975-2020Study selection The authors have performed a scoping review using 84 studies ranging from 1975-2020. The majority of these are from before the 2019-2020 COVID-19 outbreak period. This is indicative of the lack of evidence on this topic and exemplifies why a scoping review was carried out rather than a systematic review. The studies that were reviewed were predominately cohort and case studies. With regards to previous treatment outcomes, a few systematic reviews were included, but again, the novel nature of this outbreak means that largely, there are only cohort or case studies available for review.Data extraction and synthesis There are ten authors, with no indication of how many performed the literature review or if a mediator was involved in the final decision making on what papers would be reviewed.Results Excessive consumption of alcohol, history of tobacco use, an ageing population, and comorbidities such as cardiopulmonary issues are substantial risk factors for episodes of unfavourable respiratory outcomes. The risk of these outcomes is increased by some of the toxic effects of treatments such as chemotherapy or radiotherapy.Conclusions The COVID-19 outbreak has a potentially disproportionate impact on the cohort of head and neck cancer patients, and the respiratory effects this has on these patients may increase morbidity and mortality. It is important to include alcohol and smoking cessation, along with good oral hygiene instruction in the care of these patients.", "qid": 46, "docid": "hekzjb3f", "rank": 62, "score": 6.406400203704834}, {"content": "Title: What is the impact of COVID-19 on head and neck squamous cell carcinoma patients? Content: Data sources It is not made clear in this review the different databases selected or how they conducted their search. The studies used are from 1975-2020 Study selection The authors have performed a scoping review using 84 studies ranging from 1975-2020. The majority of these are from before the 2019-2020 COVID-19 outbreak period. This is indicative of the lack of evidence on this topic and exemplifies why a scoping review was carried out rather than a systematic review. The studies that were reviewed were predominately cohort and case studies. With regards to previous treatment outcomes, a few systematic reviews were included, but again, the novel nature of this outbreak means that largely, there are only cohort or case studies available for review. Data extraction and synthesis There are ten authors, with no indication of how many performed the literature review or if a mediator was involved in the final decision making on what papers would be reviewed. Results Excessive consumption of alcohol, history of tobacco use, an ageing population, and comorbidities such as cardiopulmonary issues are substantial risk factors for episodes of unfavourable respiratory outcomes. The risk of these outcomes is increased by some of the toxic effects of treatments such as chemotherapy or radiotherapy. Conclusions The COVID-19 outbreak has a potentially disproportionate impact on the cohort of head and neck cancer patients, and the respiratory effects this has on these patients may increase morbidity and mortality. It is important to include alcohol and smoking cessation, along with good oral hygiene instruction in the care of these patients.", "qid": 46, "docid": "vpxubnkc", "rank": 63, "score": 6.406399250030518}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: Background: This study\u2019s aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \u201cWhat are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\u201d Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 46, "docid": "irocv0ke", "rank": 64, "score": 6.402599811553955}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: BACKGROUND: This study's aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. METHODS: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \"What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\" RESULTS: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. CONCLUSIONS: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 46, "docid": "o7ze1myf", "rank": 65, "score": 6.402598857879639}, {"content": "Title: Repurposing drugs for COVID-19 based on transcriptional response of host cells to SARS-CoV-2 Content: The Coronavirus Disease 2019 (COVID-19) pandemic has infected over 10 million people globally with a relatively high mortality rate. There are many therapeutics undergoing clinical trials, but there is no effective vaccine or therapy for treatment thus far. After affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), molecular signaling of host cells plays critical roles during the life cycle of SARS-CoV-2. Thus, it is significant to identify the involved molecular signaling pathways within the host cells, and drugs targeting these molecular signaling pathways could be potentially effective for COVID-19 treatment. In this study, we aimed to identify these potential molecular signaling pathways, and repurpose existing drugs as a potentially effective treatment of COVID-19 to facilitate the therapeutic discovery, based on the transcriptional response of host cells. We first identified dysfunctional signaling pathways associated with the infection caused SARS-CoV-2 in human lung epithelial cells through analysis of the altered gene expression profiles. In addition to the signaling pathway analysis, the activated gene ontologies (GOs) and super gene ontologies were identified. Signaling pathways and GOs such as MAPK, JNK, STAT, ERK, JAK-STAT, IRF7-NFkB signaling, and MYD88/CXCR6 immune signaling were particularly identified. Based on the identified signaling pathways and GOs, a set of potentially effective drugs were repurposed by integrating the drug-target and reverse gene expression data resources. The dexamethasone was top-ranked in the prediction, which was the first reported drug to be able to significantly reduce the death rate of COVID-19 patients receiving respiratory support. The results can be helpful to understand the associated molecular signaling pathways within host cells, and facilitate the discovery of effective drugs for COVID-19 treatment.", "qid": 46, "docid": "h04lnb8y", "rank": 66, "score": 6.390100002288818}, {"content": "Title: Pulmonary Capillary Leak Syndrome following COVID\u201019 Virus Infection Content: Pulmonary capillary leak syndrome secondary to influenza SARS\u2010CoV\u20102virus infection was not previously reported. We report 2 cases. The diagnosis of non\u2010cardiogenic pulmonary edema due to pulmonary capillary leak syndrome SARS\u2010CoV\u20102 virus infection was obtained by a medical committee of 6 physicians. The diagnosis of COVID\u201019 infection is confirmed by reverse transcription polymerase chain reaction (RT\u2010PCR) test. Moreover, in this specific endemic situation, and according to the British Society of Thoracic Imaging expert reference group update, we took account of chest CT\u2010Scan results in the early detection of COVID\u201019 pneumonia. Our 2 patients with a confirmed influenza SARS\u2010CoV\u20102virus infection had respiratory distress with lung crackles on auscultation of one or both lungs and with alveolar pulmonary edema on the chest CT\u2010Scan. The cardiogenic nature of pulmonary edema was ruled out in both cases by a transthoracic echocardiography showing normal systolic and diastolic functions. Our patients were treated by oxygen via face mask in one case and mechanical ventilation as supportive treatment in the other patient. Hydroxychloroquine (600mg/day), Azithromycine, steroids (dexamethasone 20mg/day), vitamin C (3g/day), Zinc, diuretics and Enoxaparine were equally used for the two patients. Evolution was marked by a good outcome in both of them. In summary, acute respiratory failure is a rare but major complication of COVID\u201019 virus infection. It is due to pulmonary capillary leak syndrome. Treatment is based on a good oxygenation, intravenous corticosteroids, diuretics, Azithromycine, vitamin C, and other symptomatic treatments. This article is protected by copyright. All rights reserved.", "qid": 46, "docid": "e5fh7r7a", "rank": 67, "score": 6.358099937438965}, {"content": "Title: COVID-19 and Headache: A Primer for Trainees Content: OBJECTIVE: To summarize for the trainee audience the possible mechanisms of headache in patients with COVID-19 as well as to outline the impact of the pandemic on patients with headache disorders and headache medicine in clinical practice. BACKGROUND: COVID-19 is a global pandemic caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, of which a large subset of patients features neurological symptoms, commonly headache. The virus is highly contagious and is, therefore, changing clinical practice by forcing limitations on in-person visits and procedural treatments, more quickly shifting toward the widespread adaptation of telemedicine services. DESIGN/RESULTS: We review what is currently known about the pathophysiology of COVID-19 and how it relates to possible mechanisms of headache, including indirect, potential direct, and secondary causes. Alternative options for the treatment of patients with headache disorders and the use of telemedicine are also explored. CONCLUSIONS: Limited information exists regarding the mechanisms and timing of headache in patients with COVID-19, though causes relate to plausible direct viral invasion of the nervous system as well as the cytokine release syndrome. Though headache care in the COVID-19 era requires alterations, the improved preventive treatment options now available and evidence for feasibility and safety of telemedicine well positions clinicians to take care of such patients, especially in the COVID-19 epicenter of New York City.", "qid": 46, "docid": "kre0npli", "rank": 68, "score": 6.33050012588501}, {"content": "Title: Patients with specific skin disorders who are affected by COVID-19: What do experiences say about management strategies? A systematic review Content: In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection), and the most proper management strategies include both issues that are what this systematic review targets. Databases of PubMed, Scopus, Google Scholar, Medscape, and Centre of Evidence-Based Dermatology, coronavirus dermatology resource of Nottingham University searched completely up to May 15, 2020, and initial 237 articles were selected to further review and finally 9 articles (including 12 patients) entered to this study. From 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only 1 patient required Intensive Care Unit admission, the others have been treated for mild-moderate symptoms with conventional therapies. The biologic or immunosuppressive/immunomodulator agents have been ceased during the course of disease. The course of coronovirus diseases 2019 (COVID-19) and its management was as similar as normal populations. Their underlying dermatologic disease were exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. Exacerbation of patients underlying dermatologic disease was mild to moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence and disturbing cytokine storms in these patients.", "qid": 46, "docid": "x96vp6r4", "rank": 69, "score": 6.31790018081665}, {"content": "Title: Managing Patients with Multiple Myeloma during the COVID-19 Pandemic: Recommendations from an Expert Panel - ABHH Monoclonal Gammopathies Committe Content: Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.", "qid": 46, "docid": "kh15qvv8", "rank": 70, "score": 6.298999786376953}, {"content": "Title: Managing Patients with Multiple Myeloma during the COVID-19 Pandemic: Recommendations from an Expert Panel \u2013 ABHH Monoclonal Gammopathies Committe Content: Abstract Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.", "qid": 46, "docid": "pwxprzha", "rank": 71, "score": 6.298998832702637}, {"content": "Title: Low frequency of CD3(+)CD4(+)CD161(+) T cells correlates with the occurrence of infections in refractory/relapsed multiple myeloma patients receiving lenalidomide plus low-dose dexamethasone treatment Content: The aim of this study was to explore the predictive implications of the composition of immune cell populations prior to lenalidomide plus high-dose dexamethasone (Len-Dex) initiation for the occurrence of infections. We prospectively examined immune cell populations in peripheral blood taken at baseline of lenalidomide plus low-dose dexamethasone (Len-dex) therapy and reviewed clinical and microbiology records in 90 patients with refractory/relapsed multiple myeloma (RRMM). Risk factors for infection were analyzed using logistic regression. During a median of 11 cycles of Len-dex treatment, 52 (57.8%) patients experienced at least 1 infection episode. Of a total of 92 episodes of infection, 58 (63%) episodes were clinically defined, 29 (31.5%) episodes were microbiologically defined, and 5 (5.4%) episodes were fever of unknown origin. Severe episodes were more frequently observed during the first 3 cycles. After adjusting for risk factors for infection based on univariate analyses, multivariate analyses showed that lower Hb (< 10 g/dL) was a clinically independent factor associated with occurrence of infections. Lower frequency (P = 0.044) and absolute count (P = 0.014) of circulating CD3(+)CD4(+)CD161(+) cells prior to Len-dex treatment were also associated with the occurrence of infection, especially during the first 3 cycles of Len-dex therapy. In addition to several clinical predictive factors, we found that CD3(+)CD4(+)CD161(+) cells may provide additional information for predicting the occurrence of infection in the early period of Len-dex therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-018-3401-y) contains supplementary material, which is available to authorized users.", "qid": 46, "docid": "z1lvq0iv", "rank": 72, "score": 6.291500091552734}, {"content": "Title: Decreased expression of type I (IFN-\u03b2) and type III (IFN-\u03bb) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps Content: Background Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.", "qid": 46, "docid": "wbyw2lrq", "rank": 73, "score": 6.275400161743164}, {"content": "Title: The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Content: BACKGROUND The pattern and magnitude of the hyperglycemic response to surgical stress, the added effect of low-dose steroids, and whether these differ in diabetics and nondiabetics remain unclear. We therefore tested 2 hypotheses: (1) that diabetics show a greater increase from preoperative to intraoperative glucose concentrations than nondiabetics; and (2) that steroid administration increases intraoperative hyperglycemia more so in diabetics compared with nondiabetics. METHODS Patients scheduled for major noncardiac surgery under general anesthesia were enrolled and randomized to preoperative IV 8 mg dexamethasone or placebo, stratified by diagnosis of diabetes. Patients were part of a larger underlying trial (the Dexamethasone, Light Anesthesia and Tight Glucose Control [DeLiT] Trial). IV insulin was given when glucose concentration exceeded 215 mg/dL. The primary outcome measure was the change in glucose from the preoperative to maximal intraoperative glucose concentration. We also report the time-dependent pattern of intraoperative hyperglycemia. RESULTS Ninety patients (23% with diabetes) were randomized to dexamethasone, and 95 (29% with diabetes) were given placebo. The mean \u00b1 SD change from preoperative to maximal intraoperative glucose concentration was 63 \u00b1 69 mg/dL in diabetics and 72 \u00b1 45 mg/dL in nondiabetics. The mean covariable-adjusted change (95% confidence interval) in nondiabetics was 29 (13, 46) mg/dL more than in diabetics (P < 0.001). For all patients combined, mean glucose increased slightly from preoperative to incision, substantially from incision to surgery midpoint, and then remained high and fairly stable through emergence, with nondiabetic patients showing a greater increase (P < 0.001). For nondiabetics, the mean increase in glucose concentration (97.5% CI) was 29 (9, 49) mg/dL more in patients given dexamethasone than placebo (P = 0.0012). However, there was no dexamethasone effect in diabetics (P = 0.99). CONCLUSIONS Treatment of intraoperative hyperglycemia should account for the hyperglycemic surgical stress response trend depending on the stage of surgery as well as the added effects of steroid administration. Denying steroid prophylaxis for postoperative nausea and vomiting for fear of hyperglycemic response should be reconsidered given the limited effect of steroids on intraoperative blood glucose concentrations.", "qid": 46, "docid": "oh67pq5f", "rank": 74, "score": 6.254799842834473}, {"content": "Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "qid": 46, "docid": "b6aeu1ph", "rank": 75, "score": 6.236499786376953}, {"content": "Title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Content: The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.", "qid": 46, "docid": "l6l24pco", "rank": 76, "score": 6.195099830627441}, {"content": "Title: Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain. Content: Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.", "qid": 46, "docid": "ix9x25sc", "rank": 77, "score": 6.184100151062012}, {"content": "Title: Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain Content: Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.", "qid": 46, "docid": "qzxvh2qc", "rank": 78, "score": 6.184099197387695}, {"content": "Title: A Randomized, Double-blind, Non-inferiority Trial of Magnesium Sulphate versus Dexamethasone for Prevention of Postoperative Sore Throat after Lumbar Spinal Surgery in the Prone Position. Content: BACKGROUND Postoperative sore throat (POST) is a frequent complication of tracheal intubation, particularly after surgery in the prone position. We designed this study to validate the non-inferiority of magnesium sulphate against dexamethasone for prevention of POST after lumbar spinal surgery. METHODS One hundred and forty-six patients were randomly allocated to receive either magnesium or dexamethasone. Before anesthetic induction, the magnesium group (n = 73) received magnesium sulphate 30 mg/kg followed by 10 mg/kg/h by continuous infusion until the end of surgery. The dexamethasone group (n = 73) received dexamethasone 8 mg. The primary endpoint was the overall incidence of POST, which was assessed serially over 48 hr postoperatively. The predefined margin of non-inferiority for magnesium against dexamethasone was 15%. RESULTS Overall incidences of POST at rest (50.7% versus 49.3% in the magnesium and dexamethasone group, respectively, p = 0.869) and swallowing (65.8% versus 61.6% in the magnesium and dexamethasone group, respectively, p = 0.606) were not different between the groups. The upper limit of the 90% confidence interval, which must be lower than the predefined margin of non-inferiority to prove the non-inferiority of magnesium sulphate against dexamethasone, for at rest and swallowing were 14.97% (p = 0.0496) and 17.19% (p = 0.0854), respectively. The incidences and severities of POST and hoarseness were also not different between the groups throughout the study period. CONCLUSIONS Prophylactic magnesium sulphate appears to be non-inferior to dexamethasone for the prevention of POST at rest in patients undergoing lumbar spinal surgery in the prone position.", "qid": 46, "docid": "k7znamun", "rank": 79, "score": 6.183499813079834}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID\u201019 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID\u201019). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID\u201019 are treated with these agents and more evidence accumulates, there continues to be no high\u2010quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto\u2010immune conditions, and provided a component in the original rationale for their use in patients with COVID\u201019, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID\u201019. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID\u201019, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID\u201019 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case\u2010by\u2010case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 46, "docid": "75vvix5o", "rank": 80, "score": 6.179800033569336}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID-19 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 46, "docid": "87uhx3pt", "rank": 81, "score": 6.1797990798950195}, {"content": "Title: Complicated Grief: What to Expect After the Coronavirus Pandemic Content: The COVID-19 pandemic is one of the worst public health crises in a century, with an expected amount of deaths of several million worldwide and an even bigger number of bereaved people left behind. Although the consequences of this crisis are still unknown, a significant number of bereaved people will arguably develop Complicated Grief (CG) in the aftermath of this emergency. If the current pandemic is unprecedented, the grief following the coronavirus outbreak is likely to share features with grief related to natural disasters and after Intensive Care Unit (ICU) treatment. The aim of this paper is to review the most prominent literature on CG after natural disasters, as well as after diseases requiring ICU treatment. This body of evidence may be useful for helping bereaved people during the acute phase of the COVID-19 pandemic and for drawing clinical attention to people at risk for CG.", "qid": 46, "docid": "h1tulk56", "rank": 82, "score": 6.1682000160217285}, {"content": "Title: Coronavirus disease (COVID\u201019) and neonate: What neonatologist need to know Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS\u2010CoV\u20102 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID\u201019) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID\u201019 infection in newborns and children.", "qid": 46, "docid": "1hwcp09t", "rank": 83, "score": 6.1666998863220215}, {"content": "Title: Coronavirus disease (COVID-19) and neonate: What neonatologist need to know Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.", "qid": 46, "docid": "4qy35wdf", "rank": 84, "score": 6.166698932647705}, {"content": "Title: Coronavirus disease 2019: What we know? Content: In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID-19) by the World Health Organization, respectively. The COVID-19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID-19, but also to comment briefly on the epidemiology and pathology based on the current evidence.", "qid": 46, "docid": "ofuzk4by", "rank": 85, "score": 6.166697978973389}, {"content": "Title: Coronavirus disease 2019: What we know? Content: In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID\u201019) by the World Health Organization, respectively. The COVID\u201019 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID\u201019, but also to comment briefly on the epidemiology and pathology based on the current evidence.", "qid": 46, "docid": "qpcvxwti", "rank": 86, "score": 6.166697025299072}, {"content": "Title: Repurpose Open Data to Discover Therapeutics for COVID-19 using Deep Learning. Content: There have been more than 2.2 million confirmed cases and over 120,000 deaths from the human coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), in the United States alone. However, there are currently lack of proven effective medications against COVID-19. Drug repurposing offers a promising way for the development of prevention and treatment strategies for COVID-19. This study reports an integrative, network-based deep learning methodology to identify repurposable drugs for COVID-19 (termed CoV-KGE). Specifically, we built a comprehensive knowledge graph that includes 15 million edges across 39 types of relationships connecting drugs, diseases, proteins/genes, pathways, and expression, from a large scientific corpus of 24 million PubMed publications. Using Amazon's AWS computing resources and a network-based, deep learning framework, we identified 41 repurposable drugs (including dexamethasone, indomethacin, niclosamide, and toremifene) whose therapeutic association with COVID-19 were validated by transcriptomic and proteomic data in SARS-CoV-2 infected human cells and data from ongoing clinical trials. While this study, by no means recommends specific drugs, it demonstrates a powerful deep learning methodology to prioritize existing drugs for further investigation, which holds the potential of accelerating therapeutic development for COVID-19.", "qid": 46, "docid": "j51zyodw", "rank": 87, "score": 6.155799865722656}, {"content": "Title: Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multiple-day and high-dose chemotherapy in patients with non-Hodgkin's lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study. Content: Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT3-RAs) and neurokinin 1 receptor antagonists (NK1-RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.", "qid": 46, "docid": "fdtdrpfp", "rank": 88, "score": 6.112599849700928}, {"content": "Title: Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multiple-day and high-dose chemotherapy in patients with non-Hodgkin's lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study Content: Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT3-RAs) and neurokinin 1 receptor antagonists (NK1-RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.", "qid": 46, "docid": "lw0sm5qu", "rank": 89, "score": 6.112598896026611}, {"content": "Title: COVID-19 \u2013 What does a paediatrician need to know? Content: COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.", "qid": 46, "docid": "828ubhzi", "rank": 90, "score": 6.082699775695801}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 46, "docid": "abj9b0x0", "rank": 91, "score": 6.079699993133545}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention. Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 46, "docid": "zbkgabl2", "rank": 92, "score": 6.0796990394592285}, {"content": "Title: QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review Content: Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.", "qid": 46, "docid": "e1otbzt3", "rank": 93, "score": 6.078199863433838}, {"content": "Title: QT prolongation, torsades de pointes and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review Content: Chloroquine and hydroxychloroquine are now being widely used as treatments for COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk of torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched in MEDLINE and Embase, as well as grey literature up to April 17, 2020, on the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This resulted in 390 unique records, of which fourteen were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in two COVID-19 patients out of a group of 28 treated with high-dose chloroquine. A limitation of these results is unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT interval prolongation and potentially increase the risk of arrhythmia. Daily ECG monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.", "qid": 46, "docid": "sm0112e3", "rank": 94, "score": 6.0781989097595215}, {"content": "Title: Hydrocortisone and bronchopulmonary dysplasia: variables associated with response in premature infants Content: OBJECTIVE: The primary objective was to evaluate hydrocortisone\u2019s efficacy for decreasing respiratory support in premature infants with developing bronchopulmonary dysplasia (BPD). Secondary objectives included assessment of the impact of intrauterine growth restriction (IUGR), maternal history of chorioamnionitis, side effects and route of administration associated with hydrocortisone\u2019s efficacy. Dexamethasone as second-line treatment to decrease respiratory support was reviewed. METHODS: Retrospective chart review of preterm infants requiring respiratory support receiving hydrocortisone. RESULTS: A total of 48 patients were included. Successful extubation was achieved in 50% of intubated patients after hydrocortisone treatment with no major complications. In our small study, history of maternal chorioamnionitis, IUGR or route of administration did not affect the response. Rescue dexamethasone after hydrocortisone therapy was ineffective in the ten patients who failed extubation following hydrocortisone. CONCLUSION: Hydrocortisone is effective in decreasing respiratory support in patients with developing BPD without major complications. Randomized studies are warranted to confirm our findings.", "qid": 46, "docid": "833h42d5", "rank": 95, "score": 6.054800033569336}, {"content": "Title: The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children. Content: BACKGROUND The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. OBJECTIVE The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. PATIENTS AND METHODS This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. RESULTS A total of 62 children (11.5\u00b12.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52\u00b10.52 to 6.74\u00b10.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. CONCLUSIONS This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.", "qid": 46, "docid": "32ozud9i", "rank": 96, "score": 6.030600070953369}, {"content": "Title: Comparison of the release profile and pharmacokinetics of intact and fragmented dexamethasone intravitreal implants in rabbit eyes. Content: PURPOSE Dexamethasone intravitreal implant (DEX implant, Ozurdex(\u00ae); Allergan, Inc.) is used to treat noninfectious posterior uveitis and macular edema associated with retinal vein occlusion and diabetic retinopathy. Two recently published reports of DEX implant fragmentation shortly after injection have raised concerns about the potential for faster implant dissolution and elevated ocular dexamethasone concentrations. This study compared the in vivo release profile and pharmacokinetic behavior of intact and fragmented DEX implants. METHODS DEX implant was surgically implanted as a single unit or fragmented into 3 pieces in the posterior segment of opposing eyes of 36 New Zealand white rabbits. The release of dexamethasone over time from 1-piece and 3-piece fragmented implants dissolved in solution in vitro was compared with that from the 1-piece and 3-piece fragmented implants placed in the rabbit eyes. In addition, dexamethasone concentrations in the vitreous and aqueous humors of each eye were measured at 3 h and days 1, 7, 14, 21, and 28. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used for assays. RESULTS Dexamethasone release from the 1-piece and 3-piece DEX implants in vivo was not different and was consistent with the in vitro release pattern. Moreover, the concentration profile of dexamethasone in the vitreous and aqueous humors was similar for the 1-piece and 3-piece DEX implants at each time point measured. CONCLUSIONS DEX implant fragmentation neither accelerated its dissolution nor increased the dexamethasone concentration delivered at a given time. Accordingly, DEX implant fragmentation is unlikely to have clinically significant effects in patients.", "qid": 46, "docid": "291kyeo5", "rank": 97, "score": 6.030099868774414}, {"content": "Title: Considerations for Obstetric Care during the COVID-19 Pandemic Content: The novel coronavirus disease 2019 (COVID-19) is a growing pandemic that is impacting daily life across the globe. Though disease is often mild, in high-risk populations, severe disease often leads to intubation, intensive care admission (ICU) admission, and in many cases death. The implications for pregnancy remain largely unknown. Early data suggest that COVID-19 may not pose increased risk in the pregnant population. Vertical transmission has not been confirmed. Because no treatment, no vaccine and no herd immunity exist, social distancing is the best mechanism available to protect patients and health care workers from infection. This review will discuss what is known about the virus as it relates to pregnancy and then consider management considerations based on these data. KEY POINTS: \u00b7 COVID-19 severity in pregnancy is unclear.. \u00b7 Social distancing is the best protective mechanism.. \u00b7 No clear evidence of vertical transmission exists.. \u00b7 Mother/baby separation avoids transmission..", "qid": 46, "docid": "djzh602y", "rank": 98, "score": 5.997099876403809}, {"content": "Title: Considerations for Obstetric Care during the COVID-19 Pandemic Content: The novel coronavirus disease 2019 (COVID-19) is a growing pandemic that is impacting daily life across the globe. Though disease is often mild, in high-risk populations, severe disease often leads to intubation, intensive care admission (ICU) admission, and in many cases death. The implications for pregnancy remain largely unknown. Early data suggest that COVID-19 may not pose increased risk in the pregnant population. Vertical transmission has not been confirmed. Because no treatment, no vaccine and no herd immunity exist, social distancing is the best mechanism available to protect patients and health care workers from infection. This review will discuss what is known about the virus as it relates to pregnancy and then consider management considerations based on these data. Key Points: COVID-19 severity in pregnancy is unclear. Social distancing is the best protective mechanism. No clear evidence of vertical transmission exists. Mother/baby separation avoids transmission.", "qid": 46, "docid": "kcc3p3ow", "rank": 99, "score": 5.997098922729492}, {"content": "Title: Dexamethasone and postoperative hyperglycemia in diabetics undergoing elective hip or knee arthroplasty: a case control study in 238 patients. Content: Background Dexamethasone has been routinely used in the pre-operative setting to enhance analgesia and decrease the incidence of nausea and vomiting in patients undergoing primary arthroplasty. However, dexamethasone has the potential to increase blood glucose levels postoperatively, which is a known risk factor for complications after total joint arthroplasty. The aim of this study was to analyze the effect of dexamethasone administration on post-operative blood glucose levels in diabetic patients after primary hip and knee arthroplasty. Methods This study was a retrospective review of 238 diabetic patients who underwent primary hip and knee arthroplasty between May 1, 2014 and September 30, 2016 at a single urban academic medical center. A total of 77 patients (32.4%) received dexamethasone and 161 (67.7%) did not. Oral hyperglycemic agents were held during the inpatient stay and blood glucose was controlled either with sliding scale insulin or home insulin regimens were continued. All analyses were adjusted for age, BMI, gender, type of diabetes, pre-operative diabetic medication, type of surgical procedure, and pre-operative HgbA1c level. The primary outcome was post-operative hyperglycemia within 72 h of surgery defined as any blood glucose level greater than or equal to 200 mg/dL. Results Post-operative hyperglycemia was observed in 17.1 and 20.6% of the measurements during the first 24 and 72 h respectively. After controlling for confounding variables, patients who received dexamethasone had 4.07 (95% CI: 2.46, 6.72) and 3.08 (95% CI: 2.34, 4.04) higher odds of post-operative hyperglycemia in the first 24 and 72 h respectively. Conclusions Dexamethasone administration in diabetic patients undergoing primary arthroplasty increases post-operative hyperglycemia during the first 24 and 72 h. While our data did not investigate causation, dexamethasone use in this patient population should be thoughtfully considered, as post-operative hyperglycemia is a known risk factor for complications.", "qid": 46, "docid": "rouf3dng", "rank": 100, "score": 5.968200206756592}]}
{"query": "what are the health outcomes for children who contract COVID-19?", "hits": [{"content": "Title: Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population Content: Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social shielding (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Childrens Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institutions Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings: Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist childrens hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9-14] years vs median 1 [0.1-5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation: COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing COVID-19 vulnerable medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.", "qid": 47, "docid": "15zj660u", "rank": 1, "score": 10.515700340270996}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 47, "docid": "gnaubzah", "rank": 2, "score": 9.697099685668945}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 47, "docid": "hlhhvmtu", "rank": 3, "score": 9.697098731994629}, {"content": "Title: COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review Content: Background. The prevalence of symptomatic COVID-19 in children remains low to date. In just a few months, COVID-19 has affected millions of people worldwide, and as of the date of this publication, the pandemic continues. Based on the current available evidence, children do not appear to be at higher risk of contracting COVID-19 than adults. However, children with neurological and neuromuscular conditions are vulnerable to the respiratory complications of other viral infections. Objectives. To assess whether children with brain-based developmental disabilities were more likely to develop COVID-19 and have complications or poorer outcomes following infection. Methods. We conducted a two-week rapid review on studies with primary data regarding children aged between zero and 18 years old with brain-based developmental disabilities, or who were at risk of developing such disabilities, with confirmed or suspected COVID-19. We performed our literature searches on April 18, 2020. Results. Our search strategy identified 538 individual records, of which four were included in our review. Of the 50 COVID-19 pediatric patients reported in the included studies, a total of seven children were at risk of developing brain-based disabilities. Symptoms ranged in severity. However, generally, patients were discharged or saw improvements in their symptoms by the end of the study period. No deaths were reported. Discussion. Our study highlights a knowledge gap regarding the impact of COVID-19 in children with brain-based developmental disabilities.", "qid": 47, "docid": "wjbh1z8y", "rank": 4, "score": 9.413200378417969}, {"content": "Title: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Content: Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 47, "docid": "ev9p2apu", "rank": 5, "score": 9.200300216674805}, {"content": "Title: Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not? Content: Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic", "qid": 47, "docid": "03vy3uaj", "rank": 6, "score": 9.190999984741211}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not Content: Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.", "qid": 47, "docid": "18q23z8l", "rank": 7, "score": 9.190999031066895}, {"content": "Title: Supporting children and families through the pandemic, and after: The case for a US child allowance Content: Abstract The COVID-19 pandemic has precipitated a contraction in economic activity that is unprecedented in both its nature and speed. In doing so, it has exposed who is protected and supported by modern welfare states, and who is not. While the US has a relatively robust set of social insurance and assistance programs for older Americans and working-age Americans who become unemployed or disabled, it lacks \u2013 in contrast to many other wealthy nations \u2013 a comparably strong universal or wide-reaching mechanism to support families with children. The US emergency relief packages enacted to date will undoubtedly mitigate the economic effects of the current crisis for many families, but because this legislation relies on the existing social policy infrastructure, its intended cash relief reinforces current inequalities and underserves families with children, with a particular impact on immigrant families and families of color. To protect all families with children through the immediate crisis and beyond, existing gaps and inequities in the US social safety net must be addressed. The creation of a national US child allowance offers a concrete and evidence-based way in which to do so. This analysis outlines key shortcomings in the existing system of US public support for families with children, the ways in which these shortcomings have been exacerbated in the COVID-19 economic response package to date, and how a national child allowance can provide the immediate relief families need during the pandemic and the unfolding economic downturn, as well as lay the foundation for positive health and development for all children in the years to follow.", "qid": 47, "docid": "a6myolc2", "rank": 8, "score": 9.010700225830078}, {"content": "Title: Pausing the Fight Against Malaria to Combat the COVID-19 Pandemic in Africa: Is the Future of Malaria Bleak? Content: Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In 2019, a Phase IV Expanded Programme on Immunization (EPI)-linked malaria vaccine implementation was underway. However, in December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many clinical, epidemiological, and biological parallels to malaria, was reported in Wuhan, China. COVID-19 is spreading rapidly, and, as of the 3rd of June, 2020, more than 382,507 persons had died from COVID-19. Children under 5 years who suffer high malaria-attributable mortalities are largely asymptomatic for COVID-19. Considering that the malaria burden is highest in low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hampered. Access to healthcare has generally been limited, while malaria interventions, such as seasonal malaria chemotherapy and distribution of insecticide-treated bed nets, have been suspended due to lockdowns. Likewise, the repurposing of antimalarials for treatment of COVID-19 shared symptoms and the shift in focus from the production of malaria rapid diagnostic tests (RDTs) to COVID-19 RDTs is a cause for concern in malaria-endemic regions. Children are less affected by the COVID-19 pandemic compared to the elderly. However, due to the fears of contracting SARS-CoV-2, the elderly who are worst affected by COVID-19 may not take children for malaria medication, resulting in high malaria-related mortalities among children. COVID-19 has disproportionately affected developed countries, threatening their donation capacity. These are likely to thwart malaria control efforts in low-income regions. Here, we present perspectives on the collateral impact of COVID-19 on malaria, especially in Africa.", "qid": 47, "docid": "i2338h5r", "rank": 9, "score": 8.933899879455566}, {"content": "Title: Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes. Content: BACKGROUND Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.", "qid": 47, "docid": "2qnto8gw", "rank": 10, "score": 8.88659954071045}, {"content": "Title: COVID-19 and myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimising risk of contracting coronavirus disease 2019 (COVID-19) and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post-pandemic environment, the treatment delivered to patients could be more cost-effective and better tailored than before. Healthcare delivery post-COVID-19 will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 47, "docid": "sexx9196", "rank": 11, "score": 8.729599952697754}, {"content": "Title: The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women Content: BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organization.", "qid": 47, "docid": "6ipv3lf6", "rank": 12, "score": 8.702899932861328}, {"content": "Title: The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women Content: BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organisation.", "qid": 47, "docid": "m66npv9k", "rank": 13, "score": 8.702898979187012}, {"content": "Title: Covid\u201019 and Myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimizing risk of contracting COVID\u201019 and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post\u2010pandemic environment, the treatment delivered to patients could be more cost effective and better tailored than before. Healthcare delivery post\u2010COVID will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 47, "docid": "njg0ln33", "rank": 14, "score": 8.695799827575684}, {"content": "Title: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review Content: BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "qid": 47, "docid": "998lscmk", "rank": 15, "score": 8.667900085449219}, {"content": "Title: Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic. Content: COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of \"social distancing,\" reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered \"elective,\" balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.", "qid": 47, "docid": "jkmihpt5", "rank": 16, "score": 8.594200134277344}, {"content": "Title: Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic Content: COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of \"social distancing,\" reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered \"elective,\" balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.", "qid": 47, "docid": "uiy18hx9", "rank": 17, "score": 8.594199180603027}, {"content": "Title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Content: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: \u00e2\u0080\u00a2 There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: \u00e2\u0080\u00a2 Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. \u00e2\u0080\u00a2 However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.", "qid": 47, "docid": "u7arfoym", "rank": 18, "score": 8.545599937438965}, {"content": "Title: Case-Initiated COVID-19 Contact Tracing Using Anonymous Notifications Content: We discuss the concept of a participatory digital contact notification approach to assist tracing of contacts who are exposed to confirmed cases of coronavirus disease (COVID-19); the approach is simple and affordable for countries with limited access to health care resources and advanced technology. The proposed tool serves as a supplemental contract tracing approach to counteract the shortage of health care staff while providing privacy protection for both cases and contacts. This tool can be deployed on the internet or as a plugin for a smartphone app. Confirmed cases with COVID-19 can use this tool to provide contact information (either email addresses or mobile phone numbers) of close contacts. The system will then automatically send a message to the contacts informing them of their contact status, what this status means, the actions that should follow (eg, self-quarantine, respiratory hygiene/cough etiquette), and advice for receiving early care if they develop symptoms. The name of the sender of the notification message by email or mobile phone can be anonymous or not. The message received by the contact contains no disease information but contains a security code for the contact to log on the platform to retrieve the information.", "qid": 47, "docid": "qmp2h3h2", "rank": 19, "score": 8.539600372314453}, {"content": "Title: What Solid Organ Transplant Healthcare Providers should know about Renin\u2010Angiotensin\u2010Aldosterone System Inhibitors and COVID\u201019 Content: The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID\u201019) are still emerging. Kidney transplant recipients are commonly prescribed renin\u2010angiotensin\u2010aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin\u2010converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of Renin\u2010Angiotensin\u2010Aldosterone System (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS\u2010CoV\u20102 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID\u201019 pandemic. At present there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID\u201019 pandemic.", "qid": 47, "docid": "90d21ck7", "rank": 20, "score": 8.52810001373291}, {"content": "Title: What solid organ transplant healthcare providers should know about renin-angiotensin-aldosterone system inhibitors and COVID-19 Content: The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID-19) are still emerging. Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic. At present, there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID-19 pandemic.", "qid": 47, "docid": "j9vpgw4v", "rank": 21, "score": 8.528099060058594}, {"content": "Title: Anxiety regarding contracting COVID-19 related to interoceptive anxiety sensations: The moderating role of disgust propensity and sensitivity Content: The COVID-19 public health crisis has led to extensive recommendations by officials to contain its spread. Anxiety regarding contracting the virus is prominent in the public. Specific routes to anxiety over disease contraction are under studied. It is expected that a contributory feature of fear of contracting COVID-19 involve disgust propensity and sensitivity, emotional reactions that are part of a broader behavioral immune system (BIS). A total of N = 908 Chinese adults (mean age = 40.37 years, SD = 9.27; n = 752 female) participated in a survey distributed between February 24 and March 15, 2020. Participants completed measures of anxiety sensitivity, disgust propensity and sensitivity, and fear of contracting COVID-19. Results support a moderating relationship between both disgust propensity and sensitivity in the relationship between physical concerns associated with anxiety sensitivity and fear of contracting COVID-19. These results lend support for individual variation in the activation of the BIS. Recommendations for public education to target individuals who may experience mental health consequences from pandemics are provided.", "qid": 47, "docid": "lm18i64j", "rank": 22, "score": 8.522000312805176}, {"content": "Title: Anxiety Regarding Contracting COVID-19 Related to Interoceptive Anxiety Sensations: The Moderating Role of Disgust Propensity and Sensitivity Content: Abstract The COVID-19 public health crisis has led to extensive recommendations by officials to contain its spread. Anxiety regarding contracting the virus is prominent in the public. Specific routes to anxiety over disease contraction are under studied. It is expected that a contributory feature of fear of contracting COVID-19 involve disgust propensity and sensitivity, emotional reactions that are part of a broader behavioral immune system (BIS). A total of N = 908 Chinese adults (mean age = 40.37 years, SD = 9.27; n = 752 female) participated in a survey distributed between February 24 and March 15, 2020. Participants completed measures of anxiety sensitivity, disgust propensity and sensitivity, and fear of contracting COVID-19. Results support a moderating relationship between both disgust propensity and sensitivity in the relationship between physical concerns associated with anxiety sensitivity and fear of contracting COVID-19. These results lend support for individual variation in the activation of the BIS. Recommendations for public education to target individuals who may experience mental health consequences from pandemics are provided.", "qid": 47, "docid": "ow9mn18o", "rank": 23, "score": 8.52199935913086}, {"content": "Title: Preference Refinement After a Budget Contraction Content: How does coping with a resource loss of time, space, or money change a consumer? In the current work, we argue that resource losses that give rise to budget contractions require a coping strategy that not only influences choice in the moment but also changes underlying consumer preferences. We show that the preference restructuring that occurs when coping with a budget loss also leads to stabilization of preferences. Specifically, a consumer who allocates a budget to a set of items prior to a budget contraction and allocates that same budget post-contraction when the budget is fully restored will allocate the restored budget to fewer options in the set. Coping with the contraction helps consumers prioritize what matters to them, leading to refinement of preference. This within-consumer preference refinement effect exists for budgets of time, space, and money. We identify boundary conditions (i.e., significant budget contractions and self-determined contraction allocations are necessary for prioritization to occur) and rule out non-prioritization explanations (e.g., anchoring and under-adjusting). These findings suggest that marketers should focus on capturing consumers who are dealing with budget contractions as this is one of the moments where individuals revisit and rediscover what matters most to them.", "qid": 47, "docid": "cyn4ssih", "rank": 24, "score": 8.508899688720703}, {"content": "Title: Perceived vulnerability to COVID-19 infection from event attendance: Results from Louisiana, USA, two weeks preceding the national emergency declaration Content: In response to the mounting threat of COVID-19, we added questions to an ongoing food preference study held at Louisiana State University from March 3-12 of 2020. We asked 356 participants: (1) In your opinion, how likely is it that the spread of COVID-19 (the coronavirus) will cause a public health crisis in the United States? (2) How concerned are you that you will contract COVID-19 by attending events on campus? Participants' estimates of an impending national health crisis increased significantly during the study's second week (March 9-12) while concern about personally contracting COVID-19 from attending campus events increased only marginally during the study's final days. We find those expressing a higher likelihood of an impending national crisis were more concerned about contracting COVID-19 by attending campus events, suggesting a possible transmission from perceptions of national-level events to perceived personal vulnerability via local exposure. However, about 30% of participants perceived that COVID-19 would likely cause a public health crisis yet did not express concern about contracting COVID-19 from event attendance. These participants were significantly more likely to be younger students who agreed to participate in response to recruitment using same-day flyer distribution. Women expressed a higher likelihood of an emerging national health crisis, although they were not more concerned than men that attending campus events would result in virus contraction. Other groups (e.g., white, students younger than 25, highest income group) displayed similar concern about a national-level crisis, yet were significantly less concerned about contracting COVID-19 from attending campus events than others. Also, participants randomly assigned to information emphasizing the national impacts of food waste expressed significantly greater concern of contracting COVID-19 by attending campus events. These results provide some initial insight about how people perceived national and personal risks in the early stages of the COVID-19 crisis in Louisiana.", "qid": 47, "docid": "hng8ivz2", "rank": 25, "score": 8.451700210571289}, {"content": "Title: An International Review of Tobacco Use and the COVID-19 Pandemic: Examining Hospitalization, Asymptomatic Cases, and Severity Content: Background and objectives: Since the World Health Organization (WHO) declared a public health emergency of imminent concern in March 2020, the novel coronavirus (SARS-CoV-2) and its related disease (COVID-19) has become a topic of much-needed research. This study primarily focused on what effect smoking had on hospitalization; however, asymptomaticity and severity were discussed. Data: Data was collected through searches on databases including PubMed and Google Scholar. Eligibility criteria included being RT-PCR verified and including smoking data. Discussion: This study found that smokers were significantly underrepresented in COVID-19 hospitalization on a purely epidemiological level in some areas, including China and Manhattan, but not others: Seattle, Greater New York City Area, and Italy. Furthermore, smokers were equally represented in asymptomatic populations, but smokers will likely experience a more severe manifestation of the disease if they are symptomatic. Further inquiry into possible mechanisms by which the observed epidemiological effect is necessary, as it has implications for recommendations on loosening restrictions on social distancing measures. Conclusions and Recommendations: This study recommends that smokers consider themselves to be at higher risk for COVID-19, as they may experience a more severe manifestation of the disease. Health care providers and policymakers should consider smokers at higher risk as well, as there is evidence to claim that smokers may contract a more severe form of COVID-19.", "qid": 47, "docid": "k9k1bwg6", "rank": 26, "score": 8.444700241088867}, {"content": "Title: Evaluation and mechanism for outcomes exploration of providing public health care in contract service in Rural China: a multiple-case study with complex adaptive systems design Content: BACKGROUND: The Chinese government has increased the funding for public health in 2009 and experimentally applied a contract service policy (could be seen as a counterpart to family medicine) in 15 counties to promote public health services in the rural areas in 2013. The contract service aimed to convert village doctors, who had privately practiced for decades, into general practitioners under the government management, and better control the rampant chronic diseases. This study made a rare attempt to assess the effectiveness of public health services delivered under the contract service policy, explore the influencing mechanism and draw the implications for the policy extension in the future. METHODS: Three pilot counties and a non-pilot one with heterogeneity in economic and health development from east to west of China were selected by a purposive sampling method. The case study methods by document collection, non-participant observation and interviews (including key informant interview and focus group interview) with 84 health providers and 20 demanders in multiple level were applied in this study. A thematic approach was used to compare diverse outcomes and analyze mechanism in the complex adaptive systems framework. RESULTS: Without sufficient incentives, the public health services were not conducted effectively, regardless of the implementation of the contract policy. To appropriately increase the funding for public health by local finance and properly allocate subsidy to village doctors was one of the most effective approaches to stimulate health providers and demanders\u2019 positivity and promote the policy implementation. County health bureaus acted as the most crucial agents among the complex public health systems. Their mental models influenced by the compound and various environments around them led to the diverse outcomes. If they could provide extra incentives and make the contexts of the systems ripe enough for change, the health providers and demanders would be receptive to the transition of the policy. CONCLUSIONS: The innovative fund raising measures could be taken by relatively developed counties of China to conduct public health services. Policymakers could take systems thinking as a useful tool to design plans and predict the unintended outcomes during the process of public health reforms.", "qid": 47, "docid": "29aqx87q", "rank": 27, "score": 8.382100105285645}, {"content": "Title: Electrocardiographic Findings in Coronavirus Disease-19: Insights on Mortality and Underlying Myocardial Processes Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. METHODS AND RESULTS: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. THERE WERE: 756 patients who presented to a large New York City teaching hospital with COVID-19 who underwent an ECG. The mean age was 63.3 \u00b1 16 years, 37% were women, 61% of patients were nonwhite, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.23-5.36, P\u00e2\u0080\u00af=\u00e2\u0080\u00af.01), a right bundle branch block or intraventricular block (OR 2.61, 95% CI 1.32-5.18, P\u00e2\u0080\u00af=\u00e2\u0080\u00af.002), ischemic T-wave inversion (OR 3.49, 95% CI 1.56-7.80, P\u00e2\u0080\u00af=\u00e2\u0080\u00af.002), and nonspecific repolarization (OR 2.31, 95% CI 1.27-4.21, P\u00e2\u0080\u00af=\u00e2\u0080\u00af.006) increased the odds of death. ST elevation was rare (n\u00e2\u0080\u00af=\u00e2\u0080\u00af5 [0.7%]). CONCLUSIONS: We found that patients with ECG findings of both left-sided heart disease (atrial premature contractions, intraventricular block, repolarization abnormalities) and right-sided disease (right bundle branch block) have higher odds of death. ST elevation at presentation was rare.", "qid": 47, "docid": "0848vz0q", "rank": 28, "score": 8.378299713134766}, {"content": "Title: Smoking Is Associated With COVID-19 Progression: A Meta-analysis Content: INTRODUCTION: Smoking depresses pulmonary immune function and is a risk factor contracting other infectious diseases and more serious outcomes among people who become infected. This paper presents a meta-analysis of the association between smoking and progression of the infectious disease COVID-19. METHODS: PubMed was searched on April 28, 2020, with search terms \u201csmoking\u201d, \u201csmoker*\u201d, \u201ccharacteristics\u201d, \u201crisk factors\u201d, \u201coutcomes\u201d, and \u201cCOVID-19\u201d, \u201cCOVID\u201d, \u201ccoronavirus\u201d, \u201csar cov-2\u201d, \u201csar cov 2\u201d. Studies reporting smoking behavior of COVID-19 patients and progression of disease were selected for the final analysis. The study outcome was progression of COVID-19 among people who already had the disease. A random effects meta-analysis was applied. RESULTS: We identified 19 peer-reviewed papers with a total of 11,590 COVID-19 patients, 2,133 (18.4%) with severe disease and 731 (6.3%) with a history of smoking. A total of 218 patients with a history of smoking (29.8%) experienced disease progression, compared with 17.6% of non-smoking patients. The meta-analysis showed a significant association between smoking and progression of COVID-19 (OR 1.91, 95% confidence interval [CI] 1.42-2.59, p = 0.001). Limitations in the 19 papers suggest that the actual risk of smoking may be higher. CONCLUSIONS: Smoking is a risk factor for progression of COVID-19, with smokers having higher odds of COVID-19 progression than never smokers. IMPLICATIONS: Physicians and public health professionals should collect data on smoking as part of clinical management and add smoking cessation to the list of practices to blunt the COVID-19 pandemic.", "qid": 47, "docid": "2dt758qj", "rank": 29, "score": 8.37279987335205}, {"content": "Title: COVID-19: Four Paediatric Cases in Malaysia Content: OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.", "qid": 47, "docid": "h4kmrxeu", "rank": 30, "score": 8.350700378417969}, {"content": "Title: COVID-19: Four Paediatric Cases in Malaysia Content: Abstract Objective This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia Background COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. Cases In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. Discussion There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.", "qid": 47, "docid": "xubsqetp", "rank": 31, "score": 8.350699424743652}, {"content": "Title: First Case of an Infant with COVID-19 in the Middle East Content: The novel coronavirus (COVID-19) has been declared a worldwide pandemic. It was initially thought to spare children and adolescents as significantly smaller number of cases have been reported in the pediatric population in comparison to adults. Here, we report the case of a 16-month-old female infant from Lebanon who presented with fever and severe diarrhea and tested positive for COVID-19. Her symptoms started six days prior to presentation with no cough, rhinorrhea, or other respiratory manifestations reported. Chest radiography showed lobar consolidation and bronchial infiltrates. Blood culture was positive for Streptococcus pneumoniae. Stool and urine cultures were negative. She was treated with ceftriaxone and metronidazole. Her RT-PCR test was negative after five days of treatment, suggesting that children can clear the virus faster than adults. The patient likely contracted the virus from her parents, who because of the fear of social stigma hide recent history of respiratory illness. These findings serve as a practical reference for the clinical diagnosis and medical treatment of children with COVID-19.", "qid": 47, "docid": "5sgfx7oq", "rank": 32, "score": 8.348099708557129}, {"content": "Title: COVID-19 related concerns of people with long-term respiratory conditions: A qualitative study Content: BACKGROUND The COVID-19 pandemic is having profound psychological impacts on populations globally, with increasing levels of stress, anxiety, and depression being reported, especially in people with pre-existing medical conditions who appear to be particularly vulnerable. There are limited data on the specific concerns people have about COVID-19 and what these are based on. METHODS The aim of this study was to identify and explore the concerns of people with long-term respiratory conditions in the UK regarding the impact of the COVID-19 pandemic and how these concerns were affecting them. We conducted a thematic analysis of free text responses to the question 'What are your main concerns about getting coronavirus?', which was included in the British Lung Foundation/Asthma UK (BLF-AUK) partnership COVID-19 survey, conducted between the 1st and 8th of April. This was during the 3rd week of the UK's initial social distancing measures. RESULTS 7,039 responses were analysed, with respondents from a wide range of ages, gender, and all UK nations. Respondents reported having asthma (85%), COPD (9%), bronchiectasis (4%), interstitial lung disease (2%), or 'other' lung diseases (e.g. lung cancer) (1%). Four main themes were identified: 1) vulnerability to COVID-19; 2) anticipated experience of contracting COVID-19; 3) wide-reaching uncertainty; and 4) inadequate national response. CONCLUSIONS The COVID-19 pandemic is having profound psychological impacts. The concerns we identified largely reflect objective, as well as subjective, aspects of the current situation. Hence, key approaches to reducing these concerns require changes to the reality of their situation, and are likely to include i) helping people optimise their health, limit risk of infection, and access necessities; ii) minimising the negative experience of disease where possible, iii) providing up-to-date, accurate and consistent information, iv) improving the government and healthcare response.", "qid": 47, "docid": "pwoe3p1p", "rank": 33, "score": 8.297599792480469}, {"content": "Title: Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID-19 pandemic Content: BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID-19. The patients who received treatment and got affected with COVID-19 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID-19, is an advisable strategy based on this model.", "qid": 47, "docid": "54d3p49g", "rank": 34, "score": 8.25570011138916}, {"content": "Title: Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID\u201019 pandemic Content: BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID\u201019. The patients who received treatment and got affected with COVID\u201019 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID\u201019, is an advisable strategy based on this model.", "qid": 47, "docid": "jqkp8u5v", "rank": 35, "score": 8.255699157714844}, {"content": "Title: Disability-inclusive COVID-19 response: What it is, why it is important and what we can learn from the United Kingdom\u2019s response Content: All too often, disabled people are left behind in emergencies, and this is a risk in the ongoing COVID-19 pandemic. This is an important issue, as globally there are approximately one billion people with disabilities. This number includes one in three people aged over 60, who are the group at greatest risk from COVID-19. The COVID-19 pandemic in the UK has highlighted additional difficulties that disabled people may face. Complying with preventative measures, like social distancing, can be challenging, particular for people who rely on carers. Disabled people may also be at greater risk of morbidity and mortality if they contract the virus, yet in danger of being de-prioritised for care. Many people with disabilities have ongoing healthcare needs, and these need to still be supported during the pandemic. Furthermore, people may become newly disabled as a result of the pandemic, and therefore require appropriate care. Good practice examples have emerged for meeting these challenges, such as guidance for healthcare professionals on treating people with dementia, but these need to be scaled up further and adapted for other settings. In conclusion, it is clear that a disability-inclusive COVID-19 response is needed, both in the UK and as the pandemic unfolds globally. This response will require inclusion of disability measures within data collection, consulting with disabled people, and tailoring responses to be appropriate for this group.", "qid": 47, "docid": "t38qv5py", "rank": 36, "score": 8.247099876403809}, {"content": "Title: In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries Content: BACKGROUND: A variety of in-service emergency care training courses are currently being promoted as a strategy to improve the quality of care provided to seriously ill newborns and children in low-income countries. Most courses have been developed in high-income countries. However, whether these courses improve the ability of health professionals to provide appropriate care in low-income countries remains unclear. This is the first update of the original review. OBJECTIVES: To assess the effects of in-service emergency care training on health professionals' treatment of seriously ill newborns and children in low-income countries. SEARCH METHODS: For this update, we searched the Cochrane Database of Systematic Reviews, part of The Cochrane Library (http://www.cochranelibrary.com); MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (http://www.cochranelibrary.com) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge/Science and eight other databases. We performed database searches in February 2015. We also searched clinical trial registries, websites of relevant organisations and reference lists of related reviews. We applied no date, language or publication status restrictions when conducting the searches. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before and after studies and interrupted-time-series studies that compared the effects of in-service emergency care training versus usual care were eligible for inclusion. We included only hospital-based studies and excluded community-based studies. Two review authors independently screened and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables. MAIN RESULTS: We identified no new studies in this update. Two randomised trials (which were included in the original review) met the review eligibility criteria. In the first trial, newborn resuscitation training compared with usual care improved provider performance of appropriate resuscitation (trained 66% vs usual care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty evidence). Findings from the second trial suggest that essential newborn care training compared with usual care probably slightly improves delivery room newborn care practices (assessment of breathing, preparedness for resuscitation) (moderate certainty evidence). AUTHORS' CONCLUSIONS: In-service neonatal emergency care courses probably improve health professionals' treatment of seriously ill babies in the short term. Further multi-centre randomised trials evaluating the effects of in-service emergency care training on long-term outcomes (health professional practice and patient outcomes) are needed. PLAIN LANGUAGE SUMMARY: In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries WHAT QUESTION WAS THE REVIEW ASKING? This is the first update of the original Cochrane review, whose objective was to find out whether additional emergency care training programmes can improve the ability of health workers in poor countries to care for seriously ill newborns and children admitted to hospitals. Researchers at The Cochrane Collaboration searched for all studies that could answer this question and found two relevant studies. WHAT ARE THE KEY MESSAGES? The review authors suggest that giving health professionals in poor countries additional training in emergency care probably improves their ability to care for seriously ill newborns. We need additional high-quality studies, including studies in which health professionals are trained to care for seriously ill older children. BACKGROUND: TRAINING HEALTH PROFESSIONALS TO CARE FOR SERIOUSLY ILL BABIES AND CHILDREN: In poor countries, many babies and children with serious illnesses die even though they have been cared for in hospitals. One reason for this may be that health workers in these countries often are not properly trained to offer the care that these children need. In poor countries, children often become seriously ill because of conditions such as pneumonia, meningitis and diarrhoea, and may need emergency care. For newborn babies, the most common reason for emergency care is too little oxygen to the baby during birth. If this goes on for too long, the person delivering the baby has to help the baby breathe, and sometimes has to get the baby's heart rate back to normal. This is called neonatal resuscitation. Neonatal resuscitation is a skilled task, and the health worker needs proper training. As babies need to be resuscitated quickly, the health worker needs to know how to prepare for this before the baby is born. For instance, he or she needs to know how to prepare the room and proper equipment. Health workers in poor countries often do not have these skills, and these babies are likely to die. Babies can also be harmed if the health worker does not resuscitate the baby correctly. Several training programmes have been developed to teach health workers how to give emergency care to seriously ill babies and children. But most of these have been developed and tested in wealthy countries, and we don't know whether they would work in poor countries. WHAT HAPPENS WHEN HEALTH PROFESSIONALS IN POOR COUNTRIES ARE GIVEN EXTRA TRAINING? The review authors found two relevant studies. These studies compared the practices of health professionals who had been given extra training in the care of newborns with the practices of health professionals who did not receive extra training. In the first study, nurses at a maternity hospital in Kenya completed a one-day training course on how to resuscitate newborn babies. This course was adapted from the UK Resuscitation Council, and it included lectures and practical training. The study suggests that after these training courses: health professionals are probably more likely to resuscitate newborn babies correctly (moderate certainty of the evidence); and newborn babies may be less likely to die while being resuscitated (low certainty of the evidence). In the second study, doctors, nurses and midwives in five Sri Lankan hospitals were given a four-day training course on how to prepare for and provide care for newborns. This course was adapted from the World Health Organization (WHO) Training Modules on Essential Newborn Care and Breastfeeding, and included lectures, demonstrations, hands-on training and small group discussions. This study suggests that after these training courses: health professionals probably are more likely to be well prepared to resuscitate newborn babies (moderate certainty of the evidence). Unfortunately, the two studies followed up with health professionals for only two to three months after they received training. We therefore don't know if the benefits of the training courses lasted over time. The review authors found no studies that looked at the effects of training programmes on the care of older children. HOW UP-TO-DATE IS THIS REVIEW? Review authors searched for studies that had been published up to February 2015.", "qid": 47, "docid": "16b8drw2", "rank": 37, "score": 8.137999534606934}, {"content": "Title: Guidance for the Treatment and Management of COVID\u201019 Among People with Intellectual Disabilities Content: The current COVID\u201019 pandemic is a pressing world crisis and people with intellectual disabilities (IDs) are vulnerable due to disparity in healthcare provision and physical and mental health multimorbidity. While most people will develop mild symptoms upon contracting severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102), some will develop serious complications. The aim of this study is to present guidelines for the care and treatment of people with IDs during the COVID\u201019 pandemic for both community teams providing care to people with IDs and inpatient psychiatric settings. The guidelines cover specific issues associated with hospital passports, individual COVID\u201019 care plans, the important role of families and carers, capacity to make decisions, issues associated with social distancing, ceiling of care/treatment escalation plans, mental health and challenging behavior, and caring for someone suspected of contracting or who has contracted SARS\u2010CoV\u20102 within community or inpatient psychiatric settings. We have proposed that the included conditions recommended by Public Health England to categorize someone as high risk of severe illness due to COVID\u201019 should also include mental health and challenging behavior. There are specific issues associated with providing care to people with IDs and appropriate action must be taken by care providers to ensure that disparity of healthcare is addressed during the COVID\u201019 pandemic. We recognize that our guidance is focused upon healthcare delivery in England and invite others to augment our guidance for use in other jurisdictions.", "qid": 47, "docid": "bis2arbu", "rank": 38, "score": 8.084099769592285}, {"content": "Title: Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal Content: Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011\u20132014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.", "qid": 47, "docid": "fz30r73d", "rank": 39, "score": 8.045299530029297}, {"content": "Title: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children Content: Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for some initial updates in neuropsychology practice.", "qid": 47, "docid": "1wrwxb9b", "rank": 40, "score": 8.018699645996094}, {"content": "Title: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children. Content: Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for relevant for some initial updates in neuropsychology practice.", "qid": 47, "docid": "lbsacgr7", "rank": 41, "score": 8.018698692321777}, {"content": "Title: Novel coronavirus infection and children. Content: BACKGROUND AND AIM Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS We searched Pubmed, from January to April 2020, for the following search terms: \"COVID-19\", \"children\", \"SARS-COV2\", \"complications\", \"epidemiology\", \"clinical features\", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.", "qid": 47, "docid": "c2iibuqa", "rank": 42, "score": 7.978700160980225}, {"content": "Title: Novel coronavirus infection and children Content: BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS: We searched Pubmed, from January to April 2020, for the following search terms: \"COVID-19\", \"children\", \"SARS-COV2\", \"complications\", \"epidemiology\", \"clinical features\", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS: Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.", "qid": 47, "docid": "uvvsiltp", "rank": 43, "score": 7.978699207305908}, {"content": "Title: The Impact of COVID-19 on HIV Treatment and Research: A Call to Action Content: The impact of the COVID-19 pandemic is far reaching, with devastating effects on individuals, communities, and societies across the world. People with chronic health conditions may be at greater risk of contracting or experiencing complications from COVID-19. In addition to illness or death for those who contract the virus, the physical distancing required to flatten the curve of new cases is having a negative impact on the economy, the effects of which intersect with mental health and other existing health concerns, thus affecting marginalized communities. Given that HIV also has a disproportionate impact on marginalized communities, COVID-19 is affecting people with HIV (PWH) in unique ways and will continue to have an impact on HIV research and treatment after the COVID-19 crisis passes. Using the biopsychosocial framework to contextualize the impact of COVID-19 on PWH, the purpose of this review article is to: (1) outline the similarities and differences between the COVID-19 and HIV pandemics; (2) describe the current and future impact of COVID-19 on PWH; and (3) outline a call to action for scientists and practitioners to respond to the impact of COVID-19 on HIV prevention and treatment.", "qid": 47, "docid": "53b4lrk2", "rank": 44, "score": 7.9274001121521}, {"content": "Title: Novel Coronavirus (nCoV): a Bitter Old Enemy in a New Avatar Content: Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.", "qid": 47, "docid": "1ij25a7u", "rank": 45, "score": 7.906499862670898}, {"content": "Title: Pandemic (H1N1) 2009 risk for frontline health care workers. Content: To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84-2.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant's family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.", "qid": 47, "docid": "bri67c94", "rank": 46, "score": 7.8831000328063965}, {"content": "Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers Content: To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84\u20132.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant\u2019s family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.", "qid": 47, "docid": "ul8wjrmy", "rank": 47, "score": 7.88309907913208}, {"content": "Title: Novel coronavirus infection in children outside of Wuhan, China Content: BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.", "qid": 47, "docid": "nb8hpst0", "rank": 48, "score": 7.881400108337402}, {"content": "Title: Novel coronavirus infection in children outside of Wuhan, China Content: BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID\u201019) has spread rapidly, but information about children with COVID\u201019 is limited. METHODS: This retrospective and the single\u2010center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID\u201019 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019\u2010nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019\u2010nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground\u2010glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT\u2010PCR for 2019\u2010nCoV and were discharged. The median time from exposure to a negative RT\u2010PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.", "qid": 47, "docid": "txssq1p1", "rank": 49, "score": 7.881399154663086}, {"content": "Title: Pediatric obesity-related curricular content and training in dental schools and dental hygiene programs: systematic review and recommendations. Content: OBJECTIVES The authors conducted a systematic review to determine: a) What dental schools and dental hygiene programs are doing to promote knowledge and skills related to addressing childhood obesity and to reduce consumption of sugar-sweetened beverages (SSBs) and b) What else these schools and programs could do to better equip future oral health professionals to address childhood obesity and reduce consumption of SSBs. METHODS The authors searched PubMed, Scopus, Education Full Text (EBSCOHost), and ERIC (EBSCOHost) to identify peer-reviewed publications reporting on obesity or dietetic-related curricula in dental and dental hygiene education within the last 20 years. Three studies met inclusion and exclusion criteria. Outcomes of the identified studies were abstracted and summarized independently by two investigators. RESULTS The first study describes a 2009 survey of pediatric dentistry residents. Approximately, half had received formal training yet they lacked essential knowledge or skills for managing children who were obese. The second study describes nutrition-related coursework offered in the second year of a predoctoral dental school curriculum in Saudi Arabia, and the third study reports on the development of an \"oral health rotation\" dietetic internship in a pediatric dentistry clinic, in the context of interprofessional education (IPE). CONCLUSIONS Evidence of dental schools' and dental hygiene programs' efforts to address obesity and SSB consumption in children in their curricula is scant, while Commission on Dental Accreditation standards make sporadic mentions of diet and nutrition. Opportunities exist to leverage existing resources and innovative, experiential approaches, including IPE, to formally, and effectively address this important issue in predoctoral oral health education.", "qid": 47, "docid": "0d4scwei", "rank": 50, "score": 7.769700050354004}, {"content": "Title: SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital Content: OBJECTIVE: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children's hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children's Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the ED or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21 March 2020, until 19 April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 [76%]) or RIC (102 [24%]). There were four (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients. CONCLUSION: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.", "qid": 47, "docid": "ef1qr82d", "rank": 51, "score": 7.742099761962891}, {"content": "Title: SARS\u2010CoV\u20102 Testing and Outcomes in the First 30 Days after the First Case of COVID\u201019 at an Australian Children\u2019s Hospital Content: OBJECTIVE: International studies describing COVID\u201019 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS\u2010CoV\u20102 at a large Australian tertiary children\u2019s hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children\u2019s Hospital, Melbourne, Australia. It included all paediatric patients (aged 0\u201318 years) who presented to the Emergency Department (ED) or the Respiratory Infection Clinic (RIC) and were tested for SARS\u2010CoV\u20102. The 30\u2010day study period commenced after the first confirmed positive case was detected at the hospital on 21(st) March 2020, until 19(th) April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS\u2010CoV\u20102 testing was performed in ED (331 (76%)) or RIC (102 (24%)). There were 4 (0.9%) who had positive SARS\u2010CoV\u20102 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS\u2010CoV\u20102 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS\u2010CoV\u20102 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID\u201019 were identified in 4/4 SARS\u2010CoV\u20102 positive patients and 47/429 (11%) SARS\u2010CoV\u20102 negative patients. CONCLUSIONS: Our study identified a very low rate of SARS\u2010CoV\u20102 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS\u2010CoV\u20102 negative had comorbidities.", "qid": 47, "docid": "feyu4bgc", "rank": 52, "score": 7.742098808288574}, {"content": "Title: Risk factors for contracting watery diarrhoea in Kadoma City, Zimbabwe, 2011: a case control study Content: BACKGROUND: Kadoma City experienced an increase in watery diarrhoea from 27 cases during week beginning 5(th) September, to 107 cases during week beginning 26(th) September 2011. The weekly diarrhoea cases crossed the threshold action line during week beginning 5(th) September at the children\u2019s clinic in Rimuka Township, and the remaining four clinics reported cases crossing threshold action lines between week beginning 12(th) September and week beginning 26(th) September. Eighty-two percent of the cases were children less than 5 years old. We conducted a case controlstudy to determine risk factorsfor contracting watery diarrhoea in children less than 5 years in Kadoma City. METHODS: An unmatched 1:1 case control study was conducted in Ngezi and Rimuka townships in Kadoma City, Zimbabwe. A case was a child less than 5 years old, who developed acute watery diarrhoea between 5(th) September and 1(st) October 2011. A control was a child less than 5 years old who stayed in the same township and did not suffer from diarrhoea. A structured questionnaire was administered to caregivers of cases and controls.Laboratory water quality tests and stool test results were reviewed.Epi Info\u2122 statistical software was used to analyse data. RESULTS: A total of 109 cases and 109 controls were enrolled. Independent protective factors were: having been exclusively breastfed for six months [AOR = 0.44; 95% CI (0.24-0.82)]; using municipal water [AOR = 0.38; 95% CI (0.18-0.80)]; using aqua tablets, [AOR = 0.49; 95% CI (0.26\u20130.94)] and; storing water in closed containers, [AOR = 0.24; 95% CI (0.07\u20130.0.83). The only independent risk factor for contracting watery diarrhoea was hand washing in a single bowl, [AOR = 2.89; 95% CI (1.33\u20136.28)]. Salmonella, Shigella, Rotavirus, and Enteropathogenic Escherichia coli were isolated in the stool specimens. None of the 33 municipal water samples tested showed contamination with Escherichia coli, whilst 23 of 44 (52%) shallow well water samples and 3 of 15(20%) borehole water samples tested were positive for Escherichia coli. CONCLUSIONS: The outbreak resulted from inadequate clean water and use of contaminated water. Evidence from this study was used to guide public health response to the outbreak.", "qid": 47, "docid": "qfvm883x", "rank": 53, "score": 7.741199970245361}, {"content": "Title: Aerosol-generating otolaryngology procedures and the need for enhanced PPE during the COVID-19 pandemic: a literature review Content: BACKGROUND: Adequate personal protective equipment is needed to reduce the rate of transmission of COVID-19 to health care workers. Otolaryngology groups are recommending a higher level of personal protective equipment for aerosol-generating procedures than public health agencies. The objective of the review was to provide evidence that a.) demonstrates which otolaryngology procedures are aerosol-generating, and that b.) clarifies whether the higher level of PPE advocated by otolaryngology groups is justified. MAIN BODY: Health care workers in China who performed tracheotomy during the SARS-CoV-1 epidemic had 4.15 times greater odds of contracting the virus than controls who did not perform tracheotomy (95% CI 2.75-7.54). No other studies provide direct epidemiological evidence of increased aerosolized transmission of viruses during otolaryngology procedures. Experimental evidence has shown that electrocautery, advanced energy devices, open suctioning, and drilling can create aerosolized biological particles. The viral load of COVID-19 is highest in the upper aerodigestive tract, increasing the likelihood that aerosols generated during procedures of the upper aerodigestive tract of infected patients would carry viral material. Cough and normal breathing create aerosols which may increase the risk of transmission during outpatient procedures. A significant proportion of individuals infected with COVID-19 may not have symptoms, raising the likelihood of transmission of the disease to inadequately protected health care workers from patients who do not have probable or confirmed infection. Powered air purifying respirators, if used properly, provide a greater level of filtration than N95 masks and thus may reduce the risk of transmission. CONCLUSION: Direct and indirect evidence suggests that a large number of otolaryngology-head and neck surgery procedures are aerosol generating. Otolaryngologists are likely at high risk of contracting COVID-19 during aerosol generating procedures because they are likely exposed to high viral loads in patients infected with the virus. Based on the precautionary principle, even though the evidence is not definitive, adopting enhanced personal protective equipment protocols is reasonable based on the evidence. Further research is needed to clarify the risk associated with performing various procedures during the COVID-19 pandemic, and the degree to which various personal protective equipment reduces the risk.", "qid": 47, "docid": "f6tr0ntz", "rank": 54, "score": 7.691100120544434}, {"content": "Title: Aerosol-generating otolaryngology procedures and the need for enhanced PPE during the COVID-19 pandemic: a literature review Content: BACKGROUND: Adequate personal protective equipment is needed to reduce the rate of transmission of COVID-19 to health care workers. Otolaryngology groups are recommending a higher level of personal protective equipment for aerosol-generating procedures than public health agencies. The objective of the review was to provide evidence that a.) demonstrates which otolaryngology procedures are aerosol-generating, and that b.) clarifies whether the higher level of PPE advocated by otolaryngology groups is justified. MAIN BODY: Health care workers in China who performed tracheotomy during the SARS-CoV-1 epidemic had 4.15 times greater odds of contracting the virus than controls who did not perform tracheotomy (95% CI 2.75\u20137.54). No other studies provide direct epidemiological evidence of increased aerosolized transmission of viruses during otolaryngology procedures. Experimental evidence has shown that electrocautery, advanced energy devices, open suctioning, and drilling can create aerosolized biological particles. The viral load of COVID-19 is highest in the upper aerodigestive tract, increasing the likelihood that aerosols generated during procedures of the upper aerodigestive tract of infected patients would carry viral material. Cough and normal breathing create aerosols which may increase the risk of transmission during outpatient procedures. A significant proportion of individuals infected with COVID-19 may not have symptoms, raising the likelihood of transmission of the disease to inadequately protected health care workers from patients who do not have probable or confirmed infection. Powered air purifying respirators, if used properly, provide a greater level of filtration than N95 masks and thus may reduce the risk of transmission. CONCLUSION: Direct and indirect evidence suggests that a large number of otolaryngology-head and neck surgery procedures are aerosol generating. Otolaryngologists are likely at high risk of contracting COVID-19 during aerosol generating procedures because they are likely exposed to high viral loads in patients infected with the virus. Based on the precautionary principle, even though the evidence is not definitive, adopting enhanced personal protective equipment protocols is reasonable based on the evidence. Further research is needed to clarify the risk associated with performing various procedures during the COVID-19 pandemic, and the degree to which various personal protective equipment reduces the risk.", "qid": 47, "docid": "hjzlj8k3", "rank": 55, "score": 7.691099166870117}, {"content": "Title: Restructuring the inpatient advanced pharmacy practice experience to reduce the risk of contracting coronavirus disease 2019: Lessons from Saudi Arabia Content: INTRODUCTION: On March 11, 2020, the World Health Organization announced the rapidly spreading epidemic of the coronavirus disease 2019 (COVID\u201019) pandemic. Almost all countries started to take proactive precautionary measures to reduce the risk of contracting the virus. The education sector, including pharmacy education, has been drastically impacted by this pandemic. During the outbreak, many hospitals instructed the health profession's schools to restrict or prevent the presence of their students and interns in their hospitals in an effort to limit the spread of the virus. OBJECTIVES: Constraining the presence of interns in the affiliated hospital has impacted the integrity of delivering the learning outcomes of each clinical rotation. In this paper, we present the experience of four faculty preceptors in restructuring the advanced pharmacy practice experience in different clinical settings, including critical care, infectious diseases, cardiology, and internal medicine, in order to reduce the risk of contracting COVID\u201019 at a large academic medical institution in Saudi Arabia. CONCLUSION: We believe that this experience could provide guidance and insights for other pharmacy schools dealing with this issue during this global pandemic.", "qid": 47, "docid": "55ic2g95", "rank": 56, "score": 7.666999816894531}, {"content": "Title: Restructuring the inpatient advanced pharmacy practice experience to reduce the risk of contracting coronavirus disease 2019: Lessons from Saudi Arabia Content: Introduction: On March 11, 2020, the World Health Organization announced the rapidly spreading epidemic of the coronavirus disease 2019 (COVID-19) pandemic. Almost all countries started to take proactive precautionary measures to reduce the risk of contracting the virus. The education sector, including pharmacy education, has been drastically impacted by this pandemic. During the outbreak, many hospitals instructed the health profession's schools to restrict or prevent the presence of their students and interns in their hospitals in an effort to limit the spread of the virus. Objectives: Constraining the presence of interns in the affiliated hospital has impacted the integrity of delivering the learning outcomes of each clinical rotation. In this paper, we present the experience of four faculty preceptors in restructuring the advanced pharmacy practice experience in different clinical settings, including critical care, infectious diseases, cardiology, and internal medicine, in order to reduce the risk of contracting COVID-19 at a large academic medical institution in Saudi Arabia. Conclusion: We believe that this experience could provide guidance and insights for other pharmacy schools dealing with this issue during this global pandemic.", "qid": 47, "docid": "hrurl6f2", "rank": 57, "score": 7.666998863220215}, {"content": "Title: Reluctance to seek pediatric care during the COVID-19 pandemic and the risks of delayed diagnosis Content: Since the outbreak of COVID-19 pandemic, the number of cases registered worldwide has risen to over 3 million. While COVID-19 per se does not seem to represent a significant threat to the pediatric population, which generally presents a benign course and a low lethality, the current emergency might negatively affect the care of pediatric patients and overall children welfare. In particular, the fear of contracting COVID-19 may determine a delayed access to pediatric emergency facilities. Present report focuses on the experience of The Children Hospital in Alessandria (northern Italy). The authors document a drop in the number of admissions to the emergency department (A&E) during the lock-down. They will also focus on four emblematic cases of pediatric patients who were seen to our A&E in severe conditions. All these cases share a significant diagnostic delay caused by the parents\u2019 reluctance to seek medical attention, seen as a potential risk factor for COVID-19 contagion. None was found positive to all COVID-19 swab or immunologic testing. All in all, our data strongly support the importance of promoting a direct and timely interaction between patients and medical staff, to prevent the fear of COVID-19 from causing more harm than the virus itself.", "qid": 47, "docid": "6ro2deuv", "rank": 58, "score": 7.665299892425537}, {"content": "Title: Reluctance to seek pediatric care during the COVID-19 pandemic and the risks of delayed diagnosis Content: Since the outbreak of COVID-19 pandemic, the number of cases registered worldwide has risen to over 3 million. While COVID-19 per se does not seem to represent a significant threat to the pediatric population, which generally presents a benign course and a low lethality, the current emergency might negatively affect the care of pediatric patients and overall children welfare. In particular, the fear of contracting COVID-19 may determine a delayed access to pediatric emergency facilities. Present report focuses on the experience of The Children Hospital in Alessandria (northern Italy). The authors document a drop in the number of admissions to the emergency department (A&E) during the lock-down. They will also focus on four emblematic cases of pediatric patients who were seen to our A&E in severe conditions. All these cases share a significant diagnostic delay caused by the parents' reluctance to seek medical attention, seen as a potential risk factor for COVID-19 contagion. None was found positive to all COVID-19 swab or immunologic testing. All in all, our data strongly support the importance of promoting a direct and timely interaction between patients and medical staff, to prevent the fear of COVID-19 from causing more harm than the virus itself.", "qid": 47, "docid": "nw106tw2", "rank": 59, "score": 7.665298938751221}, {"content": "Title: Psychosocial impact of COVID-19 Content: BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as \"coronaphobia\", has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- \"COVID-19\", \"SARS-CoV2\", \"Pandemic\", \"Psychology\", \"Psychosocial\", \"Psychitry\", \"marginalized\", \"telemedicine\", \"mental health\", \"quarantine\", \"infodemic\", \"social media\" and\" \"internet\". Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multiplied by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an \"infodemic\" spread via different platforms of social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.", "qid": 47, "docid": "5zg5g77w", "rank": 60, "score": 7.66510009765625}, {"content": "Title: Psychosocial impact of COVID-19 Content: BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as \u201ccoronaphobia\u201d, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- \u201cCOVID-19\u201d, \u201cSARS-CoV2\u201d, \u201cPandemic\u201d, \u201cPsychology\u201d, \u201cPsychosocial\u201d, \u201cPsychitry\u201d, \u201cmarginalized\u201d, \u201ctelemedicine\u201d, \u201cmental health\u201d, \u201cquarantine\u201d, \u201cinfodemic\u201d, \u201csocial media\u201d and\u201d \u201cinternet\u201d. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an \u201cinfodemic\u201d spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.", "qid": 47, "docid": "h0yzj1ro", "rank": 61, "score": 7.665099143981934}, {"content": "Title: Garden-based interventions and early childhood health: a protocol for an umbrella review. Content: BACKGROUND Garden-based interventions have the potential to impact young children's health in a number of ways, including enhancing dietary intake, increasing outdoor physical activity, diversifying the gut microbiome, and promoting general wellbeing. A number of recent systematic reviews have either included or focused on garden-based interventions for young children. However, most prior reviews including young children only focus on one health outcome or one setting, making a full summary of prior research assessing the impact of garden-based interventions nonexistent. As such, this umbrella systematic review aims to synthesize the literature on health outcomes of garden-based interventions for young children. METHODS This protocol outlines the systematic steps we will take to conduct an umbrella review on health-related outcomes of garden-based interventions in children younger than 6 years of age. We will systematically search PubMed, PsycINFO, ERIC, CINAHL, Embase, Scopus, OVID-Agricola, and CAB Direct, including all systematic reviews and meta-analyses fitting the pre-determined inclusion/exclusion criteria. We will double screen at each phase of the review: title/abstract, full text, data extraction, and quality appraisal. We will assess the quality of included reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). Based on the potential for stark variability in what how reviews report child health outcomes, we will analyze the reviews both narratively and quantitatively, reporting summary of findings tables and iteratively mapping the results. This protocol aligns with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement (PRISMA-P). DISCUSSION This umbrella review aims to summarize the role that garden-based interventions play in health promotion for young children. We will focus on a number of diverse child health outcomes in an effort to comprehensively synthesize the evidence to inform future garden-based interventions, research, and policy. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019106848.", "qid": 47, "docid": "njrh6apv", "rank": 62, "score": 7.643799781799316}, {"content": "Title: Therapeutic uncertainties in people with cardiometabolic diseases and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) has been declared a pandemic by the World Health Organization and sent all countries scrambling to review emergency healthcare provisions. There is global evidence of each nation struggling to effectively manage the number of people being diagnosed with the virus. These are testing times which have not been experienced in recent generations and there are a number of insecurities regarding the management of people with COVID-19 and cardiometabolic diseases. This review highlights the current concerns related to COVID-19 and provides advice in terms of the therapeutic uncertainty and potential adverse harms associated with therapy when managing people, particularly those with cardiometabolic diseases, who have contracted or are at increased risk of contracting COVID-19.", "qid": 47, "docid": "j7u0ztqy", "rank": 63, "score": 7.6149001121521}, {"content": "Title: Therapeutic uncertainties in people with cardiometabolic diseases and severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102 or COVID\u201019) Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102 or COVID\u201019) has been declared a pandemic by the World Health Organization and sent all countries scrambling to review emergency healthcare provisions. There is global evidence of each nation struggling to effectively manage the number of people being diagnosed with the virus. These are testing times which have not been experienced in recent generations and there are a number of insecurities regarding the management of people with COVID\u201019 and cardiometabolic diseases. This review highlights the current concerns related to COVID\u201019 and provides advice in terms of the therapeutic uncertainty and potential adverse harms associated with therapy when managing people, particularly those with cardiometabolic diseases, who have contracted or are at increased risk of contracting COVID\u201019.", "qid": 47, "docid": "ykmmtmsn", "rank": 64, "score": 7.614899158477783}, {"content": "Title: The kidney in COVID-19: protagonist or figurant? Content: The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as \"at high risk\" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.", "qid": 47, "docid": "h9v5jqfc", "rank": 65, "score": 7.603300094604492}, {"content": "Title: Economic Recovery Following the COVID-19 Pandemic: Resuming Elective Orthopaedic Surgery and Total Joint Arthroplasty Content: BACKGROUND: The economic effects of the COVID-19 crisis are not like anything the U.S. health care system has ever experienced. METHODS: As we begin to emerge from the peak of the COVID-19 pandemic, we need to plan the sustainable resumption of elective procedures. We must first ensure the safety of our patients and surgical staff. It must be a priority to monitor the availability of supplies for the continued care of patients suffering from COVID-19. As we resume elective orthopedic surgery and total joint arthroplasty, we must begin to reduce expenses by renegotiating vendor contracts, use ambulatory surgery centers and hospital outpatient departments in a safe and effective manner, adhere to strict evidence-based and COVID-19\u2013adjusted practices, and incorporate telemedicine and other technology platforms when feasible for health care systems and orthopedic groups to survive economically. RESULTS: The return to normalcy will be slow and may be different than what we are accustomed to, but we must work together to plan a transition to a more sustainable health care reality which accommodates a COVID-19 world. CONCLUSION: Our goal should be using these lessons to achieve a healthy and successful 2021 fiscal year.", "qid": 47, "docid": "ry7zbp3m", "rank": 66, "score": 7.575399875640869}, {"content": "Title: Economic Recovery After the COVID-19 Pandemic: Resuming Elective Orthopedic Surgery and Total Joint Arthroplasty Content: BACKGROUND: The economic effects of the COVID-19 crisis are not like anything the U.S. health care system has ever experienced. METHODS: As we begin to emerge from the peak of the COVID-19 pandemic, we need to plan the sustainable resumption of elective procedures. We must first ensure the safety of our patients and surgical staff. It must be a priority to monitor the availability of supplies for the continued care of patients suffering from COVID-19. As we resume elective orthopedic surgery and total joint arthroplasty, we must begin to reduce expenses by renegotiating vendor contracts, use ambulatory surgery centers and hospital outpatient departments in a safe and effective manner, adhere to strict evidence-based and COVID-19-adjusted practices, and incorporate telemedicine and other technology platforms when feasible for health care systems and orthopedic groups to survive economically. RESULTS: The return to normalcy will be slow and may be different than what we are accustomed to, but we must work together to plan a transition to a more sustainable health care reality which accommodates a COVID-19 world. CONCLUSION: Our goal should be using these lessons to achieve a healthy and successful 2021 fiscal year.", "qid": 47, "docid": "yts6sxry", "rank": 67, "score": 7.575398921966553}, {"content": "Title: The role of children in transmission of SARS-CoV-2: A rapid review Content: Background: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. Methods: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. Results: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. Conclusions: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. Note: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.", "qid": 47, "docid": "a0ivlwax", "rank": 68, "score": 7.567699909210205}, {"content": "Title: The role of children in transmission of SARS-CoV-2: A rapid review Content: BACKGROUND: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. METHODS: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. RESULTS: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. CONCLUSIONS: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. NOTE: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.", "qid": 47, "docid": "xoi9k314", "rank": 69, "score": 7.567698955535889}, {"content": "Title: In this issue of Occupational Medicine Content: The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.", "qid": 47, "docid": "xqqn1t4e", "rank": 70, "score": 7.5584001541137695}, {"content": "Title: The disproportionate rise in COVID-19 cases among Hispanic/Latinx in disadvantaged communities of Orange County, California: A socioeconomic case-series Content: Background: Recent epidemiological evidence has demonstrated a higher rate of COVID-19 hospitalizations and deaths among minorities. This pattern of race-ethnic disparities emerging throughout the United States raises the question of what social factors may influence spread of a highly transmissible novel coronavirus. The purpose of this study is to describe race-ethnic and socioeconomic disparities associated with COVID-19 in patients in our community in Orange County, California and understand the role of individual-level factors, neighborhood-level factors, and access to care on outcomes. Methods: This is a case-series of COVID-19 patients from the University of California, Irvine (UCI) across six-weeks between 3/12/2020 and 4/22/2020. Note, California's shelter-in-place order began on 3/19/2020. Individual-level factors included race-ethnicity status were recorded. Neighborhood-level factors from census tracts included median household income, mean household size, proportion without a college degree, proportion working from home, and proportion without health insurance were also recorded. Results: A total of 210-patients tested were COVID-19 positive, of which 73.3% (154/210) resided in Orange County. Hispanic/Latinx patients residing in census tracts below the median income demonstrated exponential growth (rate = 55.9%, R2 = 0.9742) during the study period. In addition, there was a significant difference for both race-ethnic (p < 0.001) and income bracket (p = 0.001) distributions prior to and after California's shelter-in-place. In addition, the percentage of individuals residing in neighborhoods with denser households (p = 0.046), lower levels of college graduation (p < 0.001), health insurance coverage (p = 0.01), and ability to work from home (p < 0.001) significantly increased over the same timeframe. Conclusions and Relevance: Our study examines the race-ethnic disparities in Orange County, CA, and highlights vulnerable populations that are at increased risk for contracting COVID-19. Our descriptive case series illustrates that we also need to consider socioeconomic factors, which ultimately set the stage for biological and social disparities.", "qid": 47, "docid": "de6vwlh5", "rank": 71, "score": 7.550000190734863}, {"content": "Title: Translating COVID-19 Evidence to Maximize Physical Therapists\u2019 Impact and Public Health Response Content: Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. Late May, 2020, over 100,000 COVID-19 related deaths were reported in the United State, the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession\u2019s growth and development. The profession has had over a 100-year tradition of responding to epidemics including poliomyelitis; two world wars and geographical regions experiencing conflicts and natural disasters; and the epidemic of noncommunicable diseases (NCDs). The evidence-based role of non-invasive interventions (non-pharmacologic/non-surgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in two primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome (ARDS) in its severe acute stage. ARDS is well familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the COVID-19 care continuum. Second, over 90% of individuals who contract and die from COVID-19 have co-morbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients\u2019 efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum and augment public health initiatives by reducing the impact of the current pandemic.", "qid": 47, "docid": "6i0bmnee", "rank": 72, "score": 7.54640007019043}, {"content": "Title: Translating COVID-19 Evidence to Maximize Physical Therapists' Impact and Public Health Response Content: Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. Late May, 2020, over 100,000 COVID-19 related deaths were reported in the United State, the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession's growth and development. The profession has had over a 100-year tradition of responding to epidemics including poliomyelitis; two world wars and geographical regions experiencing conflicts and natural disasters; and the epidemic of noncommunicable diseases (NCDs). The evidence-based role of non-invasive interventions (non-pharmacologic/non-surgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in two primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome (ARDS) in its severe acute stage. ARDS is well familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the COVID-19 care continuum. Second, over 90% of individuals who contract and die from COVID-19 have co-morbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients' efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum and augment public health initiatives by reducing the impact of the current pandemic.", "qid": 47, "docid": "uo34csav", "rank": 73, "score": 7.546399116516113}, {"content": "Title: Children and the COVID-19 transition: Psychological reflections and suggestions on adapting to the emergency Content: The current period of transition due to COVID-19 emergency may negatively affect the psychological functioning of children and require resources aimed at supporting post-transition adaptation. Few contributions exist which specifically focus on what to do in such circumstances in order to assist the mental health of both children and parents. It seems therefore critical to provide strategies, which support the adjustment of children during the pre-existing and post-transition periods. Furthermore, screening projects are required in order to identify those children with increased levels of emotional and behavioural issues, beyond the COVID-19 transition, in order to plan specific interventions.", "qid": 47, "docid": "9vx482kb", "rank": 74, "score": 7.475100040435791}, {"content": "Title: Covid-19: accelerating recovery Content: Covid-19 infections and related illness and death are rightly at the forefront of our minds. It is critical that we consider how to reduce infections, treat those who are ill and protect health systems. We must, however, also consider how the pandemic is affecting the families of those infected, and how interventions to prevent the spread of the virus come with large negative economic and social consequences. We must begin to identify the ways in which we can soften these blows and recover from the negative consequences over the medium and long-term. We highlight here the importance of moving away the tendency to search for interventions to improve one outcome at a time. It will be essential, particularly in highly resource constrained settings, to look for accelerators, interventions which improve multiple outcomes simultaneously. We discuss how this will be especially important for groups who are at particular risk at this time, including of long-term negative outcomes. These include very young children, adolescents and those who have limited capacity to benefit from narrow interventions given critical needs in multiple domains. Searching for accelerators requires that we take a step back and look to identify common causes of negative outcomes and consider how we might address them. For many countries, recovery from this epidemic will be highly constrained by the limited availability of financial resources. Wise investments will be especially important at this time.", "qid": 47, "docid": "bhlp1acq", "rank": 75, "score": 7.463600158691406}, {"content": "Title: The Choice and Partnership Approach to community mental health and addictions services: a realist-informed scoping review protocol. Content: INTRODUCTION Early identification and appropriate treatment of child and adolescent mental health disorders can often be hampered by patchwork services with poorly planned or unclear pathways. The Choice and Partnership Approach (CAPA) is an evidence-based transformational model of community (community-based or outpatient) mental health and addictions services for children and adolescents that aims to better match services to needs and to improve timely access to care. CAPA has been variably implemented across jurisdictions but has not been comprehensively evaluated for its impact on system and client outcomes. Our research question is, 'To what degree does CAPA work, for whom and under what circumstances?'. The purpose of this review is twofold: (1) to gain an understanding of the extent and outcomes of the implementation of CAPA in community mental health and addictions services; and (2) to identify the role of context as it influences the implementation of CAPA and resulting client and system outcomes. METHODS AND ANALYSIS We will conduct a realist-informed scoping review of the literature related to CAPA in either child and adolescent or adult community mental health and addictions services. Relevant studies, reports and documentation will be identified by searching the following online databases: MEDLINE, Embase, CINAHL, PsycINFO, Academic Search Premier, ERIC, Web of Science, Cochrane, Dissertations Abstracts, NCBI Bookshelf, PubMed Central and the Canadian Health Research Collection. The search strategy was developed by a health sciences library scientist and informed by a multidisciplinary team comprising methodological and content knowledge experts. The search will gather evidence from multiple online databases of peer-reviewed literature and grey literature repositories. All articles will be independently assessed for inclusion by pairs of reviewers. The key themes derived from a thematic analysis of extracted data will be presented in a narrative overview. ETHICS AND DISSEMINATION Research ethics review is not required for this scoping review. The results will be disseminated through meetings with stakeholders (including clients and families, clinicians and decision-makers), conference presentations and peer-reviewed publication. The results of this review will inform an overarching programme of research, policy and quality indicator development to ultimately improve mental health and addictions care and subsequent mental health outcomes for children and adolescents.", "qid": 47, "docid": "dk9ih6w6", "rank": 76, "score": 7.444499969482422}, {"content": "Title: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome Content: This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.", "qid": 47, "docid": "ppod1igx", "rank": 77, "score": 7.441500186920166}, {"content": "Title: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome. Content: This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.", "qid": 47, "docid": "svgknqud", "rank": 78, "score": 7.44149923324585}, {"content": "Title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Content: OBJECTIVES: With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with an asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. METHODS: A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also verified them with the patients and their families. RESULTS: Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not traveled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days two through three of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical nor radiographic abnormalities. All five cases had an increasing level of C-reactive protein. CONCLUSIONS: Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "qid": 47, "docid": "bgoihr3t", "rank": 79, "score": 7.440400123596191}, {"content": "Title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Content: Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "qid": 47, "docid": "pgtvx6wb", "rank": 80, "score": 7.440399169921875}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID-19) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory-confirmed COVID-19. We conducted random-effects meta-analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty-six articles reporting 551 cases of COVID-19 in children (aged 1 day-17.5 years) were included. Eighty-seven percent (95% CI: 77%-95%) of patients had household exposure to COVID-19. The most common symptoms and signs were fever (53%, 95% CI: 45%-61%), cough (39%, 95% CI: 30%-47%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%-28%); however, 18% (95% CI: 11%-27%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%-43%) and ground glass opacities (28%, 95% CI: 18%-39%), but 36% (95% CI: 28%-45%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%-92%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID-19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID-19 case. Children with COVID-19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 47, "docid": "dqjwcm0i", "rank": 81, "score": 7.410600185394287}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta\u2010analysis of 551 laboratory\u2010confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID\u201019) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory\u2010confirmed COVID\u201019. We conducted random\u2010effects meta\u2010analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty\u2010six articles reporting 551 cases of COVID\u201019 in children (aged 1 day\u201017.5 years) were included. Eighty\u2010seven percent (95% CI: 77%\u201095%) of patients had household exposure to COVID\u201019. The most common symptoms and signs were fever (53%, 95% CI: 45%\u201061%), cough (39%, 95% CI: 30%\u201047%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%\u201028%); however, 18% (95% CI: 11%\u201027%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%\u201043%) and ground glass opacities (28%, 95% CI: 18%\u201039%), but 36% (95% CI: 28%\u201045%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%\u201092%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID\u201019 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID\u201019 case. Children with COVID\u201019 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 47, "docid": "hit7rs6q", "rank": 82, "score": 7.410599231719971}, {"content": "Title: Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections during the Covid-19 pandemic in Africa Content: Background: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points. Methods: We used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month Covid-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the Covid-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the Covid-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis. Findings: For every one excess Covid-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 143 (38 - 576) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 58,000 (3,200 - 21,350,000), 52,000 (2,800 - 18,884,000), 2,000 (393 - 12,000), and 157 (41 - 652) respectively. In the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 5 (1 - 21) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 2,000 (131 - 839,000). Interpretation: Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of Covid-19 deaths associated with vaccination clinic visits. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the Covid-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the Covid-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community.", "qid": 47, "docid": "m6qe57he", "rank": 83, "score": 7.406000137329102}, {"content": "Title: Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings Content: BACKGROUND: COVID-19 is a novel coronavirus infection that can cause a severe respiratory illness and has been declared a pandemic by the World Health Organization (WHO). Because children appear to be less severely affected than adults, their imaging appearances have not been extensively reported. OBJECTIVE: To systematically review available literature regarding imaging findings in paediatric cases of COVID-19. MATERIALS AND METHODS: We searched four databases (Medline, Embase, Cochrane, Google Scholar) for articles describing imaging findings in children with COVID-19. We included all modalities, age <18 years, and foreign language articles, using descriptive statistics to identify patterns and locations of imaging findings, and their association with outcomes. RESULTS: Twenty-two articles were included, reporting chest imaging findings in 431 children, of whom 421 (97.7%) underwent CT. Criteria for imaging were lacking. At diagnosis, 143/421 (34.0%) had a normal CT. Abnormalities were more common in the lower lobes and were predominantly unilateral. The most common imaging pattern was ground-glass opacification (159/255, 62.4%). None of the studies described lymphadenopathy, while pleural effusions were rare (three cases). Improvement at follow-up CT imaging (3-15 days later) was seen in 29/100 (29%), remained normal in 25/100 (25%) and progressed in 9/100 (9%). CONCLUSION: CT chest findings in children with COVID-19 are frequently normal or mild. Lower lobes are predominantly affected by patchy ground-glass opacification. Appearances at follow-up remain normal or improve in the majority of children. Chest CT imaging adds little to the further management of the patient and should be reserved for severe cases or for identifying alternative diagnoses.", "qid": 47, "docid": "sbfk60wy", "rank": 84, "score": 7.385799884796143}, {"content": "Title: Electrocardiographic Findings in COVID-19: Insights on Mortality and Underlying Myocardial Processes Content: INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. METHODS: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. RESULTS: 756 patients who presented to a large New York City teaching hospital with COVID-19 underwent an ECG. The mean age was 63.3 \u00b1 16 years, 37% were women, 61% of patients were non-white, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (APC)s (odds ratio (OR)=2.57, 95% confidence interval (CI) 1.23-5.36, p=0.01), a right bundle branch block (RBBB) or intraventricular block (IVB) (OR=2.61, 95% CI 1.32-5.18, p=0.002), ischemic T-wave inversion (OR=3.49, 95% CI 1.56-7.80, p=0.002), and nonspecific repolarization (OR=2.31, 95% CI 1.27-4.21, p=0.006) increased the odds of death. ST elevation was rare (n=5, 0.7%). CONCLUSION: We found that patients with ECG findings of both left sided heart disease (APCs, IVB, repolarization abnormalities) and right sided disease (RBBB) have higher odds of death. ST elevation at presentation was rare.", "qid": 47, "docid": "ggrhfpo0", "rank": 85, "score": 7.382999897003174}, {"content": "Title: COVID-19 - Enacting a \u2018new normal\u2019 for people who use drugs Content: The COVID-19 crisis has magnified existing social, economic and political inequities. People who use drugs are particularly vulnerable due to criminalisation and stigma and often experience underlying health conditions, higher rates of poverty, unemployment and homelessness, as well as a lack of access to vital resources \u2013 putting them at greater risk of infection. On the other hand, COVID-19 presents an opportunity to confront the mistakes of the past and re-negotiate a new social contract. The International Network of People who use Drugs (INPUD) believe that this crisis must be an occasion to rethink the function of punishment, to reform the system and to work towards ending the war on drugs. This commentary presents a set of recommendations to UN agencies, governments, donor agencies, academics and researchers and civil society, challenging these actors to work alongside people who use drugs to enact a new reality based on solidarity and cooperation, protection of health and restoration of rights and dignity and most importantly to mobilise to win the peace.", "qid": 47, "docid": "7pk2mb7m", "rank": 86, "score": 7.382800102233887}, {"content": "Title: Information Resource Orchestration during the COVID-19 Pandemic: A Study of Community Lockdowns in China Content: The outbreak of the COVID-19 pandemic has created significant challenges for people worldwide. To combat the virus, one of the most dramatic measures was the lockdown of 4 billion people in what is believed to be the largest quasi-quarantine in human history. As a response to the call to study information behavior during a global health crisis, we adopted a resource orchestration perspective to investigate six Chinese families who survived the lockdown. We explored how elderly, young and middle-aged individuals and children resourced information and how they adapted their information behavior to emerging online technologies. Two information resource orchestration practices (information resourcing activities and information behavior adaptation activities) and three mechanisms (online emergence and convergence in community resilience, the overcoming of information flow impediments, and the application of absorptive capacity) were identified in the study.", "qid": 47, "docid": "tr1knchk", "rank": 87, "score": 7.362800121307373}, {"content": "Title: COVID-19 in Children in the United States: Intensive Care Admissions, Estimated Total Infected, and Projected Numbers of Severe Pediatric Cases in 2020 Content: IMPORTANCE: A surge in severe cases of COVID-19 (coronavirus disease 2019) in children would present unique challenges for hospitals and public health preparedness efforts in the United States. OBJECTIVE: To provide evidence-based estimates of children infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and projected cumulative numbers of severely ill pediatric COVID-19 cases requiring hospitalization during the US 2020 pandemic. DESIGN: Empirical case projection study. MAIN OUTCOMES AND MEASURES: Adjusted pediatric severity proportions and adjusted pediatric criticality proportions were derived from clinical and spatiotemporal modeling studies of the COVID-19 epidemic in China for the period January-February 2020. Estimates of total children infected with SARS-CoV-2 in the United States through April 6, 2020, were calculated using US pediatric intensive care unit (PICU) cases and the adjusted pediatric criticality proportion. Projected numbers of severely and critically ill children with COVID-19 were derived by applying the adjusted severity and criticality proportions to US population data, under several scenarios of cumulative pediatric infection proportion (CPIP). RESULTS: By April 6, 2020, there were 74 children who had been reported admitted to PICUs in 19 states, reflecting an estimated 176 190 children nationwide infected with SARS-CoV-2 (52 381 infants and toddlers younger than 2 years, 42 857 children aged 2-11 years, and 80 952 children aged 12-17 years). Under a CPIP scenario of 5%, there would be 3.7 million children infected with SARS-CoV-2, 9907 severely ill children requiring hospitalization, and 1086 critically ill children requiring PICU admission. Under a CPIP scenario of 50%, 10 865 children would require PICU admission, 99 073 would require hospitalization for severe pneumonia, and 37.0 million would be infected with SARS-CoV-2. CONCLUSIONS AND RELEVANCE: Because there are 74.0 million children 0 to 17 years old in the United States, the projected numbers of severe cases could overextend available pediatric hospital care resources under several moderate CPIP scenarios for 2020 despite lower severity of COVID-19 in children than in adults.", "qid": 47, "docid": "hdvb2aed", "rank": 88, "score": 7.347700119018555}, {"content": "Title: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Content: Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.", "qid": 47, "docid": "k3bkgf1g", "rank": 89, "score": 7.300899982452393}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in a Renal Transplant Patient Content: Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Transplant patients are particularly at a higher risk of contracting COVID-19 because of their immunosuppressed state, and they have the propensity to develop opportunistic infections. The pre-immunosuppressed state, along with other existing comorbidities, can influence the outcomes of COVID-19 in transplant patients. We describe a case of a renal transplant patient who developed COVID-19. Real-time nucleic acid testing (NAT) should be done in deceased and living donors. The most common management strategy is the modification of immunosuppression along with current experimental strategies for COVID-19.", "qid": 47, "docid": "d9z0m2l8", "rank": 90, "score": 7.291399955749512}, {"content": "Title: Assessing the influence of parental anxiety on childhood anxiety during the COVID-19 pandemic in the United Arab Emirates Content: The COVID-19 pandemic originated in Wuhan, China on December 31st and spread into international borders, leading to a public health crisis and complete shutdown of countries. The strict quarantine measures taken by governments kept a large number of people, around the world, in isolation and affected many aspects of people's lives. These unprecedented changes triggered a wide variety of psychological problems ranging from panic disorders, anxiety and depression. In this study, we aim to explore anxiety levels among parents, teachers and the general community amid the COVID-19 pandemic in the UAE, as well as identify emotional and anxiety disorders in children. Using a web-based cross-sectional survey we collected data from 2,200 self-selected assessed volunteers. Demographic information, knowledge and beliefs about COVID-19, generalized anxiety disorder (GAD) using the (GAD-7) scale , emotional problems in children using the strengths and difficulties questionnaire (SDQ), worry and fear about COVID-19, coping mechanisms and general health information were collected. The overall prevalence of GAD in the general population was 71% with younger people (59.8%) and females (51.7%) reporting the highest levels of anxiety. Parents who were teachers reported the highest percentage of emotional problems in children (26.7%) compared to parents only (14.6%) or teachers only (4.7%). Multivariate logistic regression for GAD-7 score showed that females, participants who felt public fear was justifiable, persons who worried about COVID-19, persons who intended to take the COVID-19 vaccine and smokers were all associated with anxiety. Multivariate logistic regression for SDQ showed parents who had severe anxiety levels were 7 times more likely to report more emotional problems in their children (OR=7.00, 95% CI, 3.45 to 14.0) than less anxious parents. Findings suggest the urgency of policy makers to develop effective screening and coping strategies for parents and teachers and more specifically for vulnerable children.", "qid": 47, "docid": "ihfo778i", "rank": 91, "score": 7.291200160980225}, {"content": "Title: Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient Content: Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.", "qid": 47, "docid": "0kthumgi", "rank": 92, "score": 7.289299964904785}, {"content": "Title: Successful Treatment of Severe COVID-19 Pneumonia in a Liver Transplant Recipient. Content: Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.", "qid": 47, "docid": "uiw9auzx", "rank": 93, "score": 7.289299011230469}, {"content": "Title: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units Content: Importance: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.", "qid": 47, "docid": "6oaks0kl", "rank": 94, "score": 7.277299880981445}, {"content": "Title: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. Content: Importance The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.", "qid": 47, "docid": "bdvnwrd4", "rank": 95, "score": 7.277298927307129}, {"content": "Title: Covid-19, cocooning and vitamin d intake requirements Content: The purpose of this report is to clarify what constitutes best practice on vitamin D supplement use, particularly among older adults, who are at highest risk of Covid-19 On Friday 3rd April, three reports were published on how vitamin D may protect against Covid-19 Two reports are aligned with national and international guidelines on vitamin intake requirements for health: one looked at the importance of vitamin D adequacy in protecting children from respiratory illness but included important advice cautioning against high dose vitamin D;the other is from The Irish Longitudinal Study on Ageing (TILDA) that looked at specific \u2019at risk\u2019 groups for vitamin D deficiency in those over 50 years in a representative sample from the 26 counties TILDA provides a strong evidence base for intervening in older adults with supplemental vitamin D (10 \u00b5g to 20 \u00b5g daily) A third report advises that every adult should take high doses of vitamin D (20 \u00b5g to 50 \u00b5g daily) in order to protect against Covid-19 The authors make no mention about other sources of vitamin D in adults This creates confusion at a time when there is widespread fear and anxiety about the Covid-19 pandemic The following provides a review of the evidence and summarises best practice regarding vitamin D nutrition to protect against Covid-19", "qid": 47, "docid": "ipm58ohm", "rank": 96, "score": 7.275899887084961}, {"content": "Title: Immediate impact of COVID-19 on transplant activity in the Netherlands Content: The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.", "qid": 47, "docid": "863m07vh", "rank": 97, "score": 7.26800012588501}, {"content": "Title: Immediate impact of COVID-19 on transplant activity in the Netherlands Content: Abstract The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.", "qid": 47, "docid": "ae241pmd", "rank": 98, "score": 7.267999172210693}, {"content": "Title: Debate: COVID\u201019 and children in India Content: The COVID\u201019 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world\u2019s children amidst the pandemic which may have lasting consequences. The COVID\u201019 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children\u2019s lives \u2013 their health, development, learning, behaviour and their families\u2019 economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 47, "docid": "8bu6xadf", "rank": 99, "score": 7.236299991607666}, {"content": "Title: Debate: COVID-19 and children in India Content: The COVID-19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world's children amidst the pandemic which may have lasting consequences. The COVID-19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children's lives - their health, development, learning, behaviour and their families' economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 47, "docid": "swgb2tzx", "rank": 100, "score": 7.23629903793335}]}
{"query": "what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic?", "hits": [{"content": "Title: COVID-19 Related School Closings and Risk of Weight Gain Among Children. Content: The COVID-19 pandemic is causing substantial morbidity and mortality, straining health care systems, shutting down economies, and closing school districts. While it is a priority to mitigate its immediate impact, we want to call attention to the pandemic's longer-term effect on children's health: COVID-19, via these school closures, may exacerbate the epidemic of childhood obesity and increase disparities in obesity risk. In many areas of the U.S., the COVID-19 pandemic has closed schools and some of these school systems are not expected to re-open this school year. The experiences in Hong Kong, Taiwan and Singapore suggest that social distancing orders, if lifted after short periods, will have to be periodically re-instated to control COVID-19 flare ups. In short, we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.", "qid": 48, "docid": "x6x6a35w", "rank": 1, "score": 13.667099952697754}, {"content": "Title: Predicting the second wave of COVID-19 in Washtenaw County, MI Content: Marissa Renardy and Denise Kirschner University of Michigan Medical School The COVID-19 pandemic has highlighted the patchwork nature of disease epidemics, with infection spread dynamics varying wildly across countries and across states within the US. These heteroge- neous patterns are also observed within individual states, with patches of concentrated outbreaks. Data is being generated daily at all of these spatial scales, and answers to questions regarded re- opening strategies are desperately needed. Mathematical modeling is useful in exactly these cases, and using modeling at a county scale may be valuable to further predict disease dynamics for the purposes of public health interventions. To explore this issue, we study and predict the spread of COVID-19 in Washtenaw County, MI, the home to University of Michigan, Eastern Michigan University, and Google, as well as serving as a sister city to Detroit, MI where there has been a serious outbreak. Here, we apply a discrete and stochastic network-based modeling framework allowing us to track every individual in the county. In this framework, we construct contact net- works based on synthetic population datasets specific for Washtenaw County that are derived from US Census datasets. We assign individuals to households, workplaces, schools, and group quarters (such as prisons). In addition, we assign casual contacts to each individual at random. Using this framework, we explicitly simulate Michigan-specific government-mandated workplace and school closures as well as social distancing measures. We also perform sensitivity analyses to identify key model parameters and mechanisms contributing to the observed disease burden in the three months following the first observed cases on COVID-19 in Michigan. We then consider several scenarios for relaxing restrictions and reopening workplaces to predict what actions would be most prudent. In particular, we consider the effects of 1) different timings for reopening, and 2) different levels of workplace vs. casual contact re-engagement. Through simulations and sensitivity analyses, we explore mechanisms driving magnitude and timing of a second wave of infections upon re-opening. This model can be adapted to other US counties using synthetic population databases and data specific to those regions.", "qid": 48, "docid": "n1jmqx6m", "rank": 2, "score": 12.199600219726562}, {"content": "Title: The invisible workforce during the COVID-19 pandemic: Family carers at the frontline Content: This is an open letter to acknowledge the essential and increasingly challenging role unpaid family carers are playing in the COVID-19 pandemic. The letter is written by members of the CAREWELL team, a HRB-funded project that aims to promote health and self-care behaviours among working family carers. Family carers provide care to family and friends in the community who need support due to old-age, disability and chronic illness. In many cases, family carers are supporting those who are considered most at risk in this pandemic meaning carers must reduce their own risk of infection in order to protect their dependent family members. The temporary reduction of some home care services, as well as school and creche closures, means that family carers are providing increased levels of care with little or no support. At a time when both worlds of work and care have been dramatically transformed, we wish to shed light on those who are currently balancing paid employment with a family caregiving role. We argue that there is much to be learned from the recent work restrictions that could benefit employees, including working family carers, beyond this pandemic. We also wish to build on the potential positives of a transformed society and encourage policy makers and employers to focus on what is currently being implemented, and to identify which measures could be used to create a bedrock of policies and practices that would offer robust and effective support to family carers. It is hoped that family carers will receive greater recognition for the significant role they play in society, providing essential care and alleviating the strain on health and social care systems, both during and post the COVID-19 pandemic.", "qid": 48, "docid": "b4r0jyjo", "rank": 3, "score": 11.537199974060059}, {"content": "Title: A mathematical model to guide the re-opening of economies during the COVID-19 pandemic Content: Despite rigorous global containment and quarantine efforts, the incidence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19, continues to surge, with more than 12 million laboratory-confirmed cases and over 500,000 deaths worldwide (as of 11 July 2020). Aside from the continued surge in cases and the imperatives of public health concern and saving lives, economic devastation is also mounting with a global depression now seeming inevitable. There is limited attention directed towards people who have recovered from the virus and whether this metric can be useful in guiding when the economy can be re-opened. In this paper, a simpler model is presented in order to guide various countries on the (possible) re-opening of the economy (or re-opening in stages/phases) alongside risk categories and ratios. Factors that need to be considered when applying the model include the healthcare capacity in terms of the number of hospitals, beds and healthcare workers that are available to capacitate this virus. In addition, population size, physical distancing measures, socio-economic disparities, lockdown regulations in each country, and more importantly - the amount and accuracy of testing conducted, is also imperative to consider. Decisions adopted by leaders around the world have the most difficult decision to make (yet), and have to weigh up on what really matters; health or wealth. It is suggested that this model be applied in a number of states/counties and countries in order to gauge the risk of their location being re-opened, by observing their total number of recoveries in proximity to total number of cases.", "qid": 48, "docid": "q5efqr7r", "rank": 4, "score": 11.417200088500977}, {"content": "Title: COVID-19 and the re-opening of schools: a policy maker\u2019s dilemma Content: The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school\u2019s closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school\u2019s closure.", "qid": 48, "docid": "22y5ewq6", "rank": 5, "score": 11.202799797058105}, {"content": "Title: COVID-19 and the re-opening of schools: a policy maker's dilemma Content: The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school's closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school's closure.", "qid": 48, "docid": "5eg7hf6r", "rank": 6, "score": 11.202798843383789}, {"content": "Title: A modelling framework to assess the likely effectiveness of facemasks in combination with 'lock-down' in managing the COVID-19 pandemic Content: COVID-19 is characterized by an infectious presymptomatic period,when newly infected individuals can unwittingly infect others We are interested in what benefits facemasks could offer as a nonpharmaceutical intervention, especially in the settings where high-technology interventions, such as contact tracing using mobile apps or rapid case detection via molecular tests, are not sustainable Here, we report the results of two mathematical models and show that facemask use by the public could make a major contribution to reducing the impact of the COVID-19 pandemic Our intention is to provide a simple modelling framework to examine the dynamics of COVID-19 epidemics when facemasks are worn by the public, with or without imposed 'lock-down' periods Our results are illustrated for a number of plausible values for parameter ranges describing epidemiological processes and mechanistic properties of facemasks, in the absence of current measurements for these values We show that, when facemasks are used by the public all the time (not just from when symptoms first appear), the effective reproduction number, Re, can be decreased below 1, leading to the mitigation of epidemic spread Under certain conditions, when lock-down periods are implemented in combination with 100% facemask use, there is vastly less disease spread, secondary and tertiary waves are flattened and the epidemic is brought under control The effect occurs even when it is assumed that facemasks are only 50% effective at capturing exhaled virus inoculum with an equal or lower efficiency on inhalation Facemask use by the public has been suggested to be ineffective because wearers may touch their facesmore often, thus increasing the probability of contracting COVID-19 For completeness, our models show that facemask adoption provides population-level benefits, even in circumstances where wearers are placed at increased risk At the time of writing, facemask use by the public has not been recommended in many countries, but a recommendation for wearing face-coverings has just been announced for Scotland Even if facemask use began after the start of the first lock-down period, our results show that benefits could still accrue by reducing the risk of the occurrence of further COVID-19 waves We examine the effects of different rates of facemask adoption without lock-down periods and show that, even at lower levels of adoption, benefits accrue to the facemask wearers These analyses may explain why some countries, where adoption of facemask use by the public is around 100%, have experienced significantly lower rates of COVID-19 spread and associated deaths We conclude that facemask use by the public, when used in combination with physical distancing or periods of lock-down, may provide an acceptable way of managing the COVID- 19 pandemic and re-opening economic activity These results are relevant to the developed as well as the developing world, where large numbers of people are resource poor, but fabrication of home-made, effective facemasks is possible A key message from our analyses to aid the widespread adoption of facemasks would be: 'my mask protects you, your mask protects me' [ABSTRACT FROM AUTHOR] Copyright of Proceedings of the Royal Society A: Mathematical, Physical & Engineering Sciences is the property of Royal Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )", "qid": 48, "docid": "30pl5tx3", "rank": 7, "score": 11.043600082397461}, {"content": "Title: Time to restart: A comparative compilation of triage recommendations in dentistry during the Covid \u221219 pandemic Content: BACKGROUND: The novel coronavirus (COVID-19) pandemic has become a enormous challenge for the health care facilitators. It has significantly affected the dental professionals in their clinical practices, hospitals and even dental schools. Due to the risk of cross \u2013 infection involved within in the dental setting, the dental professional is even scared to provide emergent treatment for a patient. AIM: The aim of this comparative review is to throw light on the essential knowledge that a clinician must acquire before triaging a patient, understanding the case definition of COVID-19 and preparedness required before planning to re-open the dental practices. METHODOLOGY: The updated database obtained from various governmental and non-governmental official webpages were rapidly analysed up till May 31, 2020. CONCLUSION: This compilation of recommendations and guidance laid by various authorities across the world will function as a foundation for safer dental practice within the future.", "qid": 48, "docid": "nr252oqb", "rank": 8, "score": 10.438799858093262}, {"content": "Title: Medical students' preference for returning to the clinical setting during the COVID-19 pandemic Content: OBJECTIVES: The Covid-19 pandemic has led to widespread disruptions in the clinical education of medical students. In managing students' return to the clinical setting, medical schools face the challenge of balancing education, service, and risk considerations. To compound this challenge, medical students may prefer not to re-enter during a period of great uncertainty, leading to substantive downstream sequelae on individual, institutional, and national levels. Understanding students' views on resuming clinical experiences, therefore, is an important consideration. The purpose of this study was to assess medical students' preference for re-entering the clinical setting during a pandemic, and to explore personal and environmental characteristics associated with that preference. METHODS: We conducted an electronic survey of currently enrolled medical students of Duke-NUS Medical School in Singapore, less than a month into the pandemic. Survey items were aligned with a conceptual framework related to medical students' preference for returning to the clinical setting. The framework consisted of three domains: 1) non-modifiable demographic information, 2) factors thought to be modifiable through the course of medical education, including burnout, tolerance for ambiguity, motivation, and professionalism, and 3) students' perception of Covid-19 infection risk to self. RESULTS: Approximately one third of 179 students preferred not to return to the clinical setting. Results of a multivariable analysis indicated that compared to this group, the two-thirds of students favouring return showed evidence of greater autonomous (or internal) motivation, a greater sense of professional responsibility, and a lower self-perception of harbouring risk to patients. CONCLUSIONS: Students' preference regarding return to the clinical environment stems from the interplay of several key factors, and is substantively associated with perceptions of professional responsibility and their own potential risk to the healthcare system. Mindfully considering and addressing these issues may help medical schools in their preparation for returning students to the clinical setting.", "qid": 48, "docid": "jv3afofh", "rank": 9, "score": 10.358099937438965}, {"content": "Title: Medical students\u2019 preference for returning to the clinical setting during the COVID\u201019 pandemic Content: OBJECTIVES: The Covid\u201019 pandemic has led to widespread disruptions in the clinical education of medical students. In managing students\u2019 return to the clinical setting, medical schools face the challenge of balancing education, service, and risk considerations. To compound this challenge, medical students may prefer not to re\u2010enter during a period of great uncertainty, leading to substantive downstream sequelae on individual, institutional, and national levels. Understanding students\u2019 views on resuming clinical experiences, therefore, is an important consideration. The purpose of this study was to assess medical students\u2019 preference for re\u2010entering the clinical setting during a pandemic, and to explore personal and environmental characteristics associated with that preference. METHODS: We conducted an electronic survey of currently enrolled medical students of Duke\u2010NUS Medical School in Singapore, less than a month into the pandemic. Survey items were aligned with a conceptual framework related to medical students\u2019 preference for returning to the clinical setting. The framework consisted of three domains: 1) non\u2010modifiable demographic information, 2) factors thought to be modifiable through the course of medical education, including burnout, tolerance for ambiguity, motivation, and professionalism, and 3) students\u2019 perception of Covid\u201019 infection risk to self. RESULTS: Approximately one third of 179 students preferred not to return to the clinical setting. Results of a multivariable analysis indicated that compared to this group, the two\u2010thirds of students favouring return showed evidence of greater autonomous (or internal) motivation, a greater sense of professional responsibility, and a lower self\u2010perception of harbouring risk to patients. CONCLUSIONS: Students\u2019 preference regarding return to the clinical environment stems from the interplay of several key factors, and is substantively associated with perceptions of professional responsibility and their own potential risk to the healthcare system. Mindfully considering and addressing these issues may help medical schools in their preparation for returning students to the clinical setting.", "qid": 48, "docid": "w1he9ebs", "rank": 10, "score": 10.358098983764648}, {"content": "Title: The far side of the COVID-19 epidemic curve: local re-openings based on globally coordinated triggers may work best Content: In the late stages of an epidemic, infections are often sporadic and geographically distributed. Spatially structured stochastic models can capture these important features of disease dynamics, thereby allowing a broader exploration of interventions. Here we develop a stochastic model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission amongst an interconnected group of population centres representing counties, municipalities and districts (collectively, ``counties''). The model is parameterized with demographic, epidemiological, testing, and travel data from the province of Ontario, Canada. We explore the effects of different control strategies after the epidemic curve has been flattened. We compare a local strategy of re-opening (and re-closing, as needed) schools and workplaces county-by-county according to triggers for county-specific infection prevalence, to a global strategy of province-wide re-opening and re-closing according to triggers for province-wide infection prevalence. We find that the local strategy results in far fewer person-days of closure but only slightly more coronavirus disease (COVID-19) cases, even under assumptions of high inter-county travel. However, both cases and person-days lost to closure rise significantly when county triggers are not coordinated by the province and when testing rates vary among counties. Finally, we show that local strategies can also do better in the early epidemic stage but only if testing rates are high and the trigger prevalence is low. Our results suggest that phased plans for re-opening economies on the far side of the COVID-19 epidemic curve should consider preceding larger-scale re-openings with coordinated local re-openings.", "qid": 48, "docid": "rn3aw7wi", "rank": 11, "score": 10.178899765014648}, {"content": "Title: Effective Teaching and Examination Strategies for Undergraduate Learning During COVID-19 School Restrictions Content: On Friday, March 13, 2020, all school teaching in the Republic of Trinidad and Tobago, West Indies was suspended until further notice because of the novel coronavirus COVID-19 pandemic. This immediately jeopardized the completion of course content at the University of the West Indies, St. Augustine campus. This article presents effective teaching and examination strategies that can be utilized in teaching undergraduates during COVID-19 school restrictions. The introductory digital electronics course of the Department of Electrical and Computer Engineering at the University of the West Indies will be utilized to demonstrate the merits of these strategies. The research will focus on demonstrating that the teaching methodologies utilized avoided the student performance from degrading below what has been experienced in the past 5 academic years. Student feedback on the methodology utilized is also incorporated in this article to highlight key benefits gained by students.", "qid": 48, "docid": "g7onopr1", "rank": 12, "score": 10.045100212097168}, {"content": "Title: To catch the sparrow that has flown Content: Like a sparrow that has flown, the sense of safety and invincibility that Americans used to enjoy was weakened by 9/11 and eviscerated by the COVID-19 pandemic. Ripple effects from these events demonstrate the need to equip students with the grit and resilience to deliver public services with compassion in the midst of uncertainty. To do so intertwines two subjects\u2013emotional labor and the public encounter\u2013and together they illuminate what is missing in traditional public administration education. At a time when the certainties of spreadsheets come up short, the public encounter becomes more important. Now is an opportunity to re-center our pedagogy and focus on the holistic nature of public service. Emotion and interpersonal competence are as important as rationality and cognitive competence. With attention to introductory, capstone, leadership, and HR courses, suggestions on how to integrate these subjects are offered.", "qid": 48, "docid": "l0xh4myc", "rank": 13, "score": 10.02400016784668}, {"content": "Title: Homegrown Ultraviolet Germicidal Irradiation for Hospital-Based N95 Decontamination during the COVID-19 Pandemic Content: Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for the 2020 global pandemic and characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, and this risk is mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). The high demand for FFRs is not currently met by global supply chains, potentially placing HCWs at increased exposure risk. Effective FFR decontamination modalities exist, which could maintain respiratory protection for HCWs in the midst of the current pandemic, through the decontamination and re-use of FFRs. Here, we present a locally-implemented ultraviolet-C germicidal irradiation (UVGI)-based FFR decontamination pathway, utilizing a home-built UVGI array assembled entirely with previously existing components available at our institution. We provide recommendations on the construction of similar systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.", "qid": 48, "docid": "zje20bzz", "rank": 14, "score": 10.002900123596191}, {"content": "Title: Planning of School Teaching during COVID-19 Content: More than one billion students are out of school because of Covid-19, forced to a remote learning that has several drawbacks and has been hurriedly arranged; in addition, most countries are currently uncertain on how to plan school activities for the 2020-2021 school year; all of this makes learning and education some of the biggest world issues of the current pandemic. Unfortunately, due to the length of the incubation period of Covid-19, full opening of schools seems to be impractical till a vaccine is available. In order to support the possibility of some in-person learning, we study a mathematical model of the diffusion of the epidemic due to school opening, and evaluate plans aimed at containing the extra Covid-19 cases due to school activities while ensuring an adequate number of in-class learning periods. We consider a SEAIR model with an external source of infection and a suitable loss function; after a realistic parameter selection, we numerically determine optimal school opening strategies by simulated annealing. It turns out that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, are generally optimal. Besides containing Covid-19 diffusion, these solutions could be pedagogically acceptable, and could also become a driving model for the society at large. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200 with the number of Covid-19 cases among the individuals related to the school increasing by about 66%, instead of the about 250% increase that would have been a consequence of full opening.", "qid": 48, "docid": "rd8dqeot", "rank": 15, "score": 9.704899787902832}, {"content": "Title: Shut and re-open: the role of schools in the spread of COVID-19 in Europe Content: We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden, and German states as case studies. By comparing the growth rates in daily hospitalisations or confirmed cases under different interventions, we provide evidence that the effect of school closure is visible as a reduction in the growth rate approximately 9 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. A large-scale reopening of schools while controlling or suppressing the epidemic appears feasible in countries such as Denmark or Norway, where community transmission is generally low. However, school reopening can contribute to significant increases in the growth rate in countries like Germany, where community transmission is relatively high. Our findings underscore the need for a cautious evaluation of reopening strategies that ensure low classroom occupancy and a solid infrastructure to quickly identify and isolate new infections.", "qid": 48, "docid": "r2x3awlw", "rank": 16, "score": 9.475899696350098}, {"content": "Title: Can indoor sports centers be allowed to re-open during the COVID-19 pandemic based on a certificate of equivalence? Content: Within a time span of only a few months, the SARS-CoV-2 virus has managed to spread across the world. This virus can spread by close contact, which includes large droplet spray and inhalation of microscopic droplets, and by indirect contact via contaminated objects. While in most countries, supermarkets have remained open, due to the COVID-19 pandemic, authorities have ordered many other shops, restaurants, bars, music theaters and indoor sports centers to be closed. As part of COVID-19 (semi)lock-down exit strategies, many government authorities are now (May 2020) allowing a gradual re-opening, where sometimes indoor sport centers are last in line to be permitted to re-open. This technical note discusses the challenges in re-opening these facilities and the measures already suggested by some to tackle these challenges. It also elaborates three potential additional measures and based on these additional measures, it suggests the concept of a certificate of equivalence that could allow indoor sports centers with such a certificate to re-open more rapidly. It also attempts to stimulate increased preparedness of indoor sports centers for potential next waves of SARS-CoV-2 as well as future pandemics. It is concluded that fighting situations such as the COVID-19 pandemic and limiting economic damage requires increased collaboration and research by virologists, epidemiologists, microbiologists, aerosol scientists, building physicists, building services engineers and sports scientists.", "qid": 48, "docid": "kne820pv", "rank": 17, "score": 9.385100364685059}, {"content": "Title: Appr\u00e9hender le COVID-19 au fil de l'eau en tant que psychiatre d'enfant et d'adolescent./ [Appreciating COVID-19 as a child and adolescent psychiatrist on the move] Content: COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.", "qid": 48, "docid": "u7dgeqoh", "rank": 18, "score": 9.375}, {"content": "Title: Current Evidence for Minimally Invasive Surgery During the COVID-19 Pandemic and Risk Mitigation Strategies: A Narrative Review Content: Our objective was to review the literature surrounding the risks of viral transmission during laparoscopic surgery and propose mitigation measures to address these risks. SUMMARY BACKGROUND DATA: The SARS-CoV-2 pandemic has caused surgeons the world over to re-evaluate their approach to surgical procedures given concerns over the risk of aerosolization of viral particles and exposure of operating room staff to infection. International society guidelines advise against the use of laparoscopy; however, the evidence on this topic is scant and recommendations are based on the perceived most cautious course of action. METHODS: We conducted a narrative review of the existing literature surrounding the risks of viral transmission during laparoscopic surgery and balance these risks against the benefits of minimally invasive approaches. We also propose mitigation measures to address these risks that we have adopted in our institution. RESULTS AND CONCLUSION: While it is currently assumed that open surgery minimizes operating room staff exposure to the virus, our findings reveal that this may not be the case. A well-informed, evidence-based opinion is critical when making decisions regarding which operative approach to pursue, for the safety and well-being of the patient, the operating room staff, and the healthcare system at large. Minimally invasive surgical approaches offer significant advantages with respect to both patient care, and the mitigation of the risk of viral transmission during surgery, provided the appropriate equipment and expertise are present.", "qid": 48, "docid": "0zj4gm0b", "rank": 19, "score": 9.330699920654297}, {"content": "Title: Current Evidence for Minimally Invasive Surgery During the COVID-19 Pandemic and Risk Mitigation Strategies: A Narrative Review Content: OBJECTIVE: Our objective was to review the literature surrounding the risks of viral transmission during laparoscopic surgery and propose mitigation measures to address these risks. SUMMARY BACKGROUND DATA: The SARS-CoV-2 pandemic has caused surgeons the world over to re-evaluate their approach to surgical procedures given concerns over the risk of aerosolization of viral particles and exposure of operating room staff to infection. International society guidelines advise against the use of laparoscopy; however, the evidence on this topic is scant and recommendations are based on the perceived most cautious course of action. METHODS: We conducted a narrative review of the existing literature surrounding the risks of viral transmission during laparoscopic surgery and balance these risks against the benefits of minimally invasive approaches. We also propose mitigation measures to address these risks that we have adopted in our institution. RESULTS AND CONCLUSION: While it is currently assumed that open surgery minimizes operating room staff exposure to the virus, our findings reveal that this may not be the case. A well-informed, evidence-based opinion is critical when making decisions regarding which operative approach to pursue, for the safety and well-being of the patient, the operating room staff, and the healthcare system at large. Minimally invasive surgical approaches offer significant advantages with respect to both patient care, and the mitigation of the risk of viral transmission during surgery, provided the appropriate equipment and expertise are present.", "qid": 48, "docid": "prkgjvz7", "rank": 20, "score": 9.33069896697998}, {"content": "Title: Paediatric COVID\u201019 admissions in a region with open schools during the two first months of the pandemic Content: According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country\u2010wide school closures by April 1(st) 2020 in an effort to combat the COVID\u201019 pandemic. It\u2019s estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day care centres and schools for children up to 15 years of age remained open. The strategy decision to shift schools to distance learning only for children aged 16 years and older was influenced by multiple factors, including the potential impact on school closures on the availability of the healthcare work force, the increasing evidence of mainly mild infections among children and the potential negative consequences of school closures for younger children.", "qid": 48, "docid": "555e3ndo", "rank": 21, "score": 9.249600410461426}, {"content": "Title: Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave Content: Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.", "qid": 48, "docid": "4sxsyr6k", "rank": 22, "score": 9.249199867248535}, {"content": "Title: Paramedic intubation during a pandemic: Where are the consensus guidelines? Content: There is no denying that paramedic-led intubation is a contentious issue in out-of-hospital care. Guidelines for the management of COVID-19 are developed with both patient-centred care as well as provider safety in mind, with intubation the preferred airway management strategy in patients suspected to have contracted COVID-19 requiring airway protection or invasive ventilation. However, this has re-ignited a debate which began during the Severe Acute Respiratory Syndrome (SARS) outbreak in the early 2000s around whether the benefit of paramedic-led intubation outweighs the risks to providers during a pandemic. The aim of this commentary is to revisit the evidence around paramedic-led intubation and provide a perspective on paramedic-led intubation during the COVID-19 pandemic. It is hoped this will stimulate further discussion around the benefits and risks of paramedic intubation in the setting of a pandemic.", "qid": 48, "docid": "mcleen25", "rank": 23, "score": 9.21720027923584}, {"content": "Title: Children are unlikely to be the main drivers of the COVID\u201019 pandemic \u2013 a systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID\u201019, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID\u201019 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID\u201019 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID\u201019 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS\u2010COV\u20102 virus, which causes COVID\u201019, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID\u201019 mortality rates in older people.", "qid": 48, "docid": "5azti19e", "rank": 24, "score": 9.197799682617188}, {"content": "Title: Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID-19, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID-19 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID-19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID-19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS-COV-2 virus, which causes COVID-19, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID-19 mortality rates in older people.", "qid": 48, "docid": "tm9uso6w", "rank": 25, "score": 9.197798728942871}, {"content": "Title: Nutrition Therapy in Critically Ill Patients With Coronavirus Disease 2019 Content: In the midst of a coronavirus disease 2019 (COVID-19) pandemic, a paucity of data precludes derivation of COVID-19-specific recommendations for nutrition therapy. Until more data are available, focus must be centered on principles of critical care nutrition modified for the constraints of this disease process, ie, COVID-19-relevant recommendations. Delivery of nutrition therapy must include strategies to reduce exposure and spread of disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated, while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone-positioning and extracorporeal membrane oxygenation. Clinicians should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. Although data extrapolated from experience in acute respiratory distress syndrome warrants use of fiber additives and probiotic organisms, the lack of benefit precludes a recommendation for micronutrient supplementation. Practices that increase exposure or contamination of equipment, such as monitoring gastric residual volumes, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging, should be avoided. At all times, strategies for nutrition therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider.", "qid": 48, "docid": "izhmkii0", "rank": 26, "score": 9.17490005493164}, {"content": "Title: Nutrition Therapy in Critically Ill Patients with Coronavirus Disease (COVID\u201019) Content: In the midst of a worldwide pandemic of the Coronavirus Disease 2019 (COVID\u201019), a paucity of data precludes derivation of COVID\u201019\u2010specific recommendations for nutritional therapy. Until more data are available, the focus needs to center on principles of critical care nutrition modified for the constraints of this disease process, i.e., COVID\u201019\u2010relevant recommendations. Delivery of nutritional therapy must include strategies to reduce exposure and spread of the disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone positioning and extracorporeal membrane oxygenation. Clinicians, though, should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. While data extrapolated from experience in Acute Respiratory Distress Syndrome (ARDS) warrants use of fiber additives and probiotic organisms. The lack of demonstrated benefit precludes a recommendation for micronutrient supplementation. Practices which increase exposure or contamination of equipment, such as use of gastric residual volumes as a monitor, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging should be avoided. At all times, strategies for nutritional therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider. This article is protected by copyright. All rights reserved", "qid": 48, "docid": "abzpfdcu", "rank": 27, "score": 9.133000373840332}, {"content": "Title: Nutrition Therapy in Critically Ill Patients with Coronavirus Disease (COVID-19) Content: In the midst of a worldwide pandemic of the Coronavirus Disease 2019 (COVID-19), a paucity of data precludes derivation of COVID-19-specific recommendations for nutritional therapy. Until more data are available, the focus needs to center on principles of critical care nutrition modified for the constraints of this disease process, i.e., COVID-19-relevant recommendations. Delivery of nutritional therapy must include strategies to reduce exposure and spread of the disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone positioning and extracorporeal membrane oxygenation. Clinicians, though, should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. While data extrapolated from experience in Acute Respiratory Distress Syndrome (ARDS) warrants use of fiber additives and probiotic organisms. The lack of demonstrated benefit precludes a recommendation for micronutrient supplementation. Practices which increase exposure or contamination of equipment, such as use of gastric residual volumes as a monitor, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging should be avoided. At all times, strategies for nutritional therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider. This article is protected by copyright. All rights reserved.", "qid": 48, "docid": "bq0y7krf", "rank": 28, "score": 9.132999420166016}, {"content": "Title: Screen time for children and adolescents during the COVID\u201019 pandemic Content: The coronavirus 2019 (COVID\u201019) pandemic has led to laws and policies including national school closures, lockdown or shelter in place laws, and social distancing recommendations that may translate to higher overall screen time among children and adolescents for the duration of these laws and policies. These policies may need to be periodically re\u2010instated to control future COVID\u201019 recurrences or other national emergencies. Excessive screen time is associated with cardiovascular disease risk factors such as obesity, high blood pressure, and insulin resistance because it increases sedentary time and is associated with snacking", "qid": 48, "docid": "bso0gtj1", "rank": 29, "score": 9.121000289916992}, {"content": "Title: Screen time for children and adolescents during the COVID-19 pandemic Content: The coronavirus 2019 (COVID-19) pandemic has led to laws and policies including national school closures, lockdown or shelter in place laws, and social distancing recommendations that may translate to higher overall screen time among children and adolescents for the duration of these laws and policies. These policies may need to be periodically re-instated to control future COVID-19 recurrences or other national emergencies. Excessive screen time is associated with cardiovascular disease risk factors such as obesity, high blood pressure, and insulin resistance because it increases sedentary time and is associated with snacking.", "qid": 48, "docid": "nhjz01k8", "rank": 30, "score": 9.120999336242676}, {"content": "Title: China\u2019s Internationalized Higher Education During Covid-19: Collective Student Autoethnography Content: This article presents 15 autoethnographical texts detailing student experiences at Beijing Normal University in the midst of the Covid-19 pandemic. Contributions have been collected over 6 weeks between 15 February and 1 April 2020, edited by Hejia Wang (assisted by Moses Oladele Ogunniran and Yingying Huang), and supervised by Michael Peters. Through shared in-depth empirical feelings and representations from a wide variety of cultural, historical, and social contexts, the article outlines an answer to the question: How do students, connected virtually but separated physically in an internationalized university, deal with disruption brought about by the Covid-19 pandemic? Student testimonies offer reflections on Covid-19 and Chinese international education, experiences of online teaching and learning, reflections on university coping mechanisms, an account of realities and feelings related to changes in academic life, and discussions on coping strategies in Chinese international higher education. Contributors expose their individual feelings, effects, benefits, challenges, and risk management strategies. Collected at the peak of the Covid-19 pandemic, these testimonies are unable to offer systemic answers to challenges facing the whole world. However, these experiences and feelings will provide important inputs to global discussions about the future of the world, after Covid-19.", "qid": 48, "docid": "wxgs1800", "rank": 31, "score": 9.105199813842773}, {"content": "Title: Resuming elective surgical activity after the COVID-19 wave: what the patients need to know Content: As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.", "qid": 48, "docid": "uwrzpgrt", "rank": 32, "score": 9.064000129699707}, {"content": "Title: Resuming elective surgical activity after the COVID-19 wave: what the patients need to know. Content: As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.", "qid": 48, "docid": "y7do987k", "rank": 33, "score": 9.06399917602539}, {"content": "Title: What are the Underlying Transmission Patterns of COVID-19 Outbreak? \u2013 An Age-specific Social Contact Characterization Content: Abstract Background COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.", "qid": 48, "docid": "hp8pswt7", "rank": 34, "score": 9.058799743652344}, {"content": "Title: What are the Underlying Transmission Patterns of COVID-19 Outbreak? - An Age-specific Social Contact Characterization Content: Background: COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods: In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings: We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation: With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding: General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.", "qid": 48, "docid": "skj6jmsg", "rank": 35, "score": 9.058798789978027}, {"content": "Title: The COVID-19 pandemic: implications for dental education Content: Aim This narrative review aims to report on the impacts of COVID-19 on the provision of dental education in the 67 dental schools in the United States (US). Having set the scene and current challenges, it aims to suggest some strategies to overcome the issues facing dental schools going forward.Background In the US the Occupational Safety and Health Administration classified dentists in the very high risk category because of the potential for exposure to the virus as a result of aerosol generating procedures (AGP). In the last 20 years there have been two previous outbreaks of coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome) which resulted in no long-term changes in the provision of dental education. The recent paper from Wuhan, China described action in the height of the infection but no sustainable actions to deliver dental education going forward.Challenges The challenges identified include: protecting the health of students, faculty and staff; ensuring the continuity and quality of dental education; ensuring confidence in health and safety measures; and keeping up with guidance. There is some variation across the US but most schools have suspended clinical teaching and implemented stay at home policies. Others have implemented social distancing in laboratories including clinical skills. The final challenge is ensuring that students have the teaching, experience and are assessed to ensure the competency of the graduating student.Solutions Technology in teaching and learning offers many opportunities. For didactic teaching distance learning has been implemented. There are 'off the shelf' programmes for teaching and assessment. The development of bespoke content is time consuming and one solution is for schools to share material. Although still requiring social distancing, manikins and haptics offer some opportunities for skills training. The need for excellent information sharing with faculty and students is emphasised.Conclusion Schools should re-evaluate their policies and curricula and incorporate appropriate methods of distance learning permanently into their teaching. Students should have outreach and multi-professional support in order to allow them to assist in the community during public health crises. Finally, gaps have been identified in US dental schools preparedness for pandemics.", "qid": 48, "docid": "d4tu2k7s", "rank": 36, "score": 9.018400192260742}, {"content": "Title: The COVID-19 pandemic: implications for dental education Content: Aim This narrative review aims to report on the impacts of COVID-19 on the provision of dental education in the 67 dental schools in the United States (US). Having set the scene and current challenges, it aims to suggest some strategies to overcome the issues facing dental schools going forward. Background In the US the Occupational Safety and Health Administration classified dentists in the very high risk category because of the potential for exposure to the virus as a result of aerosol generating procedures (AGP). In the last 20 years there have been two previous outbreaks of coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome) which resulted in no long-term changes in the provision of dental education. The recent paper from Wuhan, China described action in the height of the infection but no sustainable actions to deliver dental education going forward. Challenges The challenges identified include: protecting the health of students, faculty and staff; ensuring the continuity and quality of dental education; ensuring confidence in health and safety measures; and keeping up with guidance. There is some variation across the US but most schools have suspended clinical teaching and implemented stay at home policies. Others have implemented social distancing in laboratories including clinical skills. The final challenge is ensuring that students have the teaching, experience and are assessed to ensure the competency of the graduating student. Solutions Technology in teaching and learning offers many opportunities. For didactic teaching distance learning has been implemented. There are 'off the shelf' programmes for teaching and assessment. The development of bespoke content is time consuming and one solution is for schools to share material. Although still requiring social distancing, manikins and haptics offer some opportunities for skills training. The need for excellent information sharing with faculty and students is emphasised. Conclusion Schools should re-evaluate their policies and curricula and incorporate appropriate methods of distance learning permanently into their teaching. Students should have outreach and multi-professional support in order to allow them to assist in the community during public health crises. Finally, gaps have been identified in US dental schools preparedness for pandemics.", "qid": 48, "docid": "nrumr61g", "rank": 37, "score": 9.018399238586426}, {"content": "Title: Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan Content: Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.", "qid": 48, "docid": "3jmxamtj", "rank": 38, "score": 9.001700401306152}, {"content": "Title: SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study Content: BACKGROUND: A SARS-CoV-2 outbreak affecting 52 people from a large school community in Santiago, Chile was identified (March 12), nine days after the first country case. We assessed the magnitude of the outbreak and the role students and staff played using a self-administered antibody detection test and survey. METHODS: The school was closed on March 13, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, IgG/IgM antibody test and survey to a classroom stratified sample of students and all staff from May 4-19. We aimed to determine overall seroprevalence rates by age group, reported symptoms, contact exposure and to explore dynamics of transmission. RESULTS: Antibody positivity rates were 9.9% (95%CI: 8.2-11.8) for 1,009 students and 16.6% (95%CI: 12.1-21.9) for 235 staff. Among students, positivity was associated with younger age (P=0.01), lower grade level (P=0.05), prior RT-PCR positivity (P=0.03), and history of contact with a confirmed case (P<0.001). Among staff, positivity was higher in teachers (P=0.01) and in those previously RT-PCR positive (P<0.001). Excluding RT-PCR positive individuals, antibody positivity was associated with fever in adults and children (P=0.02; P=0.002), abdominal pain in children (P=0.001), and chest pain in adults (P=0.02). Within antibody positive individuals, 40% of students and 18% of staff reported no symptoms (P=0.01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at higher infection risk, likely because index case(s) were teachers and/or parents from preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school re-openings.", "qid": 48, "docid": "lm29yshl", "rank": 39, "score": 8.959500312805176}, {"content": "Title: SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study. Content: BACKGROUND A SARS-CoV-2 outbreak affecting 52 people from a large school community in Santiago, Chile was identified (March 12), nine days after the first country case. We assessed the magnitude of the outbreak and the role students and staff played using a self-administered antibody detection test and survey. METHODS The school was closed on March 13, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, IgG/IgM antibody test and survey to a classroom stratified sample of students and all staff from May 4-19. We aimed to determine overall seroprevalence rates by age group, reported symptoms, contact exposure and to explore dynamics of transmission. RESULTS Antibody positivity rates were 9.9% (95%CI: 8.2-11.8) for 1,009 students and 16.6% (95%CI: 12.1-21.9) for 235 staff. Among students, positivity was associated with younger age (P=0.01), lower grade level (P=0.05), prior RT-PCR positivity (P=0.03), and history of contact with a confirmed case (P<0.001). Among staff, positivity was higher in teachers (P=0.01) and in those previously RT-PCR positive (P<0.001). Excluding RT-PCR positive individuals, antibody positivity was associated with fever in adults and children (P=0.02; P=0.002), abdominal pain in children (P=0.001), and chest pain in adults (P=0.02). Within antibody positive individuals, 40% of students and 18% of staff reported no symptoms (P=0.01). CONCLUSIONS Teachers were more affected during the outbreak and younger children were at higher infection risk, likely because index case(s) were teachers and/or parents from preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school re-openings.", "qid": 48, "docid": "wox7pnkr", "rank": 40, "score": 8.95949935913086}, {"content": "Title: A Letter to the Future AWWA Content: Dear Future AWWA Members, I'm writing to you on the 139th birthday of the American Water Works Association, and what a strange time it is We are in the midst of a global pandemic A disease called COVID\u201019 is spreading so quickly that we are running short on hospital beds and people are hoarding toilet paper At this moment, the United States has more confirmed cases than any other country and Canada is ranked 15th But I am not writing to tell you about the tragedy of COVID\u201019;I imagine the history books will capture that This is a letter about how today's water professionals are rising to the challenge through their selfless and often uncelebrated acts of courage They are building on the legacy of water professionals throughout AWWA's history, and I wish you were here to witness it As you\u2014the future AWWA\u2014look back on spring 2020, you will clearly see how access to safe, reliable water was critical in halting the spread of COVID\u201019 The simplest example I can provide is handwashing The practice of handwashing for at least 20 seconds, with plenty of soap, has never seemed so important Now, we are a society uniformly obsessed with washing our hands Because tap water is critical to personal hygiene and protecting the public's health, the US Environmental Protection Agency this week sent a letter to all governors, reminding them that water utility workers and water sector businesses that support water utilities should be considered \u201cessential\u201d as communities impose orders to keep people at home And in another sign of the essential nature of water service in a public health crisis, utilities are suspending water shutoffs and, in many cases, restoring service to customers who had previously been shut off But it isn't these policy decisions I hope you'll remember It's the exemplary\u2014and yes, courageous\u2014commitment of your predecessors in the water profession Each day, water professionals are delivering safe water to their communities and then cleaning the wastewater before returning it to the environment Never has this daily routine seemed more extraordinary These days, we are all being asked to participate in \u201csocial distancing,\u201d a term that most had never heard of before COVID\u201019 As schools and restaurants close and citizens are ordered to stay at home, your predecessors in the water profession continue to do what it takes to keep the water flowing, whether that is repairing mains, unclogging sewer lines (you can't imagine what some people do in the absence of toilet paper!), or ensuring treatment equipment is functioning properly Many water professionals are stationed 24/7 at treatment plants They are living apart from their own families so they can protect all of our families The ongoing pandemic has given our society new appreciation for the work of health professionals, police, and other first responders I would say that water professionals are not only first responders, but \u201ceveryday\u201d responders They are the super\u2010heroes we don't need to summon because they are already on the scene I am certain that in time we will be able to return to a more normal state, where a handshake is a handshake and not an elbow bump And when we do, I hope that we\u2014and the people who live in the communities we serve\u2014remember that water is critical to everything we care about and that it played a crucial role in eliminating COVID\u201019 It is not an overstatement to say that others\u2019 lives were in the hands of water professionals during the pandemic Poet and philosopher George Santayana is known for saying, \u201cThose who cannot remember the past are condemned to repeat it \u201d In this case, however, it would be wise to remember and repeat selfless acts like those of water professionals facing COVID\u201019 in the spring of 2020 In closing, Happy Birthday, AWWA, and my thanks to all who are members today and in the future Your commitment to the legacy of safe and reliable water service is, quite literally, life\u2010saving Sincerely, David B LaFrance Chief Executive Officer, American Water orks Association", "qid": 48, "docid": "sk86rbap", "rank": 41, "score": 8.859600067138672}, {"content": "Title: Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position Content: The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk-benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk-benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.", "qid": 48, "docid": "3ryondlt", "rank": 42, "score": 8.84749984741211}, {"content": "Title: Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position Content: The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk\u2013benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk\u2013benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.", "qid": 48, "docid": "vpz3o29f", "rank": 43, "score": 8.847498893737793}, {"content": "Title: Mathematic modeling of COVID-19 in the United States Content: COVID-19, the worst pandemic in 100 years, has rapidly spread to the entire world in 2 months since its early report in January 2020. Based on the publicly available data sources, we developed a simple mathematic modeling approach to track the outbreaks of COVID-19 in the US and three selected states: New York, Michigan and California. The same approach is applicable to other regions or countries. We hope our work can stimulate more effort in understanding how an outbreak is developing and how big a scope it can be and in what kind of time framework. Such information is critical for outbreak control, resource utilization and re-opening of the normal daily life to citizens in the affected community.", "qid": 48, "docid": "kdsbw4ji", "rank": 44, "score": 8.83240032196045}, {"content": "Title: The effect of extended closure of red-light areas on COVID-19 transmission in India Content: The novel coronavirus disease (COVID-19) pandemic has resulted in over 200,000 cases in India. Thus far, India has implemented lockdown measures to curb disease transmission. However, commercial sex work in red-light areas (RLAs) has potential to lead to COVID-19 resurgence after lockdown. We developed a model of COVID-19 transmission in RLAs, evaluating the impact of extended RLA closure compared with RLA reopening on cases, hospitalizations, and mortality rates within the RLAs of five major Indian cities, within the cities, and across India. Closure lowered transmission at all scales. More than 90% of cumulative cases and deaths among RLA residents of Kolkata, Pune, and Nagpur could be averted by the time the epidemic would peak under a re-opening scenario. Across India, extended closure of RLAs would benefit the population at large, delaying the peak of COVID-19 cases by 8 to 23 days, and avert 32% to 60.2% of cumulative cases and 43% to 67.6% of cumulative deaths at the peak of the epidemic. Extended closure of RLAs until better prevention and treatment strategies are developed would benefit public health in India.", "qid": 48, "docid": "wjpi5uvz", "rank": 45, "score": 8.79580020904541}, {"content": "Title: Reorganization of Medical Oncology Departments during COVID-19 Pandemic: a Nationwide Italian Survey Content: Abstract The novel severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) pandemic is a global health problem, which started to affect China by the end of year 2019. In Europe, Italy has faced this novel disease entity (named COVID-19) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits, and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during pandemic.", "qid": 48, "docid": "4pvk3fqn", "rank": 46, "score": 8.779399871826172}, {"content": "Title: Geospatially Referenced Demographic Agent-Based Modeling of SARS-CoV-2-Infection (COVID-19) Dynamics and Mitigation Effects in a Real-world Community Content: Re-opening societies and economies across the globe following the initial wave of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic requires scientifically-guided decision processes and policy development. Public health authorities now consider it highly likely that transmission of SARS-CoV-2 and COVID-19 will follow a pattern of seasonal circulation globally. To guide mitigation strategies and tactics in a location-specific manner, accurate simulation of prolonged or intermittent patterns of social/physical distancing is required in order to prevent healthcare systems and communities from collapsing. It is equally important to capture the stochastic appearance of individual transmission events. Traditional epidemiological/statistical models cannot make predictions in a geospatial temporal manner based on human individuals in a community. Thus, the challenge is to conduct spatio-temporal simulations of transmission chains with real-world geospatial and georeferenced information of the dynamics of the disease and the effect of different mitigation strategies such as isolation of infected individuals or location closures. Here, we present a stochastic, geospatially referenced and demography-specific agent-based model with agents representing human beings and include information on age, household composition, daily occupation and schedule, risk factors, and other relevant properties. Physical encounters between humans are modeled in a time-dependent georeferenced network of the population. The model (GERDA-1) can predict infection dynamics under normal conditions and test the effect of different mitigation scenarios such as school closures, reduced social contacts as well as closure or reopening of public/work spaces. Specifically, it also includes the fate and influence of health care workers and their access to protective gear. Key predictions so far entail: (i) the effect of specific groups on the spreading, specifically that children in school contribute substantially to distribution. (ii) the result of reopening society depends crucially on how strict the measures have been during lock-down. (iii) the outcome of reopening is a stochastic process - in the majority of cases, we must expect a second wave, in some cases not. To the best of our best knowledge, the GERDA-1 model is the first model able to predict a bimodal behavior of SARS-Cov-2 infection dynamics. Given the criticality of the global situation, informing the scientific community, decision makers and the general public seems prudent. Therefore, we here provide a pre-print of the GERDA-1 model together with a first set of predictions and analyses as work in progress.", "qid": 48, "docid": "k9cpbszs", "rank": 47, "score": 8.779000282287598}, {"content": "Title: Guidance and Patient Instructions for Proning and Repositioning of Awake, Non\u2010Intubated COVID\u201019 Patients Content: Prior studies on proning awake, non\u2010intubated patients with hypoxemic acute respiratory failure, as well as evolving study of similar COVID\u201019 patients, coupled with experience and dramatic anecdotal evidence from the COVID\u201019 pandemic, suggest the importance of proning all such patients with COVID\u201019 to improve oxygenation and reduce respiratory effort. Literature and experience from healthcare teams in the midst of the pandemic suggest that any COVID\u201019 patients with respiratory compromise severe enough to warrant admission should be considered for proning. We additionally suggest these patients should be considered for proning as well as ongoing patient re\u2010positioning (e.g. right lateral decubitus, seated, and left lateral decubitus positions). Figure 1 represents the proning and positioning instructions developed at New York City Health + Hospitals/Elmhurst, a large, inner\u2010city, tertiary public hospital in the epicenter of the COVID\u201019 pandemic in New York City, and later adapted and utilized at facilities across the United States.", "qid": 48, "docid": "cea0nt8z", "rank": 48, "score": 8.773300170898438}, {"content": "Title: Guidance and Patient Instructions for Proning and Repositioning of Awake, Non-Intubated COVID-19 Patients Content: Prior studies on proning awake, non-intubated patients with hypoxemic acute respiratory failure, as well as evolving study of similar COVID-19 patients, coupled with experience and dramatic anecdotal evidence from the COVID-19 pandemic, suggest the importance of proning all such patients with COVID-19 to improve oxygenation and reduce respiratory effort. Literature and experience from healthcare teams in the midst of the pandemic suggest that any COVID-19 patients with respiratory compromise severe enough to warrant admission should be considered for proning. We additionally suggest these patients should be considered for proning as well as ongoing patient re-positioning (e.g. right lateral decubitus, seated, and left lateral decubitus positions). Figure 1 represents the proning and positioning instructions developed at New York City Health + Hospitals/Elmhurst, a large, inner-city, tertiary public hospital in the epicenter of the COVID-19 pandemic in New York City, and later adapted and utilized at facilities across the United States.", "qid": 48, "docid": "lqdormg7", "rank": 49, "score": 8.773299217224121}, {"content": "Title: Postdigital Research in the Time of Covid-19 Content: The First 80 Days of Covid-19 The first case of the coronavirus disease, Covid-19, was officially reported from Wuhan, China, on 31 December 2019 (World Health Organization 2020a) The coronavirus disease had initially been compared with an ordinary flu, and Dr Li Wenliang, who raised the alarm in the early days of the outbreak, was investigated by the Chinese police and the Public Security Bureau for \u2018spreading rumours\u2019 Yet it soon became obvious that Covid-19 is far more dangerous than the flu, and Dr Li Wenliang, aged 33, died of the infection on 7 February 2020 (Hegarty 2020) In spite of their harsh initial reactions to Dr Li Wenliang\u2019s alleged whistleblowing, Chinese authorities soon exhibited remarkable determination in containing the virus By late January, they quarantined the city of Wuhan (11 million inhabitants) and several other areas affecting over 60 million of people \u2018Since February 18, China has reported the number of recovered cases is vastly outpacing the number of new confirmed cases each day \u2019 (Roper 2020) In the meantime, the coronavirus has crossed the borders of China, and Western countries have been much slower in their response On 11 March, the World Health Organization \u2018declared COVID-19 a pandemic, pointing to the over 118,000 cases of the coronavirus illness in over 110 countries and territories around the world and the sustained risk of further global spread\u2019 (Ducharme 2020) and on 13 March, \u2018[i] nternational health officials said Friday that Europe has become the epicenter of the coronavirus pandemic, as the continent is now producing more new cases each day than China did at the height of its crisis\u2019 (Coote and Jacobson 2020) In popular media, the Covid-19 pandemic has started an infodemic of unprecedented scale;fake news and bullshit flourish alongside credible information from sources such as the World Health Organization In the context of research, the Covid-19 pandemic has initiated historically unprecedented levels of collaboration and openness, prompting some authors to suggest that \u2018[w] hen the story of the coronavirus (2019-nCOV) is finally written, it might well become a template for the utopian dream of open science \u2014 where research data is shared freely, unrestrained by competition, paywalls and patents\u2019 (Crowe 2020) Worldwide closures of schools and universities have pushed millions of students and teachers online, bringing decades of experience in the field under the public eye (Bates 2020) Commentators compare Chinese and Western responses to the crisis, often under bombastic titles such as \u2018Coronavirus and the Clash of Civilizations\u2019 (Ma\u00e7\u00e3es 2020) Political scientists discuss whether the pandemic is an argument for total dismissal of capitalism or just a passing aberration in its functioning (Roberts 2020) Economists advise us to prepare the new recession (Elliott 2020) Sociologists see worldwide border closures as an anti-globalization experiment (Peters et al 2020), and philosophers go back to questions pertaining to human nature Worldwide governments are responding in radically different ways\u2014the government of Montenegro has closed down the whole country before it registered the first patient within its borders (World Health Organization 2020b), while the UK has opted for a laissez faire approach which is hoped to result in herd immunity (Dunn and Kahn 2020) From official news to social networks, everyone and anyone has something to contribute to these debates, creating an infodemic which will be analysed long after Covid-19 is gone As I write these words on 16 March 2020 from self-isolation in my flat in Zagreb, Croatia, the future of the pandemic is unclear We have no idea what percentage of the global population will be affected by the virus, whether the virus will mutate, how many people the virus might kill, and what might happen with our politics and economy after the pandemic is gone At this point, we need to develop immediate measures to protect ourselves individually and collectively\u2014weed out reliable information, self-isolate, reduce panic, develop educated guesses and emergency plans However, these urgent measures cannot arrive from thin air, and it is just as important to step back and take a birds-eye, longue dur\u00e9e view at the pandemic While doctors, nurses, politicians, food suppliers, and many other brave people self-sacrifice to support our daily survival, this editorial argues that academics have a unique opportunity, and a moral duty, to immediately start conducting in-depth studies of current events [truncated]", "qid": 48, "docid": "wdnnjlcw", "rank": 50, "score": 8.771699905395508}, {"content": "Title: Deliberation, Citizen Science and Covid\u201019 Content: Rather than aiming to produce more \u2018rational\u2019 or more \u2018other\u2010regarding\u2019 citizen judgements (the outcome of which is uncertain), deliberative democratic exercises should be re\u2010designed to maximise democratic participation. To do this, they must involve citizens and experts, a novel arrangement that will benefit both cohorts. For the former, a more inclusive form of deliberation will offer an opportunity to contribute to political discussion and be listened to by people with political or policy\u2010based authority. For the latter, it will provide a venue through which expertise can be brought to bear on democratic decision making without risk of scapegoating or politicisation. More broadly, deliberation that prioritises dialogue (over, say, opinion change) affirms the principle that political decisions reflect value judgements rather than technically \u2018right\u2019 or technically \u2018wrong\u2019 answers\u2014judgements that are legitimate if arrived at through discussion involving the people due to be affected by the resultant policy. This article sets out the advantages of this form of deliberation\u2014which bears some similarity to certain types of citizen science\u2014in the context of the UK government\u2019s responses to Covid\u201019; both the confused decision making evident to date, and the forthcoming re\u2010opening phases that will prioritise or advantage some constituencies over others.", "qid": 48, "docid": "4vls1rph", "rank": 51, "score": 8.769100189208984}, {"content": "Title: The great opportunity: Evolutionary applications to medicine and public health Content: Evolutionary biology is an essential basic science for medicine, but few doctors and medical researchers are familiar with its most relevant principles. Most medical schools have geneticists who understand evolution, but few have even one evolutionary biologist to suggest other possible applications. The canyon between evolutionary biology and medicine is wide. The question is whether they offer each other enough to make bridge building worthwhile. What benefits could be expected if evolution were brought fully to bear on the problems of medicine? How would studying medical problems advance evolutionary research? Do doctors need to learn evolution, or is it valuable mainly for researchers? What practical steps will promote the application of evolutionary biology in the areas of medicine where it offers the most? To address these questions, we review current and potential applications of evolutionary biology to medicine and public health. Some evolutionary technologies, such as population genetics, serial transfer production of live vaccines, and phylogenetic analysis, have been widely applied. Other areas, such as infectious disease and aging research, illustrate the dramatic recent progress made possible by evolutionary insights. In still other areas, such as epidemiology, psychiatry, and understanding the regulation of bodily defenses, applying evolutionary principles remains an open opportunity. In addition to the utility of specific applications, an evolutionary perspective fundamentally challenges the prevalent but fundamentally incorrect metaphor of the body as a machine designed by an engineer. Bodies are vulnerable to disease \u2013 and remarkably resilient \u2013 precisely because they are not machines built from a plan. They are, instead, bundles of compromises shaped by natural selection in small increments to maximize reproduction, not health. Understanding the body as a product of natural selection, not design, offers new research questions and a framework for making medical education more coherent. We conclude with recommendations for actions that would better connect evolutionary biology and medicine in ways that will benefit public health. It is our hope that faculty and students will send this article to their undergraduate and medical school Deans, and that this will initiate discussions about the gap, the great opportunity, and action plans to bring the full power of evolutionary biology to bear on human health problems.", "qid": 48, "docid": "sdumq61z", "rank": 52, "score": 8.761099815368652}, {"content": "Title: Reorganisation of medical oncology departments during the novel coronavirus disease-19 pandemic: a nationwide Italian survey Content: The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic.", "qid": 48, "docid": "x7y2xgmo", "rank": 53, "score": 8.75220012664795}, {"content": "Title: Filling in the gaps. Content: The COVID-19 pandemic, and our response to it, has created many voids in our lives, with no-one spared of its effects. As a result, we have all looked for, and found ways to fill in the gaps. In the midst of the epidemic, with healthcare providers in New York City pushed to the extremes of what can be asked of them, they have found ways to bridge the gulf between how they were trained to practice medicine, and what they are being asked to do now.", "qid": 48, "docid": "0aommdzm", "rank": 54, "score": 8.751999855041504}, {"content": "Title: Filling in the gaps Content: The COVID-19 pandemic, and our response to it, has created many voids in our lives, with no-one spared of its effects. As a result, we have all looked for, and found ways to fill in the gaps. In the midst of the epidemic, with healthcare providers in New York City pushed to the extremes of what can be asked of them, they have found ways to bridge the gulf between how they were trained to practice medicine, and what they are being asked to do now.", "qid": 48, "docid": "12kq1sem", "rank": 55, "score": 8.751998901367188}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 48, "docid": "gnaubzah", "rank": 56, "score": 8.730600357055664}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 48, "docid": "hlhhvmtu", "rank": 57, "score": 8.730599403381348}, {"content": "Title: COVID-19: ensuring our medical equipment can meet the challenge. Content: To predict the spread of coronavirus disease globally and consequently prepare the hospital facilities with the required technology is a challenge. The availability of essential medical equipment to support patients affected by Covid-19 is globally limited. AREAS COVERED This perspective gives a technical view of the pandemic focusing on the main actions taken by regulatory agencies to cope with the shortage of devices. The risk/benefit assessment and the main infection control policies in the clinical practices are also looked at. EXPERT OPINION Regulatory agencies have amended their medical devices directives to address the pandemic, but each in a different way. In this exceptional situation scientist and technology experts in collaboration with medical specialists should work together to re-assess the risk analysis on medical equipment management and their use and re-use in this context with the aim to improve global healthcare. Every effort must be made to provide the necessary devices at least with the minimum acceptable performances for Covid-19 patients while maintaining a high standard of safety for users. The aim of the present manuscript is to highlight the technical challenges in order to prevent, through targeted actions, operating standards from falling below the standards of care due to a lack of medical devices.", "qid": 48, "docid": "0scjnqop", "rank": 58, "score": 8.726200103759766}, {"content": "Title: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3\u00b71 million individuals across 1\u00b73 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28\u00b78% (95% CI 28\u00b75\u201329\u00b71) of the health-care workforce needing to provide care for children aged 3\u201312 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15\u00b70% (14\u00b78\u201315\u00b72) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15\u00b70% case reduction from school closings and 2\u00b70% baseline mortality rate, a 15\u00b70% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17\u00b76% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2\u00b700% to 2\u00b735% when the health-care workforce declines by 15\u00b70%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.", "qid": 48, "docid": "517s290b", "rank": 59, "score": 8.7253999710083}, {"content": "Title: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3\u00b71 million individuals across 1\u00b73 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28\u00b78% (95% CI 28\u00b75-29\u00b71) of the health-care workforce needing to provide care for children aged 3-12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15\u00b70% (14\u00b78-15\u00b72) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15\u00b70% case reduction from school closings and 2\u00b70% baseline mortality rate, a 15\u00b70% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17\u00b76% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2\u00b700% to 2\u00b735% when the health-care workforce declines by 15\u00b70%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.", "qid": 48, "docid": "xgjd961x", "rank": 60, "score": 8.725399017333984}, {"content": "Title: School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review Content: In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.", "qid": 48, "docid": "wsn7y3wr", "rank": 61, "score": 8.707200050354004}, {"content": "Title: School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review Content: In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2\u20134% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.", "qid": 48, "docid": "y2zcwcic", "rank": 62, "score": 8.707199096679688}, {"content": "Title: COVID-19: How to Relax Social Distancing If You Must Content: Following the April 16, 2020 release of the Opening Up America Again guidelines for relaxing COVID-19 social distancing policies, local leaders are concerned about future pandemic waves and lack robust strategies for tracking and suppressing transmission. Here, we present a framework for monitoring COVID-19 hospitalization data to project risks and trigger shelter-in-place orders to prevent overwhelming healthcare surges while minimizing the duration of costly lockdowns. Assuming the relaxation of social distancing increases the risk of infection ten-fold, the optimal strategy for Austin, Texas--the fastest-growing large city in the US--will trigger a total of 135 [90% prediction interval: 126-141] days of sheltering, allow schools to open in the fall, and result in an expected 2929 deaths [90% prediction interval: 2837-3026] by September 2021, which is 29% the annual mortality rate. In the months ahead, policy makers are likely to face difficult choices and the extent of public restraint and cocooning of vulnerable populations may save or cost thousands of lives.", "qid": 48, "docid": "njxqf8bn", "rank": 63, "score": 8.665599822998047}, {"content": "Title: Challenges and burden of the Coronavirus 2019 (COVID-19) pandemic for child and adolescent mental health: a narrative review to highlight clinical and research needs in the acute phase and the long return to normality Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) is profoundly affecting life around the globe. Isolation, contact restrictions and economic shutdown impose a complete change to the psychosocial environment in affected countries. These measures have the potential to threaten the mental health of children and adolescents significantly. Even though the current crisis can bring with it opportunities for personal growth and family cohesion, disadvantages may outweigh these benefits. Anxiety, lack of peer contact and reduced opportunities for stress regulation are main concerns. Another main threat is an increased risk for parental mental illness, domestic violence and child maltreatment. Especially for children and adolescents with special needs or disadvantages, such as disabilities, trauma experiences, already existing mental health problems, migrant background and low socioeconomic status, this may be a particularly challenging time. To maintain regular and emergency child and adolescent psychiatric treatment during the pandemic is a major challenge but is necessary for limiting long-term consequences for the mental health of children and adolescents. Urgent research questions comprise understanding the mental health effects of social distancing and economic pressure, identifying risk and resilience factors, and preventing long-term consequences, including\u2014but not restricted to\u2014child maltreatment. The efficacy of telepsychiatry is another highly relevant issue is to evaluate the efficacy of telehealth and perfect its applications to child and adolescent psychiatry. CONCLUSION: There are numerous mental health threats associated with the current pandemic and subsequent restrictions. Child and adolescent psychiatrists must ensure continuity of care during all phases of the pandemic. COVID-19-associated mental health risks will disproportionately hit children and adolescents who are already disadvantaged and marginalized. Research is needed to assess the implications of policies enacted to contain the pandemic on mental health of children and adolescents, and to estimate the risk/benefit ratio of measures such as home schooling, in order to be better prepared for future developments.", "qid": 48, "docid": "wls59o2w", "rank": 64, "score": 8.661399841308594}, {"content": "Title: Impact of small-area lockdowns for the control of the COVID-19 pandemic Content: Background Countries confronting the COVID-19 pandemic are implementing different social distancing strategies. We evaluated the impact of small-area lockdowns in Chile, aimed to reduce viral transmission while minimizing the population disrupted. The effectiveness of this intervention on the outbreak control is unknown. Methods A natural experiment assessing the impact of small-area lockdowns between February 15th and April 25th, 2020. We used mobility data and official governmental reports to compare regions with small-area lockdowns versus regions without. The primary outcome was the mean difference in the effective reproductive number (Re) of COVID-19. Secondary outcomes were changes in mobility indicators. We used quasi-experimental methods for the analysis and examined the impact of other concurrent public health interventions to disentangle their effects. Results Small-area lockdown produced a sizable reduction in human mobility, equivalent to an 11.4% reduction (95%CI -14.4% to -8.38%) in public transport and similar effects in other mobility indicators. Ten days after implementation, the small-area lockdown produced a reduction of the effective reproductive number (Re) of 0.86 (95%CI -1.70 to -0.02). School and university closures, implemented earlier, led to a 40% reduction in urban mobility. Closure of educational institutions resulted in an even greater Re reduction compared with small-area lockdowns. Conclusions Small-area lockdowns produced a reduction in mobility and viral transmission, but the effects were smaller than the early closures of schools and universities. Small-area lockdowns may have a relevant supporting role in reducing SARS-CoV-2 transmission and could be useful for countries considering scaling-down stricter social distancing interventions.", "qid": 48, "docid": "8qr1yp86", "rank": 65, "score": 8.626500129699707}, {"content": "Title: Searching for SARS-COV-2 on Particulate Matter: A Possible Early Indicator of COVID-19 Epidemic Recurrence Content: A number of nations were forced to declare a total shutdown due to COVID-19 infection, as extreme measure to cope with dramatic impact of the pandemic, with remarkable consequences both in terms of negative health outcomes and economic loses. However, in many countries a \"Phase-2\" is approaching and many activities will re-open soon, although with some differences depending on the severity of the outbreak experienced and SARS-COV-2 estimated diffusion in the general population. At the present, possible relapses of the epidemic cannot be excluded until effective vaccines or immunoprophylaxis with human recombinant antibodies will be properly set up and commercialized. COVD-19-related quarantines have triggered serious social challenges, so that decision makers are concerned about the risk of wasting all the sacrifices imposed to the people in these months of quarantine. The availability of possible early predictive indicators of future epidemic relapses would be very useful for public health purposes, and could potentially prevent the suspension of entire national economic systems. On 16 March, a Position Paper launched by the Italian Society of Environmental Medicine (SIMA) hypothesized for the first time a possible link between the dramatic impact of COVID-19 outbreak in Northern Italy and the high concentrations of particulate matter (PM10 and PM2.5) that characterize this area, along with its well-known specific climatic conditions. Thereafter, a survey carried out in the U.S. by the Harvard School of Public Health suggested a strong association between increases in particulate matter concentration and mortality rates due to COVID-19. The presence of SARS-COV-2 RNA on the particulate matter of Bergamo, which is not far from Milan and represents the epicenter of the Italian epidemic, seems to confirm (at least in case of atmospheric stability and high PM concentrations, as it usually occurs in Northern Italy) that the virus can create clusters with the particles and be carried and detected on PM10. Although no assumptions can be made concerning the link between this first experimental finding and COVID-19 outbreak progression or severity, the presence of SARS-COV-2 RNA on PM10 of outdoor air samples in any city of the world could represent a potential early indicator of COVID-19 diffusion. Searching for the viral genome on particulate matter could therefore be explored among the possible strategies for adopting all the necessary preventive measures before future epidemics start.", "qid": 48, "docid": "2mffm988", "rank": 66, "score": 8.621399879455566}, {"content": "Title: Augmenting contact matrices with time-use data for fine-grained intervention modelling of disease dynamics: A modelling analysis Content: Background: Social distancing is an important public health intervention to reduce or interrupt the sustained community transmission of emerging infectious pathogens, such as SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to explore the impact on the epidemic curve of fewer contacts when individuals reduce the time they spend on selected daily activities. Methods: We combined the large-scale empirical data of a social contact survey and a time-use survey to estimate contact matrices by age group (0-15, 16-24, 25-44, 45-64, 65+) and daily activity (work, schooling, transportation, and four leisure activities: social visits, bar/cafe/restaurant visits, park visits, and non-essential shopping). We assumed that reductions in time are proportional to reductions in contacts. The derived matrices were then applied in an age-structured dynamic-transmission model of COVID-19 to explore the effects. Findings: The relative reductions in the derived contact matrices were highest when closing schools (in ages 0-14 years), workplaces (15-64 years), and stopping social visits (65+ years). For COVID-19, the closure of workplaces, schools, and stopping social visits had the largest impact on reducing the epidemic curve and delaying its peak, while the predicted impact of fewer contacts in parks, bars/cafes/restaurants, and non-essential shopping were minimal. Interpretation: We successfully augmented contact matrices with time-use data to predict the highest impact of social distancing measures from reduced contacts when spending less time at work, school, and on social visits. Although the predicted impact from other leisure activities with potential for close physical contact were minimal, changes in mixing patterns and time-use immediately after re-allowing social activities may pose increased short-term transmission risks, especially in potentially crowded environments indoors.", "qid": 48, "docid": "zkjiixuq", "rank": 67, "score": 8.606100082397461}, {"content": "Title: Labs in the time of COVID: an early-career scientist's view Content: The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, cancelation of scientific conferences and delayed experiments have already proven detrimental to the career opportunities of early-career scientists. Moreover, school closures and a lack of systematic support for childcare have been additional challenges for early- and mid-career researchers who have young children. This Editorial describes an early-career researcher's experience and highlights how after efficiently contributing to \u2018flattening the curve\u2019 of COVID-19 infections, the research community has an opportunity for growth and re-structuring.", "qid": 48, "docid": "9eqt5pv5", "rank": 68, "score": 8.604999542236328}, {"content": "Title: Health-education to prevent COVID-19 in schoolchildren: a call to action Content: BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents \u00e2\u0094\u0080 the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices \u00e2\u0094\u0080 hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "qid": 48, "docid": "ccx9klxa", "rank": 69, "score": 8.604998588562012}, {"content": "Title: Health-education to prevent COVID-19 in schoolchildren: a call to action Content: BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents \u2500 the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices \u2500 hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "qid": 48, "docid": "ynaum52m", "rank": 70, "score": 8.604997634887695}, {"content": "Title: Rationing social contact during the COVID-19 pandemic: Transmission risk and social benefits of US locations Content: To prevent the spread of coronavirus disease 2019 (COVID-19), some types of public spaces have been shut down while others remain open. These decisions constitute a judgment about the relative danger and benefits of those locations. Using mobility data from a large sample of smartphones, nationally representative consumer preference surveys, and economic statistics, we measure the relative transmission reduction benefit and social cost of closing 26 categories of US locations. Our categories include types of shops, entertainments, and service providers. We rank categories by their trade-off of social benefits and transmission risk via dominance across 13 dimensions of risk and importance and through composite indexes. We find that, from February to March 2020, there were larger declines in visits to locations that our measures indicate should be closed first.", "qid": 48, "docid": "k408jcow", "rank": 71, "score": 8.587200164794922}, {"content": "Title: The Ethics of Everyday Life in the Midst of a Pandemic. Content: Elderly individuals are at higher risk of serious illness and death if they become infected by the coronavirus. During the current pandemic, my wife and I, at ages seventy-two and seventy-one, respectively, have been paying a person laid off from a job to purchase groceries-a practice that exposes the shopper to risk of infection for our benefit. In this essay, I examine this practice with respect to the normative concepts of treating another person as a means, coercion, exploitation, and complicity.", "qid": 48, "docid": "obe1i6d7", "rank": 72, "score": 8.553099632263184}, {"content": "Title: The Ethics of Everyday Life in the Midst of a Pandemic Content: Elderly individuals are at higher risk of serious illness and death if they become infected by the coronavirus. During the current pandemic, my wife and I, at ages seventy-two and seventy-one, respectively, have been paying a person laid off from a job to purchase groceries-a practice that exposes the shopper to risk of infection for our benefit. In this essay, I examine this practice with respect to the normative concepts of treating another person as a means, coercion, exploitation, and complicity.", "qid": 48, "docid": "xablkr83", "rank": 73, "score": 8.553098678588867}, {"content": "Title: COVID\u201019 Pandemic and Its Impact on the Global Economy: What Does It Take to Turn Crisis into Opportunity? Content: The COVID\u201019 pandemic broke out at a time when there were heightened uncertainties in the global economy. Understanding these uncertainties provides an important background for analyzing the impact of the pandemic on the global economy, assessing the effectiveness of those policy measures in combating the pandemic and reviving the global economy, and predicting the trajectory of the economic recovery in post\u2010pandemic era. We analyze how COVID\u201019 would likely deepen some existing malaise in the global economy, and what could be done to redress these problems while managing economic recovery from the crisis and beyond. We argue that three fundamental factors which could lead to a solid recovery in the post pandemic era are structural reform, new technology and re\u2010integration which could be managed through instituting a new \u201cglobal social contract.\u201d Supported by strong public policies at all levels especially at national levels, the tripartite could serve as salvation of the global economy recovering or re\u2010emerging from this pandemic crisis.", "qid": 48, "docid": "hgsckys9", "rank": 74, "score": 8.53909969329834}, {"content": "Title: Infection prevention guidelines and considerations for paediatric risk groups when reopening primary schools during COVID-19 pandemic, Norway, April 2020 Content: In response to the coronavirus disease (COVID-19) pandemic, most countries implemented school closures. In Norway, schools closed on 13 March 2020. The evidence of effect on disease transmission was limited, while negative consequences were evident. Before reopening, risk-assessment for paediatric risk groups was performed, concluding that most children can attend school with few conditions requiring preventative homeschooling. We here present infection prevention and control guidelines for primary schools and recommendations for paediatric risk groups.", "qid": 48, "docid": "k36e2sob", "rank": 75, "score": 8.529500007629395}, {"content": "Title: COVID 19: Designing and conducting an online mini-multiple interview (MMI) in a dynamic landscape Content: Introduction: The COVID-19 pandemic presented numerous, significant challenges for medical schools, including how to select the best candidates from a pool of applicants when social distancing and other measures prevented \"business as usual\" admissions processes. However, selection into medical school is the gateway to medicine in many countries, and it is critical to use processes which are evidence-based, valid and reliable even under challenging circumstances. Our challenge was to plan and conduct a multiple-mini interview (MMI) in a dynamic and stringent safe distancing context.Methods: This paper reports a case study of how to plan, re-plan and conduct MMIs in an environment where substantially tighter safe distancing measures were introduced just before the MMI was due to be delivered.Results: We report on how to design and implement a fully remote, online MMI which ensured the safety of candidates and assessors.Discussion: We discuss the challenges of this approach and also reflect on broader issues associated with selection into medical school during a pandemic. The aim of the paper is to provide broadly generalizable guidance to other medical schools faced with the challenge of selecting future students under difficult conditions.", "qid": 48, "docid": "4tczn96x", "rank": 76, "score": 8.527099609375}, {"content": "Title: COVID 19: Designing and conducting an online mini-multiple interview (MMI) in a dynamic landscape. Content: Introduction: The COVID-19 pandemic presented numerous, significant challenges for medical schools, including how to select the best candidates from a pool of applicants when social distancing and other measures prevented \"business as usual\" admissions processes. However, selection into medical school is the gateway to medicine in many countries, and it is critical to use processes which are evidence-based, valid and reliable even under challenging circumstances. Our challenge was to plan and conduct a multiple-mini interview (MMI) in a dynamic and stringent safe distancing context.Methods: This paper reports a case study of how to plan, re-plan and conduct MMIs in an environment where substantially tighter safe distancing measures were introduced just before the MMI was due to be delivered.Results: We report on how to design and implement a fully remote, online MMI which ensured the safety of candidates and assessors.Discussion: We discuss the challenges of this approach and also reflect on broader issues associated with selection into medical school during a pandemic. The aim of the paper is to provide broadly generalizable guidance to other medical schools faced with the challenge of selecting future students under difficult conditions.", "qid": 48, "docid": "l0n9gjhd", "rank": 77, "score": 8.527098655700684}, {"content": "Title: What Is the Appropriate Use of Laparoscopy over Open Procedures in the Current COVID-19 Climate? Content: INTRODUCTION: Among surgeons worldwide, a concern with the use of minimally invasive techniques has been raised due to a proposed risk of viral transmission of the coronavirus disease of 2019 (COVID-19) with the creation of pneumoperitoneum. Due to this proposed concern, we sought to collect the available data and evaluate the use of laparoscopy and the risk of COVID-19 transmission. METHODS: A literature review of viral transmission in surgery and of the available literature regarding the transmission of the COVID-19 virus was performed. We additionally reviewed surgical society guidelines and recommendations regarding surgery during this pandemic. RESULTS: Few studies have been performed on viral transmission during surgery, but to date there is no study that demonstrates or can suggest the ability for a virus to be transmitted during surgical treatment whether open or laparoscopic. There is no societal consensus on limiting or restricting laparoscopic or robotic surgery; however, there is expert consensus on the modification of standard practices to minimize any risk of transmission. CONCLUSIONS: Despite very little evidence to support viral transmission through laparoscopic or open approaches, we recommend making modifications to surgical practice such as the use of smoke evacuation and minimizing energy device use among other measures to minimize operative staff exposure to aerosolized particles.", "qid": 48, "docid": "cafoic4y", "rank": 78, "score": 8.525099754333496}, {"content": "Title: Modelling the impact of reducing control measures on the COVID-19 pandemic in a low transmission setting Content: Aims: We assessed COVID-19 epidemic risks associated with relaxing a set of physical distancing restrictions in the state of Victoria, Australia - a setting with low community transmission - in line with a national framework that aims to balance sequential policy relaxations with longer-term public health and economic need. Methods: An agent-based model, Covasim, was calibrated to the local COVID-19 epidemiological and policy environment. Contact networks were modelled to capture transmission risks in households, schools and workplaces, and a variety of community spaces (e.g. public transport, parks, bars, cafes/restaurants) and activities (e.g. community or professional sports, large events). Policy changes that could prevent or reduce transmission in specific locations (e.g. opening/closing businesses) were modelled in the context of interventions that included testing, contact tracing (including via a smartphone app), and quarantine. Results: Policy changes leading to the gathering of large, unstructured groups with unknown individuals (e.g. bars opening, increased public transport use) posed the greatest risk, while policy changes leading to smaller, structured gatherings with known individuals (e.g. small social gatherings) posed least risk. In the model, epidemic impact following some policy changes took more than two months to occur. Model outcomes support continuation of working from home policies to reduce public transport use, and risk mitigation strategies in the context of social venues opening, such as >30% population-uptake of a contact-tracing app, physical distancing policies within venues reducing transmissibility by >40%, or patron identification records being kept to enable >60% contact tracing. Conclusions: In a low transmission setting, care should be taken to avoid lifting sequential COVID-19 policy restrictions within short time periods, as it could take more than two months to detect the consequences of any changes. These findings have implications for other settings with low community transmission where governments are beginning to lift restrictions.", "qid": 48, "docid": "9iaiiqqi", "rank": 79, "score": 8.521100044250488}, {"content": "Title: On pandemics and the duty to care: whose duty? who cares? Content: BACKGROUND: As a number of commentators have noted, SARS exposed the vulnerabilities of our health care systems and governance structures. Health care professionals (HCPs) and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis. Indeed, HCPs \u2013 both in clinical care and in public health \u2013 were severely tested by SARS. Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried. Many were exposed to serious risk of morbidity and mortality, as evidenced by the World Health Organization figures showing that approximately 30% of reported cases were among HCPs, some of whom died from the infection. Despite this challenge, professional codes of ethics are silent on the issue of duty to care during communicable disease outbreaks, thus providing no guidance on what is expected of HCPs or how they ought to approach their duty to care in the face of risk. DISCUSSION: In the aftermath of SARS and with the spectre of a pandemic avian influenza, it is imperative that we (re)consider the obligations of HCPs for patients with severe infectious diseases, particularly diseases that pose risks to those providing care. It is of pressing importance that organizations representing HCPs give clear indication of what standard of care is expected of their members in the event of a pandemic. In this paper, we address the issue of special obligations of HCPs during an infectious disease outbreak. We argue that there is a pressing need to clarify the rights and responsibilities of HCPs in the current context of pandemic flu preparedness, and that these rights and responsibilities ought to be codified in professional codes of ethics. Finally, we present a brief historical accounting of the treatment of the duty to care in professional health care codes of ethics. SUMMARY: An honest and critical examination of the role of HCPs during communicable disease outbreaks is needed in order to provide guidelines regarding professional rights and responsibilities, as well as ethical duties and obligations. With this paper, we hope to open the social dialogue and advance the public debate on this increasingly urgent issue.", "qid": 48, "docid": "58czem0j", "rank": 80, "score": 8.510700225830078}, {"content": "Title: Multisystem Resilience for Children and Youth in Disaster: Reflections in the Context of COVID-19 Content: In the context of rising disasters worldwide and the challenges of the COVID-19 pandemic, this commentary considers the implications of findings in resilience science on children and youth for disaster preparation and response. The multisystem challenges posed by disasters are illustrated by the COVID-19 pandemic. We discuss the significance of disasters in the history of resilience science and the emergence of a unifying systems definition of resilience. Principles of a multisystem perspective on resilience and major findings on what matters for young people in disasters are delineated with reference to the pandemic. Striking parallels are noted in the psychosocial resilience factors identified at the level of individual children, families, schools, and communities. These parallels suggest that adaptive capacities associated with resilience in these interacting systems reflect interconnected networks and processes that co-evolved and may operate in concert. As resilience science moves toward integrated theory, knowledge, and applications in practice, particularly in disaster risk reduction and resilience promotion, more focus will be needed on multisystem and multidisciplinary research, communication, training, and planning.", "qid": 48, "docid": "6pqtr68q", "rank": 81, "score": 8.501700401306152}, {"content": "Title: COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use Content: OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.", "qid": 48, "docid": "i44s4vqr", "rank": 82, "score": 8.493599891662598}, {"content": "Title: COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use. Content: OBJECTIVE To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS A detailed search of the scientific and popular literature was performed. RESULTS There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.", "qid": 48, "docid": "oooat8xj", "rank": 83, "score": 8.493598937988281}, {"content": "Title: Lopinavir-Ritonavir in treatment of COVID-19: A dynamic systematic benefit-risk assessment Content: Background: COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required due to the urgent unmet public need. Importantly it allows additional data to be incorporated as it becomes available, and re-evaluation of the benefit-risk profile. Methods: A systematic benefit-risk assessment was conducted using the Benefit-Risk Action team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and EmBase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance. Results: In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (HR=1.31, 95% CI:0.95, 1.80). There appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). In particular, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared to standard of care (13% vs 27%). Limited data were available for comparison of lopinavir-ritonavir to other treatments. Conclusions: Based on currently available data, there was no clear benefit for use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events, including acute respiratory distress syndrome. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.", "qid": 48, "docid": "8v2rpcjd", "rank": 84, "score": 8.479700088500977}, {"content": "Title: Searching for SARS-COV-2 on Particulate Matter: A Possible Early Indicator of COVID-19 Epidemic Recurrence Content: A number of nations were forced to declare a total shutdown due to COVID-19 infection, as extreme measure to cope with dramatic impact of the pandemic, with remarkable consequences both in terms of negative health outcomes and economic loses. However, in many countries a \u201cPhase-2\u201d is approaching and many activities will re-open soon, although with some differences depending on the severity of the outbreak experienced and SARS-COV-2 estimated diffusion in the general population. At the present, possible relapses of the epidemic cannot be excluded until effective vaccines or immunoprophylaxis with human recombinant antibodies will be properly set up and commercialized. COVD-19-related quarantines have triggered serious social challenges, so that decision makers are concerned about the risk of wasting all the sacrifices imposed to the people in these months of quarantine. The availability of possible early predictive indicators of future epidemic relapses would be very useful for public health purposes, and could potentially prevent the suspension of entire national economic systems. On 16 March, a Position Paper launched by the Italian Society of Environmental Medicine (SIMA) hypothesized for the first time a possible link between the dramatic impact of COVID-19 outbreak in Northern Italy and the high concentrations of particulate matter (PM(10) and PM(2.5)) that characterize this area, along with its well-known specific climatic conditions. Thereafter, a survey carried out in the U.S. by the Harvard School of Public Health suggested a strong association between increases in particulate matter concentration and mortality rates due to COVID-19. The presence of SARS-COV-2 RNA on the particulate matter of Bergamo, which is not far from Milan and represents the epicenter of the Italian epidemic, seems to confirm (at least in case of atmospheric stability and high PM concentrations, as it usually occurs in Northern Italy) that the virus can create clusters with the particles and be carried and detected on PM(10). Although no assumptions can be made concerning the link between this first experimental finding and COVID-19 outbreak progression or severity, the presence of SARS-COV-2 RNA on PM(10) of outdoor air samples in any city of the world could represent a potential early indicator of COVID-19 diffusion. Searching for the viral genome on particulate matter could therefore be explored among the possible strategies for adopting all the necessary preventive measures before future epidemics start.", "qid": 48, "docid": "mlmglk8v", "rank": 85, "score": 8.473600387573242}, {"content": "Title: Increased stressful impact among general population in mainland China amid the COVID-19 pandemic: A nationwide cross-sectional study conducted after Wuhan city's travel ban was lifted. Content: OBJECTIVES Our study aimed to determine the impact of the COVID-19 pandemic on psychological responses and lifestyle changes among the general population in mainland China following the re-opening of the Wuhan city. METHODS A cross-sectional survey was conducted in April 2020. Participants of Chinese nationality aged \u2a7e 18 years were asked to complete a modified validated Chinese version of a questionnaire regarding the impact of event scale (IES), family and social support, mental health-related lifestyle changes, and indicators of negative mental health impacts. RESULTS A total of 728 participants (i.e., 217 males and 511 females) completed the questionnaire. The mean age of the participants was 32.9 \u00b1 10.4 years, with a majority of them (92.2%) having a higher educational qualification level. The overall mean IES in participants was 21.5 \u00b1 7.0, reflecting mild stressful impact (i.e., following the re-opening of the Wuhan city); 25.5% of the participants had an IES score \u2a7e 26. Being females and married were significantly associated with a higher mean IES score. The overall mean scores for intrusion and avoidance score scales in participants were 9.4 \u00b1 3.7 and 12.1 \u00b1 4.2, respectively. CONCLUSIONS The COVID-19 pandemic was associated with increased stressful impact in our participants following the re-opening of the Wuhan city when compared with our previous study, which should not be taken lightly.", "qid": 48, "docid": "ghrgj3e5", "rank": 86, "score": 8.465200424194336}, {"content": "Title: The work of culture and C-19 Content: This article offers some initial commentary on the cultural impacts of COVID-19. It first considers how the pandemic might already have shifted the focus - or challenged our capacities - for cultural studies scholarship. However, the article is more centrally concerned with how measures designed to combat COVID-19 have begun to transform patterns of cultural consumption, production and work. The article considers the current status of cultural workers, in the midst of (yet further) crisis, and poses questions of what might culture be or become, in and beyond the current state of emergency.", "qid": 48, "docid": "ttzij9mk", "rank": 87, "score": 8.464300155639648}, {"content": "Title: Accelerated Graduation and the Deployment of New Physicians During the COVID-19 Pandemic Content: The COVID-19 pandemic has presented unprecedented challenges and opportunities for medical schools in the United States. In this Invited Commentary, the authors describe a unique collaboration between the University of Massachusetts Medical School (UMMS), the only public medical school in the state; the University of Massachusetts Memorial Medical Center (UMMMC); and the Commonwealth of Massachusetts. Through this partnership, UMMS was able to graduate fourth-year medical students 2 months early and deploy them to UMMMC to care for patients and alleviate workforce shortages during the COVID-19 surge, which peaked in Massachusetts in April 2020. The authors describe how they determined if students had fulfilled graduation requirements to graduate early, what commencement and the accompanying awards ceremony looked like this year as virtual events, the special emergency 90-day limited license these new graduates were given to practice at UMMMC during this time, and the impact these new physicians had in the hospital allowing residents and attendings to be redeployed to care for COVID-19 patients.", "qid": 48, "docid": "wpay4ffo", "rank": 88, "score": 8.449199676513672}, {"content": "Title: The COVID\u201019 epidemic of manuscripts Content: In the midst of the novel coronavirus pandemic\u2014referred to as COVID\u201019\u2014there has been much uncertainty. We remain uncertain about its precise origin, its structure and composition, how best to test for it, or for resulting immunity, whether or not exposure leads to immunity, whether or not disposable surgical masks are effective, why men and some ethnic minorities are more susceptible and just exactly what the death rate as a result of this virus is. However, one thing is absolutely clear, there has been an epidemic of manuscripts on the subject of COVID\u201019 to nursing journals and, amongst these new manuscripts the rejection rate is, unfortunately, very high.", "qid": 48, "docid": "5d7zien3", "rank": 89, "score": 8.438699722290039}, {"content": "Title: Medical Student Mobilization During A Crisis: Lessons From A COVID-19 Medical Student Response Team Content: PROBLEM: On March 17, 2020, the Association of American Medical Colleges recommended the suspension of all direct patient contact responsibilities for medical students because of the COVID-19 pandemic. Given this change, medical students nationwide had to grapple with how and where they could fill the evolving needs of their schools' affiliated clinical sites, physicians, and patients and the community. APPROACH: At Harvard Medical School (HMS), student leaders created a COVID-19 Medical Student Response Team to: (1) develop a student-led organizational structure that would optimize students' ability to efficiently mobilize interested peers in the COVID-19 response, both clinically and in the community, in a strategic, safe, smart, and resource-conscious way; and (2) serve as a liaison with the administration and hospital leaders to identify evolving needs and rapidly engage students in those efforts. OUTCOMES: Within a week of its inception, the COVID-19 Medical Student Response Team had more than 500 medical student volunteers from HMS and had shared the organizational framework of the response team with multiple medical schools across the country. The HMS student volunteers joined any of the 4 virtual committees to complete this work: Education for the Medical Community, Education for the Broader Community, Activism for Clinical Support, and Community Activism. NEXT STEPS: The COVID-19 Medical Student Response Team helped to quickly mobilize hundreds of students and has been integrated into HMS's daily workflow. It may serve as a useful model for other schools and hospitals seeking medical student assistance during the COVID-19 pandemic. Next steps include expanding the initiative further, working with the leaders of response teams at other medical schools to coordinate efforts, and identifying new areas of need at local hospitals and within nearby communities that might benefit from medical student involvement as the pandemic evolves.", "qid": 48, "docid": "xpou33e6", "rank": 90, "score": 8.419500350952148}, {"content": "Title: Medical Student Mobilization During a Crisis: Lessons From a COVID-19 Medical Student Response Team Content: On March 17, 2020, the Association of American Medical Colleges recommended the suspension of all direct patient contact responsibilities for medical students because of the COVID-19 pandemic. Given this change, medical students nationwide had to grapple with how and where they could fill the evolving needs of their schools\u2019 affiliated clinical sites, physicians, and patients and the community. APPROACH: At Harvard Medical School (HMS), student leaders created a COVID-19 Medical Student Response Team to: (1) develop a student-led organizational structure that would optimize students\u2019 ability to efficiently mobilize interested peers in the COVID-19 response, both clinically and in the community, in a strategic, safe, smart, and resource-conscious way; and (2) serve as a liaison with the administration and hospital leaders to identify evolving needs and rapidly engage students in those efforts. OUTCOMES: Within a week of its inception, the COVID-19 Medical Student Response Team had more than 500 medical student volunteers from HMS and had shared the organizational framework of the response team with multiple medical schools across the country. The HMS student volunteers joined any of the 4 virtual committees to complete this work: Education for the Medical Community, Education for the Broader Community, Activism for Clinical Support, and Community Activism. NEXT STEPS: The COVID-19 Medical Student Response Team helped to quickly mobilize hundreds of students and has been integrated into HMS\u2019s daily workflow. It may serve as a useful model for other schools and hospitals seeking medical student assistance during the COVID-19 pandemic. Next steps include expanding the initiative further, working with the leaders of response teams at other medical schools to coordinate efforts, and identifying new areas of need at local hospitals and within nearby communities that might benefit from medical student involvement as the pandemic evolves.", "qid": 48, "docid": "ys68z5vx", "rank": 91, "score": 8.419499397277832}, {"content": "Title: COVID-19: ensuring our medical equipment can meet the challenge Content: To predict the spread of coronavirus disease globally and consequently prepare the hospital facilities with the required technology is a challenge. The availability of essential medical equipment to support patients affected by Covid-19 is globally limited. Areas covered This perspective gives a technical view of the pandemic focusing on the main actions taken by regulatory agencies to cope with the shortage of devices. The risk/benefit assessment and the main infection control policies in the clinical practices are also looked at. Expert opinion Regulatory agencies have amended their medical devices directives to address the pandemic, but each in a different way. In this exceptional situation scientist and technology experts in collaboration with medical specialists should work together to re-assess the risk analysis on medical equipment management and their use and re-use in this context with the aim to improve global health care Every effort must be made to provide the necessary devices at least with the minimum acceptable performances for Covid-19 patients while maintaining a high standard of safety for users. The aim of the present manuscript is to highlight the technical challenges in order to prevent, through targeted actions, operating standards from falling below the standards of care due to a lack of medical devices. Abbreviations AKI: acute Kidney Injury; ARGMD: Australian Regulatory Guidelines for Medical Devices; Covid-19: Coronavirus disease; FDA: Food and Drug Administration; ECMO: Extracorporeal Membrane Oxygenation; EU: European Union; ICU: Intensive Care Unit; WHO: World Health Organization; MHRA: Medicines and Healthcare products Regulatory Agency; MDR: Medical Device Regulation; SARI: Severe Acute Respiratory Infection.", "qid": 48, "docid": "5wosung0", "rank": 92, "score": 8.41469955444336}, {"content": "Title: COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments Content: Scientists hypothesized that drugs such as ibuprofen or renin-angiotensin system (RAS) blockers could exacerbate the novel coronavirus disease COVID-19 by upregulating the angiotensin-converting enzyme 2 (ACE2), which serves as an entry receptor for the coronavirus SARS-CoV-2. This hypothesis was taken up by the lay press and led to concerns among doctors and patients whether the use of these drugs was still safe and justified against the background of the pandemic spread of SARS-CoV-2 with an increasing number of cases and deaths. In this article, we summarize what is known about the effect of RAS blockers or non-steroidal anti-inflammatory drugs (NSAIDs) on the course of COVID-19 disease. In the case of RAS inhibition, we also find evidence for the opposite hypothesis, namely, that RAS inhibition in COVID-19 could be protective. In view of the inconsistent and limited evidence and after weighing up the benefits and risks, we would not currently recommend discontinuing or switching an effective treatment with RAS blockers. NSAIDs should be used at the lowest effective dose for the shortest possible period. The choice of drug to treat COVID-19-associated fever or pain should be based on a benefit-risk assessment for known side effects (e.g., kidney damage, gastrointestinal ulceration).", "qid": 48, "docid": "s8b4j0j2", "rank": 93, "score": 8.392399787902832}, {"content": "Title: Just the facts: What drugs are safe and effective for COVID-19? Content: A 53-year-old male presents with cough, fever, and myalgias for 7 days. Vitals include temperature, 38.0\u00b0C; heart rate, 110; blood pressure, 118/70 mm Hg; respiration rate, 28; and oxygen saturation 83% on room air. His only past medical history is hypertension. Your community is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. The patient is hypoxic but responds to oxygen supplementation with nasal cannula and a face mask. His chest x-ray demonstrates multifocal infiltrates. Are there any therapeutic agents currently available for COVID-19?", "qid": 48, "docid": "h76dfo1j", "rank": 94, "score": 8.388199806213379}, {"content": "Title: Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment Content: INTRODUCTION AND OBJECTIVE: COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for the use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required because of the urgent unmet public need. Importantly, it allows additional data to be incorporated as they become available, and re-evaluation of the benefit-risk profile. METHODS: A systematic benefit-risk assessment was conducted using the Benefit-Risk Action Team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in severe COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and Embase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance. RESULTS: We screened 143 papers from PubMed and 264 papers from Embase for lopinavir-ritonavir; seven papers were included in the final benefit-risk assessment. In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (hazard ratio 1.31, 95% confidence interval 0.95\u20131.80). From one study, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard of care (13% vs 27%). There also appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). Limited data were available for comparison of lopinavir-ritonavir to other treatments. CONCLUSIONS: Based on currently available data, there was no clear benefit for the use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events. There was a reduction in acute respiratory distress syndrome with lopinavir-ritonavir in one study. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.", "qid": 48, "docid": "3qruat3s", "rank": 95, "score": 8.38759994506836}, {"content": "Title: Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment Content: INTRODUCTION AND OBJECTIVE: COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for the use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required because of the urgent unmet public need. Importantly, it allows additional data to be incorporated as they become available, and re-evaluation of the benefit-risk profile. METHODS: A systematic benefit-risk assessment was conducted using the Benefit-Risk Action Team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in severe COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and Embase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance. RESULTS: We screened 143 papers from PubMed and 264 papers from Embase for lopinavir-ritonavir; seven papers were included in the final benefit-risk assessment. In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (hazard ratio 1.31, 95% confidence interval 0.95-1.80). From one study, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard of care (13% vs 27%). There also appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). Limited data were available for comparison of lopinavir-ritonavir to other treatments. CONCLUSIONS: Based on currently available data, there was no clear benefit for the use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events. There was a reduction in acute respiratory distress syndrome with lopinavir-ritonavir in one study. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.", "qid": 48, "docid": "jv8vu2tp", "rank": 96, "score": 8.387598991394043}, {"content": "Title: Re-Opening Schools Safely: The Case for Collaboration, Constructive Disruption of Pre-COVID Expectations, and Creative Solutions Content:", "qid": 48, "docid": "101aqyd5", "rank": 97, "score": 8.384400367736816}, {"content": "Title: Appr\u00e9hender le COVID-19 au fil de l\u2019eau en tant que psychiatre d\u2019enfant et d\u2019adolescent Content: R\u00e9sum\u00e9 Le COVID-19 est une maladie multi-organes li\u00e9e \u00e0 une infection par le virus SARS-CoV2 qui est devenue une pand\u00e9mie au d\u00e9but de l\u2019ann\u00e9e 2020. Difficile de d\u00e9crire autrement qu\u2019en t\u00e9moignant \u00e0 chaud ce que cette pand\u00e9mie implique pour un psychiatre d\u2019enfants. Je propose de parcourir les principales questions \u00e9thiques qui se sont pos\u00e9es; de d\u00e9crire comment mon \u00e9quipe hospitali\u00e8re s\u2019est r\u00e9organis\u00e9e pour faire face aux nouvelles demandes et questionnements, en particulier en ouvrant une unit\u00e9 d\u00e9di\u00e9e aux personnes avec autisme et comportements d\u00e9fis atteints par le COVID-19; et d\u2019aborder, dans un contexte de discussion nationale, comment la discipline a cherch\u00e9 \u00e0 comprendre les conditions d\u2019un certain bien-\u00eatre pendant le confinement. Enfin, j\u2019essaierai de terminer par des r\u00e9flexions plus sp\u00e9culatives concernant le d\u00e9confinement. Abstract COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.", "qid": 48, "docid": "lmo0ry4k", "rank": 98, "score": 8.371899604797363}, {"content": "Title: Consequences of physical distancing emanating from the COVID-19 pandemic: An australian perspective Content: The sobering reality of the COVID-19 pandemic is that it has brought people together at home at a time when we want them apart in the community. This will bring both benefits and challenges. It will affect people differently based upon their age, health status, resilience, family support structures, and socio-economic background. This article will assess the impact in high income countries like Australia, where the initial wave of infection placed the elderly at the greatest risk of death whilst the protective measures of physical distancing, self-isolation, increased awareness of hygiene practices, and school closures with distance learning has had considerable impact on children and families acutely and may have ramifications for years to come.", "qid": 48, "docid": "9d7vxjys", "rank": 99, "score": 8.369999885559082}, {"content": "Title: Increased stressful impact among general population in mainland China amid the COVID-19 pandemic: A nationwide cross-sectional study conducted after Wuhan city's travel ban was lifted Content: OBJECTIVES: Our study aimed to determine the impact of the COVID-19 pandemic on psychological responses and lifestyle changes among the general population in mainland China following the re-opening of the Wuhan city. METHODS: A cross-sectional survey was conducted in April 2020. Participants of Chinese nationality aged \u00e2\u00a9\u00be 18 years were asked to complete a modified validated Chinese version of a questionnaire regarding the impact of event scale (IES), family and social support, mental health-related lifestyle changes, and indicators of negative mental health impacts. RESULTS: A total of 728 participants (i.e., 217 males and 511 females) completed the questionnaire. The mean age of the participants was 32.9 \u00b1 10.4 years, with a majority of them (92.2%) having a higher educational qualification level. The overall mean IES in participants was 21.5 \u00b1 7.0, reflecting mild stressful impact (i.e., following the re-opening of the Wuhan city); 25.5% of the participants had an IES score \u00e2\u00a9\u00be 26. Being females and married were significantly associated with a higher mean IES score. The overall mean scores for intrusion and avoidance score scales in participants were 9.4 \u00b1 3.7 and 12.1 \u00b1 4.2, respectively. CONCLUSIONS: The COVID-19 pandemic was associated with increased stressful impact in our participants following the re-opening of the Wuhan city when compared with our previous study, which should not be taken lightly.", "qid": 48, "docid": "93pm0p4w", "rank": 100, "score": 8.366999626159668}]}
{"query": "do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection?", "hits": [{"content": "Title: Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2 Content: The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "qid": 49, "docid": "dptgg05n", "rank": 1, "score": 22.31999969482422}, {"content": "Title: T-cell-mediated immune response to respiratory coronaviruses Content: Emerging respiratory coronaviruses such as the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV) pose potential biological threats to humans. SARS and MERS are manifested as severe atypical pneumonia associated with high morbidity and mortality in humans. The majority of studies carried out in SARS-CoV-infected humans and animals attribute a dysregulated/exuberant innate response as a leading contributor to SARS-CoV-mediated pathology. A decade after the 2002\u20132003 SARS epidemic, we do not have any approved preventive or therapeutic agents available in case of re-emergence of SARS-CoV or other related viruses. A strong neutralizing antibody response generated against the spike (S) glycoprotein of SARS-CoV is completely protective in the susceptible host. However, neutralizing antibody titers and the memory B cell response are short-lived in SARS-recovered patients and the antibody will target primary homologous strain. Interestingly, the acute phase of SARS in humans is associated with a severe reduction in the number of T cells in the blood. Surprisingly, only a limited number of studies have explored the role of the T cell-mediated adaptive immune response in respiratory coronavirus pathogenesis. In this review, we discuss the role of anti-virus CD4 and CD8 T cells during respiratory coronavirus infections with a special emphasis on emerging coronaviruses.", "qid": 49, "docid": "nj1p4ehx", "rank": 2, "score": 22.131900787353516}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic Content: BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 49, "docid": "j67b1leq", "rank": 3, "score": 21.374099731445312}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic. Content: BACKGROUND: : SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: : To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: : Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm appears to contribute to the damage in ARDS. IMPLICATIONS: : In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 49, "docid": "mpf6lxxr", "rank": 4, "score": 21.37409782409668}, {"content": "Title: Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19 Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1\u20133, most targeting the viral \u2018spike\u2019 glycoprotein (S) S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4\u20136 Eliciting neutralizing antibodies that block S\u2013ACE2 interaction7\u20139, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11 However, although prototypic S-based vaccines show promise in animal models12\u201314, the immunogenic properties of S in humans are poorly resolved In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19) We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes", "qid": 49, "docid": "5czqzmvj", "rank": 5, "score": 21.13680076599121}, {"content": "Title: Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. Content: UNLABELLED Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-\u03b3], tumor necrosis factor alpha [TNF-\u03b1], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection. IMPORTANCE Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.", "qid": 49, "docid": "iub5hvz9", "rank": 6, "score": 20.974000930786133}, {"content": "Title: Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study. Content: RATIONALE A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.", "qid": 49, "docid": "mtm5xocw", "rank": 7, "score": 20.149900436401367}, {"content": "Title: Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion Content: Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus", "qid": 49, "docid": "eml8uilb", "rank": 8, "score": 19.801599502563477}, {"content": "Title: Immune responses to porcine epidemic diarrhea virus (PEDV) in swine and protection against subsequent infection Content: Understanding the immune responses against Porcine epidemic diarrhea virus (PEDV) is important to prevent infection and to design control strategies. We evaluated both systemic and mucosal immune responses to PEDV in pigs and assessed if prior exposure to virus protects against re-infection. Three-week-old pigs were infected with PEDV and immune response in blood, intestine, and mesenteric lymph node (MLN) was evaluated. At 30 dpi, virus exposed pigs were challenged with a field isolate of PEDV and immune response at 5 d post challenge was evaluated. We found that PEDV RNA persists in the intestine even after fecal shedding of the virus was stopped at 28 dpi and pigs previously exposed to PEDV are protected from virus shedding after re-infection. PEDV infection induced both humoral and cell mediated immune response with an increase in PEDV specific IgA and IgG antibodies in intestine and serum. Flow cytometry analysis showed a significantly higher frequency of B cells and lower frequency of T cells at 4 dpi. The frequency of CD4/CD8 double positive (DP) memory T cells was significantly increased in the MLN of challenged animals. These studies may provide further insights into understanding the mucosal immune response to PEDV and its role in protection against disease.", "qid": 49, "docid": "txdawva5", "rank": 9, "score": 19.703699111938477}, {"content": "Title: Generation of protective pneumococcal-specific nasal resident memory CD4(+) T cells via parenteral immunization Content: The generation of tissue-resident memory T cells (T(RM)) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of T(RM) is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4(+) T cells can provide capsular antibody-independent protection against nasal carriage of Streptococcus pneumoniae; but whether pneumococcus-responsive T(RM) are localized within the nasal mucosa and are sufficient for protection from carriage has not been determined. Here we show that intranasal administration of live or killed pneumococci to mice generates pneumococcus-responsive IL-17A-producing CD4(+) mucosal T(RM). Furthermore, we show that these cells are sufficient to mediate long-lived, neutrophil-dependent protection against subsequent pneumococcal nasal challenge. Unexpectedly, and in contrast with the prevailing paradigm, we found that parenteral administration of killed pneumococci also generates protective IL-17A(+)CD4(+) T(RM) in the nasal mucosa. These results demonstrate a critical and sufficient role of T(RM) in prevention of pneumococcal colonization, and further that these cells can be generated by parenteral immunization. Our findings therefore have important implications regarding the generation of immune protection at mucosal surfaces by vaccination.", "qid": 49, "docid": "dxdr6oan", "rank": 10, "score": 19.508499145507812}, {"content": "Title: Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection Content: SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-\u03b3 was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8(+) T cells produced IFN-\u03b3, whereas memory CD4(+) T cells produced IFN-\u03b3, IL-2 or TNF-\u03b1. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.", "qid": 49, "docid": "anaqgzvi", "rank": 11, "score": 19.292800903320312}, {"content": "Title: COVID-19 and the immune system. Content: A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease. While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression. Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease. Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections. In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3. Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role. Specific IgA response appears to be stronger and more persistent than IgM response. Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease.", "qid": 49, "docid": "2o3dvi2d", "rank": 12, "score": 19.210599899291992}, {"content": "Title: COVID-19 and the immune system Content: A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3 Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role Specific IgA response appears to be stronger and more persistent than IgM response Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease", "qid": 49, "docid": "p6h7k7ty", "rank": 13, "score": 19.21059799194336}, {"content": "Title: VCAM-1/\u03b14\u03b21 integrin interaction is crucial for prompt recruitment of immune T cells into the brain during the early stage of reactivation of chronic infection with Toxoplasma gondii to prevent toxoplasmic encephalitis. Content: Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/\u03b14\u03b21 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-\u03b14 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3\u03b4, CD4, CD8\u03b2, gamma interferon (IFN-\u03b3), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4(+) and CD8(+) T cells in the brain were significantly less in mice treated with anti-\u03b14 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-\u03b14 integrin antibody-treated than in control antibody-treated animals, even though IFN-\u03b3 and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/\u03b14\u03b21 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-\u03b3-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth.", "qid": 49, "docid": "ubnzkfwz", "rank": 14, "score": 19.09119987487793}, {"content": "Title: Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: A need for early immune-modulators for severe cases Content: It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of \u2018protein homeostasis system\u2019; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia.", "qid": 49, "docid": "4q6d048r", "rank": 15, "score": 19.073400497436523}, {"content": "Title: Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection Content: Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-\u03b3 following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-\u03b3 in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.", "qid": 49, "docid": "t0ij21io", "rank": 16, "score": 18.998199462890625}, {"content": "Title: The immune response to influenza in older humans: beyond immune senescence Content: Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cell-mediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (\u22652) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro- and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.", "qid": 49, "docid": "6nsuttwt", "rank": 17, "score": 18.858600616455078}, {"content": "Title: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus Content: Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.", "qid": 49, "docid": "itu39mln", "rank": 18, "score": 18.74959945678711}, {"content": "Title: Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS Content: The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID-19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID-19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID-19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T-cell response against SARS-CoV-2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID-19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID-19, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "qid": 49, "docid": "3nnlkbph", "rank": 19, "score": 18.726200103759766}, {"content": "Title: Immune responses and pathogenesis of SARS\u2010CoV\u20102 during an outbreak in Iran: Comparison with SARS and MERS Content: The beginning of 2020 has seen the emergence of COVID\u201019, an outbreak caused by a novel coronavirus, SARS\u2010CoV\u20102, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID\u201019 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID\u201019 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID\u201019 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T\u2010cell response against SARS\u2010CoV\u20102 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID\u201019 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID\u201019, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "qid": 49, "docid": "vpomgedg", "rank": 20, "score": 18.726198196411133}, {"content": "Title: T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. Content: The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-gamma) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-gamma-secreting T-cell response in HLA-A2(+) donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2(+) healthy donors or in HLA-A2(-) donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2(+) SARS-CoV-infected patients.", "qid": 49, "docid": "88fv2ea4", "rank": 21, "score": 18.553499221801758}, {"content": "Title: Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 Content: Background: SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the pathogenesis and outcome of COVID-19. We aimed to investigate which specific responses from either cellular or humoral immunity associate to severity and progression of COVID-19. Methods: A cohort of 276 patients classified in mild, moderate and severe, was studied. Peripheral blood lymphocyte subpopulations were quantified by flow cytometry, and immunoglobulins and complement proteins by nephelometry. Results: At admission, dramatic lymphopenia of T, B and NK cells associated to severity. However, only the proportion of B cells increased, while T and NK cells appeared unaffected. Accordingly, the number of plasma cells and circulating follicular helper T cells (cTfh) increased, but levels of IgM, IgA and IgG were unaffected. When degrees of severity were considered, IgG was lower in severe patients, suggesting an IgG consumption by complement activation or antibody-dependent cellular cytotoxicity (ADCC). Activated CD56-CD16+ NK-cells, which mediate ADCC, were increased. Regarding complement, C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, compared to healthy donors. Moreover, IgG and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Conclusion: Our study provides important clues to understand the immune response observed in COVID-19 patients, which is probably related to viral clearance, but also underlies its pathogenesis and severity. This study associates for the first time COVID-19 severity with an imbalanced humoral immune response characterized by excessive consumption of IgG and C4, identifying new targets for therapeutic intervention.", "qid": 49, "docid": "7oaxtrul", "rank": 22, "score": 18.512500762939453}, {"content": "Title: Comparative evaluation of two hemagglutinating encephalomyelitis coronavirus vaccine candidates in mice. Content: Porcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-\u03b3). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.", "qid": 49, "docid": "33y3qf20", "rank": 23, "score": 18.4822998046875}, {"content": "Title: Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus Content: Abstract While the 2002\u20132003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4+ T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV.", "qid": 49, "docid": "52vzwax8", "rank": 24, "score": 18.419200897216797}, {"content": "Title: Rapid expansion of CD8+ T cells in wild-type and type I interferon receptor-deficient mice correlates with protection after low-dose emergency immunization with modified vaccinia virus Ankara. Content: UNLABELLED Immunization with modified vaccinia virus Ankara (MVA) can rapidly protect mice against lethal ectromelia virus (ECTV) infection, serving as an experimental model for severe systemic infections. Importantly, this early protective capacity of MVA vaccination completely depends on virus-specific cytotoxic CD8(+) T cell responses. We used MVA vaccination in the mousepox challenge model using ECTV infection to investigate the previously unknown factors required to elicit rapid protective T cell immunity in normal C57BL/6 mice and in mice lacking the interferon alpha/beta receptor (IFNAR(-/-)). We found a minimal dose of 10(5) PFU of MVA vaccine fully sufficient to allow robust protection against lethal mousepox, as assessed by the absence of disease symptoms and failure to detect ECTV in organs from vaccinated animals. Moreover, MVA immunization at low dosage also protected IFNAR(-/-) mice, indicating efficient activation of cellular immunity even in the absence of type I interferon signaling. When monitoring for virus-specific CD8(+) T cell responses in mice vaccinated with the minimal protective dose of MVA, we found significantly enhanced levels of antigen-specific T cells in animals that were MVA vaccinated and ECTV challenged compared to mice that were only vaccinated. The initial priming of naive CD8(+) T cells by MVA immunization appears to be highly efficient and, even at low doses, mediates a rapid in vivo burst of pathogen-specific T cells upon challenge. Our findings define striking requirements for protective emergency immunization against severe systemic infections with orthopoxviruses. IMPORTANCE We demonstrate that single-shot low-dose immunizations with vaccinia virus MVA can rapidly induce T cell-mediated protective immunity against lethal orthopoxvirus infections. Our data provide new evidence for an efficient protective capacity of vaccination with replication-deficient MVA. These data are of important practical relevance for public health, as the effectiveness of a safety-tested, next-generation smallpox vaccine based on MVA is still debated. Furthermore, producing sufficient amounts of vaccine is expected to be a major challenge should an outbreak occur. Moreover, prevention of other infections may require rapidly protective immunization; hence, MVA could be an extremely useful vaccine for delivering heterologous T cell antigens, particularly for infectious diseases that fit a scenario of emergency vaccination.", "qid": 49, "docid": "vdsrdxrn", "rank": 25, "score": 18.228599548339844}, {"content": "Title: Immunity to Infection Content: This chapter describes immune responses to the six major types of pathogens: extracellular bacteria, intracellular bacteria, viruses, parasites, fungi and prions. Innate immunity mediated by neutrophils, NK cells, NKT cells, \u03b3\u03b4 T cells, complement and microbicidal molecules prevents infection or slows it until adaptive immunity can also respond to the pathogen. Extracellular entities are coated in antibody and cleared by antibody- and complement-mediated mechanisms. Parasitic worms are prevented from anchoring in the host by IgA and IgE antibodies. IgE triggers mast cell, basophil and eosinophil degranulation and the release of toxic mediators. Intracellular bacteria and parasites as well as viruses are eliminated by CTLs, NK cells, NKT cells and \u03b3\u03b4 T cells secreting cytotoxic cytokines and/or carrying out target cell cytolysis. Macrophage hyperactivation and granuloma formation may be triggered to confine persistent invaders. Th1 and Th17 responses support cell-mediated immunity against internal threats, whereas Th2 responses support humoral immunity against external threats. Each type of pathogen has evolved to evade immune responses by avoiding recognition or inactivating various leukocyte effector mechanisms.", "qid": 49, "docid": "wpc5dmcz", "rank": 26, "score": 18.225799560546875}, {"content": "Title: Increased expression of CD8 marker on T-cells in COVID-19 patients Content: Abstract Background Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. Methods Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. Results The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). Conclusion Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.", "qid": 49, "docid": "pjwgrejn", "rank": 27, "score": 18.1737003326416}, {"content": "Title: Increased expression of CD8 marker on T-cells in COVID-19 patients Content: BACKGROUND: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. METHODS: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. RESULTS: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). CONCLUSION: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.", "qid": 49, "docid": "z6ytcze7", "rank": 28, "score": 18.17369842529297}, {"content": "Title: Induction of mucosal immune responses and protection against enteric viruses: rotavirus infection of gnotobiotic pigs as a model Content: Abstract Enteric viruses are a major cause of diarrhea in animals and humans. Among them, rotaviruses are one of the most important causes of diarrhea in young animals and human infants. A lack of understanding of mechanisms to induce intestinal immunity and the correlates of protective immunity in neonates has impaired development of safe and effective vaccines against enteric viruses. Studies of candidate vaccines using an adult mouse model of subclinical enteric viral infections often do not predict vaccine efficacy against disease evaluated in neonatal large animals. A series of studies have been conducted using a neonatal gnotobiotic pig model of rotavirus infection and diarrhea to identify correlates of protective immunity and to evaluate traditional and novel vaccine approaches for the induction of mucosal immune responses and protection to enteric viruses. Gnotobiotic pigs recovered from infection with virulent Wa human rotavirus (HRV) (mimic natural infection) had high numbers of intestinal IgA rotavirus-specific primary antibody-secreting cells (ASCs) and memory B-cells (to recall antigen) measured by ELISPOT assay, which correlated with complete protection against rotavirus challenge. Most short-term IgA memory B-cells were resident in the ileum, the major site of rotavirus replication. Spleen, not the bone marrow, was the major resident site for longer-term IgG memory B-cells. Candidate rotavirus vaccines evaluated in pigs for their ability to induce intestinal or systemic ASC and protection against rotavirus infection and diarrhea included attenuated live virus, inactivated virus, and baculovirus-expressed double-layered rotavirus-like particles (2/6-VLPs). In combination with those candidate vaccines, various adjuvants, delivery systems, and immunization routes were tested, including incomplete Freund\u2019s adjuvant for i.m. immunization, and a mutant Escherichia coli heat labile enterotoxin R192G (mLT) for i.n. immunization. It was shown that orally administered replicating vaccines were most effective for priming for intestinal IgA ASC and memory B-cell responses, but i.n. administered non-replicating 2/6-VLPs plus mLT were effective as booster vaccines. We conclude that protective immunity depends on the magnitude, location, viral protein-specificity, and isotype of the antibody responses induced by vaccination. Therefore highly effective enteric viral vaccines should: (i) induce sufficient levels of intestinal IgA antibodies; (ii) include viral antigens that induce neutralizing antibodies; and (iii) require the use of effective mucosal adjuvants or antigen delivery systems for non-replicating oral or i.n. vaccines.", "qid": 49, "docid": "bnjkmegh", "rank": 29, "score": 18.13640022277832}, {"content": "Title: Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19 Content: SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.", "qid": 49, "docid": "wdfzrzkt", "rank": 30, "score": 18.104299545288086}, {"content": "Title: Personalized workflow to identify optimal T-cell epitopes for peptide-based vaccines against COVID-19 Content: Traditional vaccines against viruses are designed to target their surface proteins, i.e., antigens, which can trigger the immune system to produce specific antibodies to capture and neutralize the viruses. However, viruses often evolve quickly, and their antigens are prone to mutations to avoid recognition by the antibodies (antigenic drift). This limitation of the antibody-mediated immunity could be addressed by the T-cell mediated immunity, which is able to recognize conserved viral HLA peptides presented on virus-infected cells. Thus, by targeting conserved regions on the genome of a virus, T-cell epitope-based vaccines are less subjected to mutations and may work effectively on different strains of the virus. Here we propose a personalized workflow to identify an optimal set of T-cell epitopes based on the HLA alleles and the immunopeptidome of an individual person. Specifically, our workflow trains a machine learning model on the immunopeptidome and then predicts HLA peptides from conserved regions of a virus that are most likely to trigger responses from the person T cells. We applied the workflow to identify T-cell epitopes for the SARS-COV-2 virus, which has caused the recent COVID-19 pandemic in more than 100 countries across the globe.", "qid": 49, "docid": "5aqzp5g1", "rank": 31, "score": 18.04800033569336}, {"content": "Title: Innate Immunity in Viral Encephalitis Content: Innate immune responses to pathogens are evolutionarily ancient and are found in the most primitive organisms. These are highly conserved and are not pathogen-specific, but are in response to classes of molecular structures. Infections can be perceived both extracellularly and intracellularly by Pathogen Associated Molecular Patterns (PAMPs) and their host cell ligands, Pathogen Recognition Receptors (PRRs), among them, Toll-Like Receptors (TLRs). The innate immune response to infection includes the release of soluble preformed mediators, or synthesis of cytoplasmic enzymes, cytokines, chemokines, interferons (IFNs), lipid mediators, proteins of the complement cascade, neurotransmitters, nucleotides, and components of transcription factors (High Mobility Group B1, receptors for sex hormones/steroids). Directed cellular migration of parenchymal astrocytes and microglia, as well as recruitment across the blood brain barrier (BBB) of circulating neutrophils, natural killer, monocytes, macrophages, dendritic cells, and ultimately T lymphocytes to the site of infection are also hallmarks of innate responses to infections. These responding cells contribute their own secreted effector molecules and effector activities (such as phagocytosis). Distinct viruses are capable of infecting every cell type (endothelial cells, ependymal cells, perivascular macrophages and pericytes, astrocytes, microglia, oligodendrocytes, Schwann cells, and neurons) in the central nervous system (CNS). These CNS infections challenge the host with a different set of problems than do peripheral viral infections. Among the complications are (a) neurons that rarely express Class I or Class II Major Histocompatibility Complex (MHC) molecules and are thus not suitable targets for either CD4(+) or CD8(+) MHC-restricted T cells, (b) an enclosed volume that is constrained from swelling during inflammation, as well as poorly developed lymphatic drainage, and (c) the immunologic privilege of the CNS which leads to extremely limited immune surveillance for pathogens. Therefore, the role of innate immunity, both from CNS-resident cells and their products, and from circulating inflammatory cells and molecules which traverse the BBB are essential to \u201cbuy time,\u201d inhibiting viral replication and dissemination, until the host can marshal an adaptive immune response. The immune responses are crucial for host survival from the infection. Consequently, successful pathogens, especially those that persist, have developed a wide variety of evasive approaches to limit the inhibition of replication. Many of these pathways are highlighted in individual chapters that precede this one. These evasive measures range from neutralizing host secreted molecules (cytokines and chemokines) with soluble receptors, encoding anti-inflammatory proteins in their genome, preventing signal transduction, blocking inhibition of protein synthesis, degradation of essential antiviral molecules, preventing apoptosis, and blockade of the nuclear pore complex. In this chapter, I will attempt to cover the breadth of the innate immune response to viral infection, but will also devote more space to generally under-considered aspects than to the well-known components. There are some caveats to consider, as most experiments have been performed in the murine model and not in man; further, conclusions from experiments using in vitro cultured cells (whether primary or established lines) may not reflect physiological conditions in an undisturbed CNS. Lastly, we now appreciate the complexities imposed on hosts by polymorphisms in genes of critical pathways, leading to increased susceptibility or resistance of that individual but not others.", "qid": 49, "docid": "x3oyp4w5", "rank": 32, "score": 18.043100357055664}, {"content": "Title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals Content: Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to \u201ccommon cold\u201d human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.", "qid": 49, "docid": "05djnz4p", "rank": 33, "score": 18.03459930419922}, {"content": "Title: Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? Content: The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19 Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut Immunotherapy with IVIg could be employed to neutralize COVID-19 However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 &deg;C heat-treatment, and nanofiltration Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available", "qid": 49, "docid": "d4sjferd", "rank": 34, "score": 17.995800018310547}, {"content": "Title: Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? Content: The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 \u00b0C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.", "qid": 49, "docid": "ix4zo0ha", "rank": 35, "score": 17.995798110961914}, {"content": "Title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus Content: The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. In the experiment, we immunized four groups of piglets with two commercial inactivated (A1\u2014Progressis, A2\u2014Suivac) and two modified live vaccines (B3\u2014Amervac, B4\u2014Porcilis). Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. The serum antibody response (IgM and IgG) was the strongest in group A1 followed by two MLV (B3 and B4) groups. Locally, we demonstrated the highest level of IgG antibodies in bronchoalveolar lavages (BALF), and saliva in group A1, whereas low IgA antibody responses in BALF and feces were detected in all groups. We have found virus neutralization antibody at DPV 21 (days post vaccination) and higher levels in all groups including the control at DPI 21 (days post infection). Positive antigen specific cell-mediated response in lymphocyte transformation test (LTT) was observed in groups B3 and B4 at DPV 7 and in group B4 at DPV 21 and in all intervals after infection. The IFN-\u03b3 producing lymphocytes after antigen stimulation were found in CD4(\u2212)CD8(+) and CD4(+)CD8(+) subsets of all immunized groups 7 days after infection. After infection, there were obvious differences in virus excretion. The virus was detected in all groups of piglets in serum, saliva, and occasionally in feces at DPI 3. Significantly lower virus load was found in groups A1 and B3 at DPI 21. Negative samples appeared at DPI 21 in B3 group in saliva. It can be concluded that antibodies after immunization and infection, and the virus after infection can be detected in all the compartments monitored. Immunization with inactivated vaccine A1\u2014Progressis induces high levels of antibodies produced both systemically and locally. Immunization with MLV-vaccines (Amervac and Porcilis) produces sufficient antibody levels and also cell-mediated immunity. After infection virus secretion gradually decreases in group B3, indicating tendency to induce sterile immunity.", "qid": 49, "docid": "tkqxb1ql", "rank": 36, "score": 17.973600387573242}, {"content": "Title: A possible role of immunopathogenesis in COVID-19 progression Content: Background: The efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities. Methods: In this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity. Results: Significantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression. Conclusion: Our data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.", "qid": 49, "docid": "in91dr4g", "rank": 37, "score": 17.94879913330078}, {"content": "Title: Lack of cytomegalovirus (CMV)-specific cell-mediated immune response using QuantiFERON-CMV assay in CMV-seropositive healthy volunteers: fact not artifact. Content: The QuantiFERON-CMV (QF) assay measures cell-mediated immunity against cytomegalovirus (CMV-CMI), which is particularly useful in individuals susceptible to CMV infection such as transplant patients. A positive QF result identifies patients that are better protected against CMV infection. However, the significance of a negative QF result in CMV-seropositive individuals needs to be clarified. CMV-CMI was analyzed in healthy subjects using the QF assay, and, in parallel, the Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA). FASCIA assay measures T-cell proliferation using CMV lysate as stimulus whereas QF assay use a mix of peptides. A total of 93 healthy volunteers were enrolled, and 13/71 CMV-seropositive individuals (18.3%) showed humoral/cellular discordance using QF assay (CMV+ QF-). Interestingly, with FASCIA assay CD4+ and CD8+ T-cell proliferations were lower in CMV+ QF- than in CMV+ QF+ individuals. Furthermore, CMV+ QF- volunteers had a lower level of anti-CMV IgG than CMV+ QF+ subjects. Discordant CMV+ QF- volunteers can be defined as low responder individuals since they show lower CMV-specific humoral and cellular immune responses in comparison to CMV+ QF+ individuals. Immune discordance shows the high heterogeneity of immunity to CMV in healthy subjects.", "qid": 49, "docid": "4hgx91xi", "rank": 38, "score": 17.834299087524414}, {"content": "Title: Lack of cytomegalovirus (CMV)-specific cell-mediated immune response using QuantiFERON-CMV assay in CMV-seropositive healthy volunteers: fact not artifact Content: The QuantiFERON-CMV (QF) assay measures cell-mediated immunity against cytomegalovirus (CMV-CMI), which is particularly useful in individuals susceptible to CMV infection such as transplant patients. A positive QF result identifies patients that are better protected against CMV infection. However, the significance of a negative QF result in CMV-seropositive individuals needs to be clarified. CMV-CMI was analyzed in healthy subjects using the QF assay, and, in parallel, the Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA). FASCIA assay measures T-cell proliferation using CMV lysate as stimulus whereas QF assay use a mix of peptides. A total of 93 healthy volunteers were enrolled, and 13/71 CMV-seropositive individuals (18.3%) showed humoral/cellular discordance using QF assay (CMV+ QF-). Interestingly, with FASCIA assay CD4+ and CD8+ T-cell proliferations were lower in CMV+ QF- than in CMV+ QF+ individuals. Furthermore, CMV+ QF- volunteers had a lower level of anti-CMV IgG than CMV+ QF+ subjects. Discordant CMV+ QF- volunteers can be defined as low responder individuals since they show lower CMV-specific humoral and cellular immune responses in comparison to CMV+ QF+ individuals. Immune discordance shows the high heterogeneity of immunity to CMV in healthy subjects.", "qid": 49, "docid": "b8d6r7tm", "rank": 39, "score": 17.83429718017578}, {"content": "Title: Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies. Content: The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV vaccine, were primarily nonneutralizing. In contrast, most of the antibodies to the complex formed by gH, gL, protein (p)UL128, pUL130, and pUL131 (the gHgLpUL128L pentamer) neutralized HCMV infection with high potency. Based on this analysis, we developed a single polycistronic vector encoding the five pentamer genes separated by \"self-cleaving\" 2A peptides to generate a stably transfected CHO cell line constitutively secreting high levels of recombinant pentamer that displayed the functional antigenic sites targeted by human neutralizing antibodies. Immunization of mice with the pentamer formulated with different adjuvants elicited HCMV neutralizing antibody titers that persisted to high levels over time and that were a hundred- to thousand-fold higher than those found in individuals that recovered from primary HCMV infection. Sera from mice immunized with the pentamer vaccine neutralized infection of both epithelial cells and fibroblasts and prevented cell-to-cell spread and viral dissemination from endothelial cells to leukocytes. Neutralizing monoclonal antibodies from immunized mice showed the same potency as human antibodies and targeted the same as well as additional sites on the pentamer. These results illustrate with a relevant example a general and practical approach of analytic vaccinology for the development of subunit vaccines against complex pathogens.", "qid": 49, "docid": "i4e7z0hg", "rank": 40, "score": 17.814899444580078}, {"content": "Title: The art of survival during viral persistence. Content: Central nervous system infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in chronic demyelination characterized by viral persistence in the absence of infectious virus. CD8(+) T cells inhibit acute viral replication via cell type-specific effector mechanisms. Perforin-mediated cytolysis controls virus in microglia/macrophages and astrocytes, whereas interferon (IFN)-gamma regulates viral replication in oligodendroglia. JHMV infection of antibody-deficient mice confirmed a primary role of cellular immunity and a redundant role for humoral immunity during acute infection. However, infectious virus reactivates in antibody-deficient mice following viral clearance. This observation suggests that virus-specific T cells in the central nervous system are unable to control viral persistence. Reactivation in antibody-deficient mice is not associated with increased T-cell infiltration, but is prevented via transfer of neutralizing antibody. A vital role for humoral immunity during persistence is supported by the accumulation and retention of virus-specific antibody secreting cells following clearance of infectious virus. Thus, cell-mediated immune responses control acute infection, whereas humoral immunity maintains viral persistence. Therefore, although the central nervous system provides an environment for prolonged retention of both T cells and plasma cells, plasma cells are critical in maintaining persistent virus at undetectable levels. The low turnover of virus, T cells, and B cells constitute a unifying feature of persistent infection, illustrating the dichotomy between distinct immune effectors in regulating acute and persistent central nervous system infection.", "qid": 49, "docid": "acmjghym", "rank": 41, "score": 17.777000427246094}, {"content": "Title: SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing Content: Objective: The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in the lung of COVID-19 patients. Design: We analyzed single-cell RNA sequencing (scRNA-seq) data of lung samples from 17 subjects (6 severe COVID-19 patients, 3 mild patients who recovered and 8 healthy controls). The expression of SARS-CoV-2 receptors (ACE2 and TMPRSS2) was examined among different cell types in the lung. The immune cells infiltration patterns, their gene expression profiles, and the interplay of immune cells and SARS-CoV-2 target cells were further investigated. Results: Compared to healthy controls, the overall ACE2 (receptor of SARS-CoV-2) expression was significantly higher in lung epithelial cells of COVID-19 patients, in particular in ciliated cell, club cell and basal cell. Comparative transcriptome analysis of these lung epithelial cells of COVID-19 patients and healthy controls identified that SARS-CoV-2 infection activated pro-inflammatory signaling including interferon pathway and cytokine signaling. Moreover, we identified dysregulation of immune response in patients with COVID-19. In severe COVID-19 patients, significantly higher neutrophil, but lower T and NK cells in lung were observed along with markedly increased cytokines (CCL2, CCL3, CCL4, CCL7, CCL3L1 and CCL4L2) compared with healthy controls as well as mild patients who recovered. The cytotoxic phenotypes were shown in lung T and NK cells of severe patients as evidenced by enhanced IFN{gamma}, Granulysin, Granzyme B and Perforin expression. Moreover, SARS-CoV-2 infection altered the community interplay of lung epithelial cells and immune cells: the interaction between epithelial cells with macrophage, T and NK cell was stronger, but their interaction with neutrophils was lost in COVID-19 patients compared to healthy controls. Conclusions: SARS-CoV-2 infection activates pro-inflammatory signaling in lung epithelial cells expressing ACE2 and causes dysregulation of immune response to release more pro-inflammatory cytokines. Moreover, SARS-CoV-2 infection breaks the interplay of lung epithelial cells and immune cells.", "qid": 49, "docid": "08p8ns2d", "rank": 42, "score": 17.715299606323242}, {"content": "Title: Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents Content: Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8+ lymphocytes and NK cells were significantly reduced in cases of severe infection compared to patients with mild infection and healthy individuals. The NK group 2 member A (NKG2A) receptor transduces inhibitory signalling, suppressing NK cytokine secretion and cytotoxicity. Overexpression of NKG2A has been observed on CD8+ and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8+ cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8+ cells and NK cells in cancers modulated tumor growth, restoring CD8+ T and NK cell function. A recently proposed mechanism via which SARS-CoV-2 overrides innate immune response of the host is by over-expressing NKG2A on CD+ T and NK cells, culminating in functional exhaustion of the immune response against the viral pathogen. Monalizumab is an inhibiting antibody against NKG2A which can restore the function of CD8 + T and NK cells in cancers, successfully ceasing tumor progression with no significant side effects in Phase 2 clinical trials. We hypothesize that patients with severe COVID-19 have a severely compromised innate immune response and could be treated via the use of Monalizumab, interferon &#945;, chloroquine, and other antiviral agents.", "qid": 49, "docid": "l9mbrdej", "rank": 43, "score": 17.68720054626465}, {"content": "Title: Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents Content: Abstract Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8+ lymphocytes and NK cells were significantly reduced in cases of severe infection compared to patients with mild infection and healthy individuals. The NK group 2 member A (NKG2A) receptor transduces inhibitory signalling, suppressing NK cytokine secretion and cytotoxicity. Overexpression of NKG2A has been observed on CD8+ and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8+ cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8+ cells and NK cells in cancers modulated tumor growth, restoring CD8+ T and NK cell function. A recently proposed mechanism via which SARS-CoV-2 overrides innate immune response of the host is by over-expressing NKG2A on CD+ T and NK cells, culminating in functional exhaustion of the immune response against the viral pathogen. Monalizumab is an inhibiting antibody against NKG2A which can restore the function of CD8 + T and NK cells in cancers, successfully ceasing tumor progression with no significant side effects in Phase 2 clinical trials. We hypothesize that patients with severe COVID-19 have a severely compromised innate immune response and could be treated via the use of Monalizumab, interferon \u03b1, chloroquine, and other antiviral agents.", "qid": 49, "docid": "tqziaq1m", "rank": 44, "score": 17.687198638916016}, {"content": "Title: Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective. Content: Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)-\uf062 production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved by clinical trials based on RAS blo", "qid": 49, "docid": "vslevssr", "rank": 45, "score": 17.630300521850586}, {"content": "Title: Beyond the Spike: identification of viral targets of the antibody response to SARS-CoV-2 in COVID-19 patients Content: Background: The SARS-CoV-2 virus emerged in December 2019 and caused a pandemic associated with a spectrum of COVID-19 disease ranging from asymptomatic to lethal infection. Serology testing is important for diagnosis of infection, determining infection attack rates and immunity in the population. It also informs vaccine development. Although several serology tests are in use, improving their specificity and sensitivity for early diagnosis on the one hand and for detecting past infection for population-based studies, are priorities. Methods: We evaluated the anti-SARS-CoV-2 antibody profiles to 15 SARS-CoV-2 antigens by cloning and expressing 15 open reading frames (ORFs) in mammalian cells and screened antibody responses to them in COVID-19 patients using the Luciferase Immunoprecipitation System (LIPS). Results: The LIPS technique allowed us to detect antibody responses in COVID-19 patients to 11 of the 15 SARS-CoV-2 antigens tested, identifying novel immunogenic targets. This technique shows that antigens ORF3b and ORF8 allow detection of antibody early in infection in a specific manner and reveals the immuno-dominance of the N antigen in COVID-19 patients. Conclusion: Our report provides an unbiased characterization of antibody responses to a range of SARS-CoV-2 antigens. The combination of 3 SARS-CoV-2 antibody LIPS assays, i.e. N, ORF3b, and ORF8, is sufficient to identify all COVID-19 patients of our cohort even at early time-points of illness, whilst Spike alone fails to do so. Furthermore, our study highlights the importance of investigating new immunogens NSP1, ORF3b, ORF7a and ORF8 which may mediate immune functions other than neutralization which may be beneficial or harmful to the patient.", "qid": 49, "docid": "t9jo76ja", "rank": 46, "score": 17.61079978942871}, {"content": "Title: Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important? Content: Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.", "qid": 49, "docid": "3894l9qi", "rank": 47, "score": 17.587200164794922}, {"content": "Title: Immune Response to Viruses: Antibody-Mediated Immunity Content: The notion about immunity to disease arose from the observation that those who recovered from an apparently contagious disease became resistant to a subsequent similar sickness. Much later it was shown that immunity is transferable by serum. The active serum components were identified to be immunoglobulins (Ig's), called antibodies. The enormous diversity of antibodies specific for distinct viruses, pathogens, and many other antigens is explained by clonal selection, whereby specific B-lymphocyte receptors recognize a particular antigen. The selected B-cells are triggered to undergo replication. A process of further cell differentiation and maturation ensues, leading to secretion of antibodies with high binding affinity toward the triggering antigen. Genes coding for the variable regions (involved in antigen binding) of Ig's are inherited as sets of gene fragments joined to form a complete gene in individual B-cells. This process and further hypermutations ensure the synthesis of diverse high affinity antibodies. The antibodies consist of pairs of light (L) and heavy (H) polypeptide chains. Variations in the constant portion of H-chains lead to production of Ig isotypes (IgM, IgA, IgD, IgE, and IgG (further subdivided into IgG1, IgG2, IgG3 and IgG4)), each having distinct effector functions. Host exposure to viruses leads to the production of antibodies with more than one specificity. Only some of these antibodies, recognizing so-called virus neutralization epitopes, diminish or eliminate virus infectivity. Other virus-specific antibodies play auxiliary roles or are ineffective. Sometimes antibodies cause enhancement of viral diseases or play a role in evasion of the immune system. Many antiviral immunoglobulins are being used for short-term pre-exposure prophylaxis or therapy. Long-term protective effects can be accomplished only by antibodies elicited by successful vaccination relying on the phenomenon of immunological memory. T-lymphocytes play a major role in initiating and maintaining immunity against subsequent virus exposure. Antibodies are one of the essential features of antigen triggered adaptive immunity. Initial early defense against viruses is provided by components of innate immunity which evolutionarily precedes adaptive immunity, and remains an essential part of defense against pathogens in humans.", "qid": 49, "docid": "6tgyvmnv", "rank": 48, "score": 17.563100814819336}, {"content": "Title: Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine Content: Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.", "qid": 49, "docid": "e8k72955", "rank": 49, "score": 17.47010040283203}, {"content": "Title: Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants. Content: Both CD4(+) and CD8(+) T cells are required for clearance of the murine coronavirus mouse hepatitis virus (MHV) during acute infection. We investigated the effects of an epitope-specific CD8(+) T-cell response on acute infection of MHV, strain A59, in the murine CNS. Mice with CD8(+) T cells specific for gp33-41 (an H-2D(b)-restricted CD8(+) T-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant MHV-A59, also expressing gp33-41, as a fusion protein with enhanced green fluorescent protein (EGFP). By 5 days postinfection, these mice showed significantly (approximately 20-fold) lower titers of infectious virus in the brain compared to control mice. Furthermore mice with gp33-41-specific CD8(+) cells exhibited much reduced levels of viral antigen in the brain as measured by immunohistochemistry using an antibody directed against viral nucleocapsid. More than 90% of the viruses recovered from brain lysates of such protected mice, at 5 days postinfection, had lost the ability to express EGFP and had deletions in their genomes encompassing EGFP and gp33-41. In addition, genomes of viruses from about half the plaques that retained the EGFP gene had mutations within the gp33-41 epitope. On the other hand, gp33-41-specific cells failed to protect perforin-deficient mice from infection by the recombinant MHV expressing gp33, indicating that perforin-mediated mechanisms were needed. Virus recovered from perforin-deficient mice did not exhibit loss of EGFP expression and the gp33-41 epitope. These observations suggest that the cytotoxic T-cell response to gp33-41 exerts a strong immune pressure that quickly selects epitope escape mutants to gp33-41.", "qid": 49, "docid": "dwn5pq1d", "rank": 50, "score": 17.467199325561523}, {"content": "Title: Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1\u20135). Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 49, "docid": "nhkd88yv", "rank": 51, "score": 17.427799224853516}, {"content": "Title: Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 49, "docid": "1w7g6dkq", "rank": 52, "score": 17.40679931640625}, {"content": "Title: Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus Content: BACKGROUND: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. METHODS: We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable \u03b3 receptors (Fc\u03b3R), which bind antibody-coated pathogens. RESULTS: We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human Fc\u03b3RII family, which were shown to confer susceptibility to otherwise na\u00efve ST486 cells, as binding of immune complexes to cell surface Fc\u03b3RII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only Fc\u03b3RII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by Fc\u03b3RII. CONCLUSIONS: These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to Fc\u03b3RII receptors.", "qid": 49, "docid": "a8ntxnmm", "rank": 53, "score": 17.312400817871094}, {"content": "Title: T helper cell- and CD40-dependent germline IgM prevents chronic virus-induced demyelinating disease. Content: Generation of antiviral IgM is usually considered as a marker of a short-lived initial antibody response that is replaced by hypermutated and more-efficient IgG. However, once viruses have established a particular niche for their persistence (e.g., within the CNS), the immune system has to specifically mobilize a broad range of antimicrobial effectors to contain the pathogen in the long term. Infection of the CNS with the mouse hepatitis virus (MHV) provides a unique model situation in which the extent of inflammatory CNS disease is determined by the balance between antiviral immune control, viral replication, and immune-mediated damage. We show here that whereas antibody- or B cell-deficient mice failed to contain MHV CNS infection and developed progressive demyelinating disease, germline IgM produced in activation-induced cytidine deaminase-deficient mice (aicda(-/-)) provided long-term protection against the chronic multiple sclerosis-like disease. Furthermore, we found that appropriate B-cell activation within the CNS-draining lymph node and subsequent CXCR3-mediated migration of antiviral IgM-secreting cells to the infected CNS was dependent on CD40-mediated interaction of B cells with T helper cells. These data indicate that the CD40-mediated collaboration of T and B cells is critical to secure neuroprotective IgM responses during viral CNS infection.", "qid": 49, "docid": "toy3ylym", "rank": 54, "score": 17.28689956665039}, {"content": "Title: Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity Content: In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1 (-/-) recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.", "qid": 49, "docid": "85yd3h2b", "rank": 55, "score": 17.284799575805664}, {"content": "Title: B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein. Content: Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunopathology.", "qid": 49, "docid": "m16xmyv0", "rank": 56, "score": 17.256999969482422}, {"content": "Title: CD8(+) T cells in HIV control, cure and prevention Content: HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy, but an effective vaccine will likely be required to end the HIV epidemic. Although the majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8(+) T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review, we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8(+) T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies.", "qid": 49, "docid": "wu2lxfty", "rank": 57, "score": 17.242900848388672}, {"content": "Title: Is copper beneficial for COVID-19 patients? Content: Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS-CoV-2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS-CoV-2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19.", "qid": 49, "docid": "99j9qqg3", "rank": 58, "score": 17.197099685668945}, {"content": "Title: Is Copper beneficial for COVID-19 patients? Content: Abstract Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS\u2010CoV\u20102. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS\u2010CoV\u20102. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19.", "qid": 49, "docid": "d1nh2dvb", "rank": 59, "score": 17.197097778320312}, {"content": "Title: Convergent antibody responses to SARS-CoV-2 in convalescent individuals Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 49, "docid": "79891dfu", "rank": 60, "score": 17.14590072631836}, {"content": "Title: Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 49, "docid": "gof2of9o", "rank": 61, "score": 17.145898818969727}, {"content": "Title: Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective Content: Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)-\u00ef\u0081\u00a2 production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved byclinical trials based on RAS blockade or initiation and monitoring related effects. Contemporarily, Danser and associates [51] claim that there is no evidence to stop RAS blockers in the course of COVID-19 infection. In fact, there are no available data which support that ACE inhibitors or ANG II type I receptor blockers increase COVID-19 infection via its binding to ACE2. Finally, Kuster and associates [52] write that there are no data on the strict relationship between ACE2 activity and SARS-CoV2 mortality. Moreover, in the SARSCoV2, cells expressing ACE2 were not attacked by the virus, while cells lacking ACE2 were bound by the SARS-CoV2 virus [53]. These findings suggest that also in the case of RES effects on COVID-19 infection, the dual role of ACE2 should be taken into serious consideration.", "qid": 49, "docid": "lqdgvsaq", "rank": 62, "score": 17.121599197387695}, {"content": "Title: Control of HPV-associated tumors by innovative therapeutic HPV DNA vaccine in the absence of CD4+ T cells Content: Human papillomavirus (HPV) infections are particularly problematic for HIV + and solid organ transplant patients with compromised CD4+ T cell-dependent immunity as they produce more severe and progressive disease compared to healthy individuals. There are no specific treatments for chronic HPV infection, resulting in an urgent unmet need for a modality that is safe and effective for both immunocompromised and otherwise normal patients with recalcitrant disease. DNA vaccination is attractive because it avoids the risks of administration of live vectors to immunocompromised patients, and can induce potent HPV-specific cytotoxic T cell responses. We have developed a DNA vaccine (pNGVL4a-hCRTE6E7L2) encoding calreticulin (CRT) fused to E6, E7 and L2 proteins of HPV-16, the genotype associated with approximately 90% vaginal, vulvar, anal, penile and oropharyngeal HPV-associated cancers and the majority of cervical cancers. Administration of the DNA vaccine by intramuscular (IM) injection followed by electroporation induced significantly greater HPV-specific immune responses compared to IM injection alone or mixed with alum. Furthermore, pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation of mice carrying an intravaginal HPV-16 E6/E7-expressing syngeneic tumor demonstrated more potent therapeutic effects than IM vaccination alone. Of note, administration of the DNA vaccine by IM injection followed by electroporation elicited potent E6 and E7-specific CD8+ T cell responses and antitumor effects despite CD4+ T cell-depletion, although no antibody response was detected. While CD4+ T cell-depletion did reduce the E6 and E7-specific CD8+ T cell response, it remained sufficient to prevent subcutaneous tumor growth and to eliminate circulating tumor cells in a model of metastatic HPV-16+ cancer. Thus, the antibody response was CD4-dependent, whereas CD4+ T cell help enhanced the E6/E7-specific CD8+ T cell immunity, but was not required. Taken together, our data suggest that pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation warrants testing in otherwise healthy patients and those with compromised CD4+ T cell immunity to treat HPV-16-associated anogenital disease and cancer.", "qid": 49, "docid": "okpdkjd3", "rank": 63, "score": 17.104299545288086}, {"content": "Title: Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals Content: Background Lymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. Methods A clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. Findings Compared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. Interpretation The CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions.", "qid": 49, "docid": "avhxj8jk", "rank": 64, "score": 17.08930015563965}, {"content": "Title: Immunogenic profile of SARS-CoV-2 spike in individuals recovered from COVID-19 Content: The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronavirus immunity to expedite vaccine development efforts. Multiple candidate vaccines, designed to elicit protective neutralising antibodies targeting the viral spike glycoprotein, are rapidly advancing to clinical trial. However, the immunogenic properties of the spike protein in humans are unresolved. To address this, we undertook an in-depth characterisation of humoral and cellular immunity against SARS-CoV-2 spike in humans following mild to moderate SARS-CoV-2 infection. We find serological antibody responses against spike are routinely elicited by infection and correlate with plasma neutralising activity and capacity to block ACE2/RBD interaction. Expanded populations of spike-specific memory B cells and circulating T follicular helper cells (cTFH) were detected within convalescent donors, while responses to the receptor binding domain (RBD) constitute a minor fraction. Using regression analysis, we find high plasma neutralisation activity was associated with increased spike-specific antibody, but notably also with the relative distribution of spike-specific cTFH subsets. Thus both qualitative and quantitative features of B and T cell immunity to spike constitute informative biomarkers of the protective potential of novel SARS-CoV-2 vaccines.", "qid": 49, "docid": "fwn97wds", "rank": 65, "score": 17.066699981689453}, {"content": "Title: Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS) coronavirus in recovered SARS patients and healthy individuals. Content: To date, the pathogenesis of severe acute respiratory syndrome (SARS) in humans is still not well understood. SARS coronavirus (SARS-CoV)-specific CTL responses, in particular their magnitude and duration of postinfection immunity, have not been extensively studied. In this study, we found that heat-inactivated SARS-CoV elicited recall CTL responses to newly identified spike protein-derived epitopes (SSp-1, S978, and S1202) in peripheral blood of all HLA-A*0201(+) recovered SARS patients over 1 year postinfection. Intriguingly, heat-inactivated SARS-CoV elicited recall-like CTL responses to SSp-1 but not to S978, S1202, or dominant epitopes from several other human viruses in 5 of 36 (13.8%) HLA-A*0201(+) healthy donors without any contact history with SARS-CoV. SSp-1-specific CTLs expanded from memory T cells of both recovered SARS patients, and the five exceptional healthy donors shared a differentiated effector CTL phenotype, CD45RA(+)CCR7(-)CD62L(-), and expressed CCR5 and CD44. However, compared with the high avidity of SSp-1-specific CTLs derived from memory T cells of recovered SARS patients, SSp-1-specific CTLs from the five exceptional healthy donors were of low avidity, as determined by their rapid tetramer dissociation kinetics and reduced cytotoxic reactivity, IFN-gamma secretion, and intracellular production of IFN-gamma, TNF-alpha, perforin, and granzyme A. These results indicate that SARS-CoV infection induces strong and long-lasting CTL-mediated immunity in surviving SARS patients, and that cross-reactive memory T cells to SARS-CoV may exist in the T cell repertoire of a small subset of healthy individuals and can be reactivated by SARS-CoV infection.", "qid": 49, "docid": "vnzp9cno", "rank": 66, "score": 17.06399917602539}, {"content": "Title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition Content: It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 \"don't eat me\" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.IMPORTANCE Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.", "qid": 49, "docid": "0vz0ilkj", "rank": 67, "score": 17.06279945373535}, {"content": "Title: SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors Content: Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.", "qid": 49, "docid": "ioihqf0r", "rank": 68, "score": 17.060699462890625}, {"content": "Title: Prevention of virus persistence and protection against immunopathology after Borna disease virus infection of the brain by a novel Orf virus recombinant. Content: The Parapoxvirus Orf virus represents a promising candidate for novel vector vaccines due to its immune modulating properties even in nonpermissive hosts such as mouse or rat. The highly attenuated Orf virus strain D1701 was used to generate a recombinant virus (D1701-VrVp40) expressing nucleoprotein p40 of Borna disease virus, which represents a major antigen for the induction of a Borna disease virus-specific humoral and cellular immune response. Infection with Borna disease virus leads to distinct neurological symptoms mediated by the invasion of activated specific CD8+ T cells into the infected brain. Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells. In the present study we show for the first time that intramuscular application of the D1701-VrVp40 recombinant protected rats against Borna disease, and importantly, virus clearance from the infected brain was demonstrated in immunized animals. Even 4 and 8 months after the last immunization, all immunized animals were still protected against the disease. Initial characterization of the immune cells attracted to the infected brain areas suggested that D1701-VrVp40 mediated induction of B cells and antibody-producing plasma cells as well as T cells. These findings suggest the induction of various defense mechanisms against Borna disease virus. First studies on the role of antiviral cytokines indicated that D1701-VrVp40 immunization did not lead to an enhanced early response of gamma or alpha interferon or tumor necrosis factor alpha. Collectively, this study describes the potential of the Orf virus vector system in mediating long-lasting, protective antiviral immunity and eliminating this persistent virus infection without provoking massive neuronal damage.", "qid": 49, "docid": "p4evg1xb", "rank": 69, "score": 17.045299530029297}, {"content": "Title: Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID \u201019 infected patients Content: COVID\u201019 pandemic is an emerging new human disease, where no vaccines, or monoclonal antibodies (mAbs), or drugs are currently available for therapy. Active vaccination requires the induction of an immune response against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease and this usually takes time to develop. Thus, the use of existing autologous Ab administration, obtainable from recovered COVID 19 patients, after 2 weeks recovery, is the best and the most practical strategy for providing immediate passive immunity to susceptible recipients in need.", "qid": 49, "docid": "w8c3ma8l", "rank": 70, "score": 17.043800354003906}, {"content": "Title: T-cell immune responses in the brain and their relevance for cerebral malignancies. Content: In order that cellular immune responses afford protection without risk to sensitive normal tissue, they must be adapted to individual tissues of the body. Nowhere is this more critical than for the brain, where various passive and active mechanisms maintain a state of immune privilege that can limit high magnitude immune responses. Nevertheless, it is now clear that immune responses are induced to antigens in the brain, including those expressed by cerebral malignancies. We discuss hypotheses of how this can occur, although details such as which antigen presenting cells are involved remain to be clarified. Antitumor responses induced spontaneously are insufficient to eradicate malignant astrocytomas; many studies suggest that this can be explained by a combination of low level immune response induction and tumor mediated immunosuppression. A clinical objective currently pursued is to use immunotherapy to ameliorate antitumour immunity. This will necessitate a high level immune response to ensure sufficient effector cells reach the tumor bed, focused cytotoxicity to eradicate malignant cells with little collateral damage to critical normal cells, and minimal inflammation. To achieve these aims, priority should be given to identifying more target antigens in astrocytoma and defining those cells present in the brain parenchyma that are essential to maintain antitumour effector function without exacerbating inflammation. If we are armed with better understanding of immune interactions with brain tumor cells, we can realistically envisage that immunotherapy will one day offer hope to patients with currently untreatable neoplastic diseases of the CNS.", "qid": 49, "docid": "9dc375mu", "rank": 71, "score": 17.037500381469727}, {"content": "Title: Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus. Content: Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopovo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract--the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils (near the distal end of the tract), rectum and cloaca (the common opening for release of eggs and faeces), usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks do not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced alphabeta T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.", "qid": 49, "docid": "94dughd1", "rank": 72, "score": 17.006799697875977}, {"content": "Title: Recovery from Infection Content: This chapter discusses the immunological factors associated in the recovery of host from infections. Antibody, T cells, natural killer cells, complement, phagocytes, and interferon are involved in the response to nearly all infections and, without any doubt, are together responsible for recovery. There is good evidence that T-cell-mediated immunity is of supreme importance in recovery from a variety of microbial infections. These are the infections in which the microorganism replicates intracellularly. Tissue responses in the host bear the hallmarks of T-cell involvement, the infiltrating cells consisting primarily of lymphocytes and macrophages. Inflammation, whether induced by immunological reactions, tissue damage or microbial products, plays a vital role in recovery from infection. Inflammation is necessary for the proper functioning of the immune defenses because it focuses all circulating antimicrobial factors onto the site of infection. Complement can carry out antimicrobial activities. However, there is little direct evidence that the antimicrobial activities of complement are in fact important in the body. Interferons also act on uninfected cells, binding to a cell surface receptor and activating a number of genes involved in immunity to viruses. Multimechanistic recovery is illustrated in the chapter and other issues, such as the role of temperature, tissue repair, and resistance to re-infection are discussed.", "qid": 49, "docid": "s9vh337n", "rank": 73, "score": 16.99920082092285}, {"content": "Title: Suppression of innate immune pathology by regulatory T cells during Influenza A virus infection of immunodeficient mice. Content: The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virus-neutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.", "qid": 49, "docid": "wbnm7v27", "rank": 74, "score": 16.986299514770508}, {"content": "Title: Roosting ecology and variation in adaptive and innate immune system function in the Brazilian free-tailed bat (Tadarida brasiliensis) Content: Bats have recently been implicated as reservoirs of important emerging diseases. However, few studies have examined immune responses in bats, and even fewer have evaluated these responses in an ecological context. We examined aspects of both innate and adaptive immune response in adult female Brazilian free-tailed bats (Tadarida brasiliensis) at four maternity roosts (two natural caves and two human-made bridges) in south-central Texas. Immune measurements included in vitro bactericidal ability of whole blood and in vivo T cell mediated response to mitogenic challenge. Bactericidal activity in T. brasiliensis varied with roosting ecology, but appears to be sensitive to colony-level effects. Blood from females living at one cave had significantly lower bactericidal ability than blood from females at three other sites. T cell mediated response in this species was associated with variation in roost ecology, with females from two caves having greater responses than females from two bridges. T cell mediated response and bactericidal activity were negatively correlated with one another within individuals that were tested for both. Variation in immunological response of T. brasiliensis is important for understanding the influence of the environment on the frequency and distribution of immunologically competent individuals and for understanding disease-host dynamics in this and other colonial species.", "qid": 49, "docid": "77xij0fc", "rank": 75, "score": 16.98200035095215}, {"content": "Title: Immune response to SARS\u2010CoV\u20102 and mechanisms of immunopathological changes in COVID\u201019 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID\u201019) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to detoriating clinical conditions such as, cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute phase reactants and serum biochemistry in COVID\u201019. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals.In the majority of the patients, a one\u2010week, self\u2010limiting viral respiratory disease typically occurs, which ends with the development of neutralizing anti\u2010viral T cell and antibody immunity. The IgM, IgA and IgG type virus\u2010specific antibodies levels are important measurements to predict population immunity against this disease and whether cross\u2010reactivity with other coronaviruses is taking place.High viral\u2010load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID\u201019 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine\u2010secreting cells with innate and adaptive immune mechanisms both of with contribute to a poor prognosis. Elevated levels of acute phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome and novel approachs to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 49, "docid": "fczf3lzc", "rank": 76, "score": 16.941099166870117}, {"content": "Title: Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection Content: BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus\u2013reactive CD8(+) T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4(+) T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity\u2013dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8(+) T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4(+) T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8(+) T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.", "qid": 49, "docid": "98m2qy49", "rank": 77, "score": 16.909099578857422}, {"content": "Title: Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.", "qid": 49, "docid": "um9lv53e", "rank": 78, "score": 16.908998489379883}, {"content": "Title: Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity Content: Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir(1,2). Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy(3). However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8(+) T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption(4). Increased CD4(+) T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.", "qid": 49, "docid": "3vynbdli", "rank": 79, "score": 16.88759994506836}, {"content": "Title: Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection Content: Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-\u03b3. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-\u03b3 production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-\u03b3 levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines.", "qid": 49, "docid": "mbeyduzy", "rank": 80, "score": 16.876800537109375}, {"content": "Title: Passive immunization does not provide protection against experimental infection with Mycoplasma haemofelis Content: Mycoplasma haemofelis (Mhf) is the most pathogenic feline hemotropic mycoplasma. Cats infected with Mhf that clear bacteremia are protected from Mhf reinfection, but the mechanisms of protective immunity are unresolved. In the present study we investigated whether the passive transfer of antibodies from Mhf-recovered cats to na\u00efve recipient cats provided protection against bacteremia and clinical disease following homologous challenge with Mhf; moreover, we characterized the immune response in the recipient cats. Ten specified pathogen-free (SPF) cats were transfused with pooled plasma from cats that had cleared Mhf bacteremia; five control cats received plasma from na\u00efve SPF cats. After homologous challenge with Mhf, cats were monitored for 100 days using quantitative PCR, hematology, blood biochemistry, Coombs testing, flow cytometry, DnaK ELISA, and red blood cell (RBC) osmotic fragility (OF) measurement. Passively immunized cats were not protected against Mhf infection but, compared to control cats, showed significantly higher RBC OF and B lymphocyte (CD45R/B220(+)) counts and occasionally higher lymphocyte, monocyte and activated CD4(+) T lymphocyte (CD4(+)CD25(+)) counts; they also showed higher bilirubin, total protein and globulin levels compared to those of control cats. At times of peak bacteremia, a decrease in eosinophils and lymphocytes, as well as subsets thereof (B lymphocytes and CD5(+), CD4(+) and CD8(+) T lymphocytes), and an increase in monocytes were particularly significant in the passively immunized cats. In conclusion, passive immunization does not prevent bacteremia and clinical disease following homologous challenge with Mhf, but enhances RBC osmotic fragility and induces a pronounced immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0361-x) contains supplementary material, which is available to authorized users.", "qid": 49, "docid": "1uw8xcxw", "rank": 81, "score": 16.87540054321289}, {"content": "Title: Vitamin E and immune response in the aged: molecular mechanisms and clinical implications Content: Summary: Nutritional status has been indicated as a contributing factor to age\u2010related dysregulation of the immune response. Vitamin E, a lipid\u2010soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed\u2010type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)\u20102, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T\u2010cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell\u2010dividing and IL\u2010producing capacities of na\u00efve T cells, but not memory T cells. The vitamin E\u2010induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of na\u00efve T\u2010cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.", "qid": 49, "docid": "d2wru211", "rank": 82, "score": 16.853200912475586}, {"content": "Title: Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus. Content: Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1(-/-) mice lacking normal expression of activating Fc receptors (FcRgamma(-/-)) and by approximately 76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.", "qid": 49, "docid": "k9dl79kc", "rank": 83, "score": 16.835899353027344}, {"content": "Title: Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus Content: Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1\u2212/\u2212 mice lacking normal expression of activating Fc receptors (FcR\u03b3\u2212/\u2212) and by \u223c76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.", "qid": 49, "docid": "xjpev4jw", "rank": 84, "score": 16.83589744567871}, {"content": "Title: Evaluation of Burkholderia mallei \u0394tonB \u0394hcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. Content: BACKGROUND Glanders caused by Burkholderia mallei is a re-emerging zoonotic disease affecting solipeds and humans. Furthermore, B. mallei is genetically related to B. pseudomallei, which is the causative agent of melioidosis. Both facultative intracellular bacteria are classified as tier 1 select biothreat agents. Our previous study with a B. mallei \u0394tonB \u0394hcp1 (CLH001) live-attenuated vaccine demonstrated that it is attenuated, safe and protective against B. mallei wild-type strains in the susceptible BALB/c mouse model. METHODOLOGY/PRINCIPAL FINDING In our current work, we evaluated the protective efficacy of CLH001 against glanders and melioidosis in the more disease-resistant C57BL/6 mouse strain. The humoral as well as cellular immune responses were also examined. We found that CLH001-immunized mice showed 100% survival against intranasal and aerosol challenge with B. mallei ATCC 23344. Moreover, this vaccine also afforded significant cross-protection against B. pseudomallei K96243, with low level bacterial burden detected in organs. Immunization with a prime and boost regimen of CLH001 induced significantly greater levels of total and subclasses of IgG, and generated antigen-specific splenocyte production of IFN-\u03b3 and IL-17A. Interestingly, protection induced by CLH001 is primarily dependent on humoral immunity, while CD4+ and CD8+ T cells played a less critical protective role. CONCLUSIONS/SIGNIFICANCE Our data indicate that CLH001 serves as an effective live attenuated vaccine to prevent glanders and melioidosis. The quantity and quality of antibody responses as well as improving cell-mediated immune responses following vaccination need to be further investigated prior to advancement to preclinical studies.", "qid": 49, "docid": "ube8ytcp", "rank": 85, "score": 16.793399810791016}, {"content": "Title: Immunologic characterization of a immunosuppressed multiple sclerosis patient that recovered from SARS-CoV-2 infection Content: A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after discontinuation.", "qid": 49, "docid": "03dzqten", "rank": 86, "score": 16.76919937133789}, {"content": "Title: Immunologic characterization of a immunosuppressed multiple sclerosis patient that recovered from SARS-CoV-2 infection Content: A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after drug discontinuation.", "qid": 49, "docid": "5mk4jcn6", "rank": 87, "score": 16.769197463989258}, {"content": "Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections Content: In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.", "qid": 49, "docid": "njaw5mra", "rank": 88, "score": 16.765199661254883}, {"content": "Title: Single-cell RNA-seq and V(D)J profiling of immune cells in COVID-19 patients Content: Coronavirus disease 2019 (COVID-19) has caused over 220,000 deaths so far and is still an ongoing global health problem. However, the immunopathological changes of key types of immune cells during and after virus infection remain unclear. Here, we enriched CD3+ and CD19+ lymphocytes from peripheral blood mononuclear cells of COVID-19 patients (severe patients and recovered patients at early or late stages) and healthy people (SARS-CoV-2 negative) and revealed transcriptional profiles and changes in these lymphocytes by comprehensive single-cell transcriptome and V(D)J recombination analyses. We found that although the T lymphocytes were decreased in the blood of patients with virus infection, the remaining T cells still highly expressed inflammatory genes and persisted for a while after recovery in patients. We also observed the potential transition from effector CD8 T cells to central memory T cells in recovered patients at the late stage. Among B lymphocytes, we analyzed the expansion trajectory of a subtype of plasma cells in severe COVID-19 patients and traced the source as atypical memory B cells (AMBCs). Additional BCR and TCR analyses revealed a high level of clonal expansion in patients with severe COVID-19, especially of B lymphocytes, and the clonally expanded B cells highly expressed genes related to inflammatory responses and lymphocyte activation. V-J gene usage and clonal types of higher frequency in COVID-19 patients were also summarized. Taken together, our results provide crucial insights into the immune response against patients with severe COVID-19 and recovered patients and valuable information for the development of vaccines and therapeutic strategies.", "qid": 49, "docid": "yrfcqf4b", "rank": 89, "score": 16.744400024414062}, {"content": "Title: Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection Content: Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable.", "qid": 49, "docid": "m7nij17v", "rank": 90, "score": 16.716899871826172}, {"content": "Title: Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development Content: Heterologous immunity (H.I.) is a consequence of an encounter with a specific antigen, which can alter the subsequent immune response to a different antigen. This can happen at the innate immune system level\u2014often called trained immunity or innate immune memory\u2014and/or at the adaptive immune system level involving T memory cells and antibodies. Viruses may also induce T cell-mediated H.I., which can confer protection or drive immunopathology against other virus subtypes, related or unrelated viruses, other pathogens, auto- or allo-antigens. It is important to understand the underlying mechanisms for the development of antiviral \u201cuniversal\u201d vaccines and broader T cell responses rather than just subtype-specific antibody responses as in the case of influenza. Furthermore, knowledge about determinants of vaccine-mediated H.I. may inform public health policies and provide suggestions for repurposing existing vaccines. Here, we introduce H.I. and provide an overview of evidence on virus- and antiviral vaccine-induced T cell-mediated cross-reactive responses. We also discuss the factors influencing final clinical outcome of virus-mediated H.I. as well as non-specific beneficial effects of live attenuated antiviral vaccines such as measles and vaccinia. Available epidemiological and mechanistic data have implications both for the development of new vaccines and for personalized vaccinology, which are presented. Finally, we formulate future research priorities and opportunities.", "qid": 49, "docid": "hotxaou2", "rank": 91, "score": 16.710500717163086}, {"content": "Title: Lactate dehydrogenase-elevating virus: an ideal persistent virus? Content: LDV contradicts all commonly held views about mechanisms of virus persistence, namely that persistence is primarily associated with noncytopathic viruses, or the selection of immune escape variants or other mutants, or a decrease in expression of certain viral proteins by infected cells, or replication in \u201cimmune-privileged sites\u201d, or a general suppression of the host immune system, etc. [1, 2, 5, 54, 77, 78]. LDV is a highly cytocidal virus that invariably establishes a life-long, viremic, persistence in mice, in spite of normal anti-viral immune responses. One secret of LDV's success in persistence is its specificity for a renewable, nonessential population of cells that is continuously regenerated, namely a subpopulation of macrophages. Since the continuous destruction of these cells is not associated with any obvious health effects, this macrophage population seems nonessential to the well-being of its host. The only function identified for this subpopulation of macrophages is clearance of the muscle type of LDH and some other enzymes [59, 67, 68]. Furthermore, the effects of LDV infection on the host immune system, namely the polyclonal activation of B cells and its associated production of autoantibodies, and the slight impairment of primary and secondary antibody responses also do not seem to be severe enough to cause any clinical consequences. But how does LDV replication in macrophages escape all host defenses? Persistence is not dependent on the seletion of immune escape variants or other mutants ([58] and Palmer, Even and Plagemann, unpublished results). Also, LDV replication is not restricted to immune-privileged sites [5]. LDV replication persists in the liver, lymphoidal tissues and testis [66]. Only the latter could be considered a site not readily accessible to immune surveillance. Most likely, resistance of LDV replication to antiviral immune responses is related to the unique structure of its envelope proteins and the production of large quantities of viral antigens. High titers of anti-LDV antibodies are generated in infected mice but they neutralize LDV infectivity only very inefficiently and, even though the antiviral antibodies are mainly of the IgG2a and IgG2b isotypes, they do not mediate complement lyses of virions [31]. Interaction of the antibodies and complement with the VP-3/VP-2 heterodimers in the viral envelope may be impeded by the exposure of only very short peptide segments of these proteins at the envelope surface and the presence of large oligosaccharide side chains. Furthermore, since LDV maturation is restricted to intracytoplasmic cisternae [59, 71], the question arises of whether any of the viral proteins are available on the surface of infected cells for ADCC. CTLs also fail to control LDV replication. Altough CTLs specific for N/VP-1 are rapidly generated, these have disappeared by 30 days p.i. [26]. The reasons for this loss are unknown, but high-dose clonal exhaustion [41, 51, 77, 78] is a reasonable possibility since, regardless of the infectious dose, large amounts of LDV proteins are present in all the lymphoidal tissues at the time of the induction of the CTL response. Furthermore, after exhaustion of CTLs in the periphery, continuous replication of LDV in the thymus [65] assures that the mice become permanently immunologically tolerant with respect to LDV antigen-specific CTLs as a result of negative selection in the thymus. LDV might be a primary example for the effectiveness of a permanent clonal CTL deletion in adult animals under natural conditions of infection. The presumed modes of transmission of LDV in nature and the events associated with its infection of mice are strikingly similar to those observed during the acute and asymptomatic phases of infection with human immunodeficiency virus (HIV) [24, 29, 74, 78]. These include: (1) primary inefficient transmission via sexual and transplacental routes but effective transmission via blood; (2) primary replication in renewable populations of lymphoidal cells with production of large amounts of virus after the initial infection of the host followed by persistent low level of viremia in spite of antiviral immune responses; (3) persistence, reflecting continuous rounds of productive, cytocidal infection of permissive cells [59, 74] and the rate of generation of permissive cells which may be the main factor in determining the level of virus production (in the case of HIV, the rate of activation of CD4(+) T cells to support a productive HIV replication might be the factor determining the rate of virus production and the progression of the disease); (4) rapid antibody formation but delayed production of neutralizing antibodies with limited neutralizing capacity; (5) rapid but transient generation of virus-specific CTLs; and (6) accumulation of large amounts of virus in newly formed germinal centers in the spleen and lymph nodes concomitant with an initiation of a permanent polyclonal activation of B cells resulting in an elevation of plasma IgG2a. The events described under points 2\u20136 might be generally associated with natural viremic persistent virus infections. Such persistent viruses, by necessity, have evolved properties that allow them to escape all host defenses and control of their infection by immunological processes is, therefore, difficult, if not impossible. Prevention of infection and chemotherapy may be the only approaches available to combat such virus infections.", "qid": 49, "docid": "5ka9909n", "rank": 92, "score": 16.70560073852539}, {"content": "Title: Heterologous immunity between viruses. Content: Immune memory responses to previously encountered pathogens can sometimes alter the immune response to and the course of infection of an unrelated pathogen by a process known as heterologous immunity. This response can lead to enhanced or diminished protective immunity and altered immunopathology. Here, we discuss the nature of T-cell cross-reactivity and describe matrices of epitopes from different viruses eliciting cross-reactive CD8(+) T-cell responses. We examine the parameters of heterologous immunity mediated by these cross-reactive T cells during viral infections in mice and humans. We show that heterologous immunity can disrupt T-cell memory pools, alter the complexity of the T-cell repertoire, change patterns of T-cell immunodominance, lead to the selection of viral epitope-escape variants, alter the pathogenesis of viral infections, and, by virtue of the private specificity of T-cell repertoires within individuals, contribute to dramatic variations in viral disease. We propose that heterologous immunity is an important factor in resistance to and variations of human viral infections and that issues of heterologous immunity should be considered in the design of vaccines.", "qid": 49, "docid": "v3q9tvyv", "rank": 93, "score": 16.693700790405273}, {"content": "Title: Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE Content: Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FC\u03b3RIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(\u2212/\u2212)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(\u2212/\u2212) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFN\u03b3 in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 (\u2212/\u2212) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP(33) and NP(396) were detected within the liver of fgl2(\u2212/\u2212) mice. Plasma from fgl2(\u2212/\u2212) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(\u2212/\u2212) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.", "qid": 49, "docid": "e10gvk0h", "rank": 94, "score": 16.68549919128418}, {"content": "Title: A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy Content: Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCas(E) murine retrovirus on day 8 after birth die of leukemia within 4\u20135 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through Fc\u03b3R-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies.", "qid": 49, "docid": "6co97g5p", "rank": 95, "score": 16.586700439453125}, {"content": "Title: Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults Content: Abstract Objectives Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60\u201375 years. Methods We evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra-muscular (IM) injection (n = 6), two doses of IM PanAd3-RSV given 4-weeks apart (n = 6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), or no vaccine (n = 6). Safety measures included all adverse events within one week of vaccination and blood monitoring. Immunogenicity measures included serum antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation and SEAP assays, respectively), peripheral B-cell immune responses (frequencies of F-specific IgG and IgA antibody secreting cells and memory B-cells by ex vivo and cultured dual-colour ELISpot assays respectively), and peripheral RSV-specific T-cell immune responses (frequencies of IFN\u03b3-producing T-cells by ex vivo ELISpot and CD4+/CD8+/Tfh-like cell frequencies by ICS/FACS assay). Results The vaccines were safe and well tolerated. Compared with each individual baseline immunity the mean fold-changes in serum RSV-neutralising antibody, appearance and magnitude of F-specific IgG and IgA ASCs and expansion of CD4+/CD8+ IFN\u03b3-producing T-cells in peripheral circulation were comparable to the results seen from younger healthy adults who received the same vaccine combination and dose. There were little/no IgA memory B-cell responses in younger and older adults. Expansion of IFN\u03b3-producing T-cells was most marked in older adults following IM prime, with balanced CD4+ and CD8+ T cell responses. The RSV-specific immune responses to vaccination did not appear to be attenuated in the presence of PanAd3 (vector) neutralising antibody. Conclusions PanAd3-RSV and MVA-RSV was safe and immunogenic in older adults and the parallel induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.", "qid": 49, "docid": "zbc6tbdc", "rank": 96, "score": 16.5802001953125}, {"content": "Title: Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice with Alphavirus Encephalomyelitis. Content: UNLABELLED Inflammation is a necessary part of the response to infection but can also cause neuronal injury in both infectious and autoimmune diseases of the central nervous system (CNS). A neurovirulent strain of Sindbis virus (NSV) causes fatal paralysis in adult C57BL/6 mice during clearance of infectious virus from the CNS, and the virus-specific immune response is implicated as a mediator of neuronal damage. Previous studies have shown that survival is improved in T-cell-deficient mice and in mice with pharmacological inhibition of the inflammatory response and glutamate excitotoxicity. Because glutamine metabolism is important in the CNS for the generation of glutamate and in the immune system for lymphocyte proliferation, we tested the effect of the glutamine antagonist DON (6-diazo-5-oxo-l-norleucine) on the outcome of NSV infection in mice. DON treatment for 7 days from the time of infection delayed the onset of paralysis and death. Protection was associated with reduced lymphocyte proliferation in the draining cervical lymph nodes, decreased leukocyte infiltration into the CNS, lower levels of inflammatory cytokines, and delayed viral clearance. In vitro studies showed that DON inhibited stimulus-induced proliferation of lymphocytes. When in vivo treatment with DON was stopped, paralytic disease developed along with the inflammatory response and viral clearance. These studies show that fatal NSV-induced encephalomyelitis is immune mediated and that antagonists of glutamine metabolism can modulate the immune response and protect against virus-induced neuroinflammatory disease. IMPORTANCE Encephalomyelitis due to infection with mosquito-borne alphaviruses is an important cause of death and of long-term neurological disability in those who survive infection. This study demonstrates the role of the virus-induced immune response in the generation of neurological disease. DON, a glutamine antagonist, inhibited the proliferation of lymphocytes in response to infection, prevented the development of brain inflammation, and protected mice from paralysis and death during treatment. However, because DON inhibited the immune response to infection, clearance of the virus from the brain was also prevented. When treatment was stopped, the immune response was generated, brain inflammation occurred, virus was cleared, and mice developed paralysis and died. Therefore, more definitive treatment for alphaviral encephalomyelitis should inhibit virus replication as well as neuroinflammatory damage.", "qid": 49, "docid": "9a058w8d", "rank": 97, "score": 16.568899154663086}, {"content": "Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 49, "docid": "rs79r7kc", "rank": 98, "score": 16.529800415039062}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 49, "docid": "rsz7ch2a", "rank": 99, "score": 16.52979850769043}, {"content": "Title: Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection Content: Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation. One Sentence Summary Broad immune perturbations in severe COVID-19", "qid": 49, "docid": "mdsjbfmx", "rank": 100, "score": 16.479799270629883}]}
{"query": "what is known about an mRNA vaccine for the SARS-CoV-2 virus?", "hits": [{"content": "Title: An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development Content: The first outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province, China, in late 2019. The subsequent COVID-19 pandemic rapidly affected the health and economy of the world. The global approach to the pandemic was to isolate populations to reduce the spread of this deadly virus while vaccines began to be developed. In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). The production of mRNA-based vaccines is a promising recent development in the production of vaccines. However, there remain significant challenges in the development and testing of vaccines as rapidly as possible to control COVID-19, which requires international collaboration. This review aims to describe the background to the rationale for the development of mRNA-based SARS-CoV-2 vaccines and the current status of the mRNA-1273 vaccine.", "qid": 50, "docid": "xbze5s3c", "rank": 1, "score": 11.555299758911133}, {"content": "Title: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Content: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining", "qid": 50, "docid": "3wuh6k6g", "rank": 2, "score": 11.18850040435791}, {"content": "Title: Current Therapies Under Investigation for COVID-19 Content: In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This mini-review also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV.", "qid": 50, "docid": "050fdtm8", "rank": 3, "score": 11.070099830627441}, {"content": "Title: Current Therapies Under Investigation for COVID-19. Content: In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This mini-review also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV.", "qid": 50, "docid": "u3xxshqw", "rank": 4, "score": 11.070098876953125}, {"content": "Title: M\u00f6gliche Therapiestrategien bei Covid-19-Erkrankungen mit chinesischen Arzneimitteln Content: In view of the severe corona virus pandemic and the not yet foreseeable availability of causal therapy approaches (vaccination, antiviral drugs), it is of great importance to know what Chinese medicine can contribute to the treatment of Covid 19. According to a WHO report published in 2004, concerning the 2003 SARS epidemic caused by SARS-CoV-1, Chinese medicine was used in China both preventively and therapeutically in addition to Western medicine. In both these preventive and curative roles, treatment proved to be significantly effective. During the current outbreak of SARS-CoV-2, about 60,000 Covid 19 patients were treated with Chinese medicine in the Wuhan region alone by the end of February 2020. The first part of this paper provides a summarizing overview of a number of sources with treatment recommendations and experiences of different clinics, working groups and official bodies. In the second part - based on currently known information \u2014 the author voices his own considerations on pathophysiology and important therapeutic principles. Finally, he presents preliminary treatment proposals using Chinese medicinal remedies for what appear to be the central pattern of the disorder - a blockage of pulmonary qi and the transformation of fluids in the context of an accumulation of dampness /humor with toxicity and, in severe cases, development into pneumonia.", "qid": 50, "docid": "pb3r74uq", "rank": 5, "score": 11.053000450134277}, {"content": "Title: Coronaviruses: important emerging human pathogens. Content: The identification of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 reaffirmed the importance of understanding how coronaviruses emerge, infect, and cause disease. By comparing what is known about severe acute respiratory syndrome coronavirus (SARS-CoV) to what has recently been found for MERS-CoV, researchers are discovering similarities and differences that may be important for pathogenesis. Here we discuss what is known about each virus and what gaps remain in our understanding, especially concerning MERS-CoV.", "qid": 50, "docid": "inxp2qb4", "rank": 6, "score": 10.927800178527832}, {"content": "Title: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes Content: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it\u2019s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven\u2019t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don\u2019t yet know what the real-life significance of this variation is, but it\u2019s possible that these variants decrease the protein\u2019s ability to interact with the SARS-CoV-2 virus, thus decreasing the person\u2019s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.", "qid": 50, "docid": "p7drekee", "rank": 7, "score": 10.917400360107422}, {"content": "Title: Coronavirus SARS-CoV-2: Analysis of subgenomic mRNA transcription, 3CLpro and PL2pro protease cleavage sites and protein synthesis Content: Coronaviruses have recently caused world-wide severe outbreaks: SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle-East Respiratory Syndrome) in 2012. At the end of 2019, a new coronavirus outbreak appeared in Wuhan (China) seafood market as first focus of infection, becoming a pandemics in 2020, spreading mainly into Europe and Asia. Although the virus family is well-known, this specific virus presents considerable differences, as higher transmission rates, being a challenge for diagnostic methods, treatments and vaccines. Coronavirus.pro is a C++ application which simulates Coronavirus replication cycle. This software has identified virus type in short times and provided FASTA files of virus proteins, a list of mRNA sequences and secondary structures. Furthermore, the software has identified a list of structural, non-structural and accessory proteins in 2019-nCoV virus genome more similar to SARS than to MERS, as several fusion proteins characteristics of this virus type. These results are useful as a first step in order to develop diagnostic methods, new vaccines or antiviral drugs, which could avoid virus replication in any stage: fusion inhibitors, RdRp inhibitors and PL2pro/3CLpro protease inhibitors.", "qid": 50, "docid": "ll76vrr3", "rank": 8, "score": 10.896300315856934}, {"content": "Title: On the evolutionary epidemiology of SARS-CoV-2 Content: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.", "qid": 50, "docid": "ig0rnbqb", "rank": 9, "score": 10.828399658203125}, {"content": "Title: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. Content: SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.", "qid": 50, "docid": "ipw96f03", "rank": 10, "score": 10.791999816894531}, {"content": "Title: Search for SARS-CoV-2 inhibitors in currently approved drugs to tackle COVID-19 pandemia Content: Different treatments are currently used for clinical management of SARS-CoV-2 infection, but little is known about their efficacy yet. Here we present ongoing results to compare currently available drugs for a variety of diseases to find out if they counteract SARS-CoV-2-induced cytopathic effect in vitro. Our goal is to prioritize antiviral activity to provide a solid evidence-driven rationale for forthcoming clinical trials. Since the most effective antiviral approaches are usually based on combined therapies that tackle the viral life cycle at different stages, we are also testing combinations of drugs that may be critical to reduce the emergence of resistant viruses. We will provide results as soon as they become available, so data should be interpreted with caution, clearly understanding the limitations of the in vitro model, that may not always reflect what could happen in vivo. Thus, our goal is to test the most active antivirals identified in adequate animal models infected with SARS-CoV-2, to add more information about possible in vivo efficacy. In turn, successful antivirals could be tested in clinical trials as treatments for infected patients, but also as pre-exposure prophylaxis to avoid novel infections until an effective and safe vaccine is developed.", "qid": 50, "docid": "ywaefpe8", "rank": 11, "score": 10.776599884033203}, {"content": "Title: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection Content: SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2\u00e2\u0080\u008a114\u00e2\u0080\u008a269 people, resulting in 145\u00e2\u0080\u008a144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.", "qid": 50, "docid": "fzdmcahf", "rank": 12, "score": 10.758899688720703}, {"content": "Title: Adding the missing sugars to coronavirus protein structures Content: Protein structures solved by cryo-electron microscopy (cryo-EM) or X-ray crystallography often miss the sugar molecules known as glycans that cover large swaths of the proteins\u2019 surfaces The recently reported structures of the spike protein on SARS-CoV-2, the novel coronavirus that causes COVID-19, are no different Researchers are now working to fill in some of those sugary blanks to better understand the virus\u2019s biology and to help drugmakers develop vaccines and treatments \u201cPeople usually go for what they can analyze\u201d and focus mostly on the protein components of a structure, says Andrea Thorn, a structural biologist at the Julius Maximilian University of W\u00fcrzburg She is a member of the Coronavirus Structural Task Force, a group of scientists who specialize in modeling and processing crystallographic and cryo-EM data Because structural biology measurements don\u2019t reveal much about glycans on proteins, \u201cwe often fail to recognize what an important part of the structure they", "qid": 50, "docid": "fayr38c7", "rank": 13, "score": 10.71500015258789}, {"content": "Title: Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach Content: SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.", "qid": 50, "docid": "q77da2y3", "rank": 14, "score": 10.665300369262695}, {"content": "Title: SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness Content: A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.", "qid": 50, "docid": "1v0f2dtx", "rank": 15, "score": 10.548600196838379}, {"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen with Potential Fecal-Oral Transmission: A COVID-19 Virological and Clinical Review Content: Abstract In as short as 3 months, COVID-19 has spread and ravaged the world in an unprecedented speed in modern history rivaling the 1918 flu pandemic. SARS-CoV-2, the culprit virus, is highly contagious and stable in the environment and predominantly transmits among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that SARS-CoV-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 50, "docid": "9rg9xe57", "rank": 16, "score": 10.537400245666504}, {"content": "Title: SARS\u2010CoV\u20102: what is known and what there is to know. Focus on coagulation and lipids Content: As the SARS\u2010CoV2 pandemic is still progressing, dissemination of information has become of paramount importance. However, the rapid influx of SARS\u2010CoV\u20102 patients in our hospitals has overwhelmed the time needed for appropriate information interpretation and its application. Noteworthy, awareness among clinicians is growing about the systemic involvement triggered by SARS\u2010CoV\u20102 infection. Here we focused on two emerging clinical feature associated with SARS\u2010CoV\u20102 infection with potential long\u2010term relevance.", "qid": 50, "docid": "cyopezdr", "rank": 17, "score": 10.44909954071045}, {"content": "Title: Implications of the virus-encoded miRNA and host miRNA in the pathogenicity of SARS-CoV-2 Content: The outbreak of COVID-19 caused by SARS-CoV-2 has rapidly spread worldwide and has caused over 1,400,000 infections and 80,000 deaths. There are currently no drugs or vaccines with proven efficacy for its prevention and little knowledge was known about the pathogenicity mechanism of SARS-CoV-2 infection. Previous studies showed both virus and host-derived MicroRNAs (miRNAs) played crucial roles in the pathology of virus infection. In this study, we use computational approaches to scan the SARS-CoV-2 genome for putative miRNAs and predict the virus miRNA targets on virus and human genome as well as the host miRNAs targets on virus genome. Furthermore, we explore miRNAs involved dysregulation caused by the virus infection. Our results implicated that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Impressively, we found hsa-miR-4661-3p was predicted to target the S gene of SARS-CoV-2, and a virus-encoded miRNA MR147-3p could enhance the expression of TMPRSS2 with the function of strengthening SARS-CoV-2 infection in the gut. The study may provide important clues for the mechisms of pathogenesis of SARS-CoV-2.", "qid": 50, "docid": "nk0wie0w", "rank": 18, "score": 10.413299560546875}, {"content": "Title: A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.", "qid": 50, "docid": "ptvsie6m", "rank": 19, "score": 10.396400451660156}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 50, "docid": "41378qru", "rank": 20, "score": 10.373100280761719}, {"content": "Title: COVID\u201019 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS\u2010CoV\u20102, causative agent of COVID\u201019, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID\u201019. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS\u2010CoV\u20102 and discuss the evidence and explications for a disproportionately stronger impact of COVID\u201019 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS\u2010CoV\u20102 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS\u2010CoV\u20102.", "qid": 50, "docid": "ipl6189w", "rank": 21, "score": 10.373099327087402}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of COVID-19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 50, "docid": "l2wzr3w1", "rank": 22, "score": 10.373098373413086}, {"content": "Title: [What is the origin of SARS-CoV-2?] Content: Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.", "qid": 50, "docid": "dv9m19yk", "rank": 23, "score": 10.36240005493164}, {"content": "Title: Point-of-care lung ultrasound in three neonates with COVID-19 Content: Since March 2020, the world is involved in the COVID-19 pandemic, a disease caused by a novel virus called SARS-CoV-2. Some authors have described the ultrasonographic findings of COVID-19 pneumonia in adults and children, but data on neonates are lacking. Our objective was to describe the ultrasonographic lung pattern on newborns with SARS-CoV-2 infection during the COVID-19 pandemic. Newborns who tested positive for SARS-CoV-2 PCR in respiratory samples and were evaluated with point-of-care lung ultrasound (LU) from March to April 2020 were included. LU was performed bedside by a single investigator at the time of diagnosis and every 48 h during the first week following diagnosis. Six areas were studied. Three neonates were included. Infants' comorbidities included meconium aspiration syndrome, bronchopulmonary dysplasia, and Hirschsprung's disease. One required mechanical ventilation. No deaths occurred. LU showed B-lines, consolidation, and spared areas. No pneumothorax or pleural effusion was observedConclusions: LU could be of value when managing COVID-19 neonates. We describe the findings of lung ultrasound monitoring during the first week following diagnosis in three neonates with SARS-CoV-2 infection. What is known: \u00e2\u0080\u00a2 Lung ultrasound (LU) is a useful tool in COVID-19 management in adults. To date, no report on LU and neonates with SARS-CoV-2 infection has been published. What is new: \u00e2\u0080\u00a2 This study adds evidence about LU findings in neonates with SARS-CoV-2 infection.", "qid": 50, "docid": "pab56xyd", "rank": 24, "score": 10.361599922180176}, {"content": "Title: Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo Content: SARS-CoV-2 has rapidly become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. Here, we systematically investigated the untranslated regions (UTRs) of mRNAs in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, we identified the optimal combination of 5\u2019 and 3\u2019 UTR, termed as NASAR, which was five to ten-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived nanoparticles showed dramatic expression of potential SARS-CoV-2 antigens both in vitro and in vivo. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.", "qid": 50, "docid": "aju2nr9x", "rank": 25, "score": 10.361100196838379}, {"content": "Title: Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-\u03baB signaling pathway Content: Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host\u2019s immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-\u03baB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-\u03baB p65, p-I\u03baB\u03b1 and p-p38 MAPK, while increasing the expression of I\u03baB\u03b1. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-\u03baB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.", "qid": 50, "docid": "xg8tmibr", "rank": 26, "score": 10.306699752807617}, {"content": "Title: Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2) Content: About 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS coronavirus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. All coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshift (-1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have revealed that it employs a structurally unique three-stemmed mRNA pseudoknot that stimulates high -1 PRF rates and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity impairs virus replication, suggesting that this activity may be therapeutically targeted. Here, we comparatively analyzed the SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar -1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate -1 PRF activity. We noted that the upstream attenuator hairpin activity is also functionally retained in both viruses, despite differences in the primary sequence in this region. Small-angle X-ray scattering analyses indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 have the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.", "qid": 50, "docid": "mk7992xk", "rank": 27, "score": 10.297300338745117}, {"content": "Title: Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2). Content: About 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS coronavirus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. All coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshift (-1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have revealed that it employs a structurally unique three-stemmed mRNA pseudoknot that stimulates high -1 PRF rates and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity impairs virus replication, suggesting that this activity may be therapeutically targeted. Here, we comparatively analyzed the SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar -1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate -1 PRF activity. We noted that the upstream attenuator hairpin activity is also functionally retained in both viruses, despite differences in the primary sequence in this region. Small-angle X-ray scattering analyses indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 have the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.", "qid": 50, "docid": "yxiacesg", "rank": 28, "score": 10.2972993850708}, {"content": "Title: Molecular targets for COVID-19 drug development: Enlightening Nigerians about the pandemic and future treatment Content: There is little or no research initiated on enlightening Nigerians about the pathogenesis, targets for drug development, and drug repositioning for SARS-CoV-2 infection. COVID-19 is a viral infection causing symptoms like dry cough, sore throat, nasal congestion, tiredness, fever, loss of taste and smell etc. Th disease was first reported in Wuhan, China, in December 2019. The infection is caused by SARS-CoV-2, which is the third introduction of a highly pathogenic coronavirus into the human population. Coronaviruses are viruses with a positive RNA envelope assigned to \u03b1, \u03b2, \u03b3, and \u03b4 genera. Moreover, SARS-CoV-2 belongs to the \u03b2 genus. The four structural proteins of \u03b2 coronavirus are membrane (M), envelope (E), spike (S), and nucleocapsid (N) protein, mediation of coronavirus host infection is established by spike (S) protein. Therefore, the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic. It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor, viral RNA synthesis and replication, 3CLpro, RdRp, and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection. Furthermore, the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development. Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19, and mRNA-1273 targeting spike protein is the promising vaccine. However, as patient management and drug repositioning are taking place, it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection, to develop novel therapeutics.", "qid": 50, "docid": "ddt5qmls", "rank": 29, "score": 10.27810001373291}, {"content": "Title: ACE-inibitori, sartani e sindrome respiratoria acuta da coronavirus 2./ [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus] Content: Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.", "qid": 50, "docid": "mi0pmyo4", "rank": 30, "score": 10.262800216674805}, {"content": "Title: [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus]. Content: Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.", "qid": 50, "docid": "mclozg5p", "rank": 31, "score": 10.237899780273438}, {"content": "Title: COVID-19 vaccines: Knowing the unknown Content: Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain - some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.", "qid": 50, "docid": "hotn7qha", "rank": 32, "score": 10.225899696350098}, {"content": "Title: COVID\u201019 vaccines: knowing the unknown Content: Vaccine development against SARS\u2010CoV\u20102 has drawn attention around the globe due to the exploding pandemic. Although COVID\u201019 is caused by a new coronavirus, SARS\u2010CoV\u20102, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID\u201019 vaccine. However, important knowledge gaps remain \u2013 some are specific to SARS\u2010CoV\u20102, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID\u201019 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID\u201019 has been remarkable. We are therefore optimistic about the rapid development of COVID\u201019 vaccine. This article is protected by copyright. All rights reserved", "qid": 50, "docid": "tdvb0fhv", "rank": 33, "score": 10.225898742675781}, {"content": "Title: Children and SARS-CoV-2 infection: innocent bystanders\u2026until proven otherwise Content: In this commentary, we focus our attention on what is known about SARS-CoV-2 infection in the pediatric population. We report literature and National data. The possible and different explanations for understanding why the infection seems to be more benign and less frequent in children are discussed. The possible role of children in the COVID-19 viral disease pandemic is also commented. Finally, our work suggests to search for future evidence and containment strategies to manage virus spread.", "qid": 50, "docid": "5gio6ruj", "rank": 34, "score": 10.204000473022461}, {"content": "Title: Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-\u03baB signaling pathway Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-&#945;, IL-6, IL-1\u00df, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-&#954;B/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-&#954;B p65, p-I&#954;B&#945; and p-p38 MAPK, while increasing the expression of I&#954;B&#945;. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-&#954;B/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.", "qid": 50, "docid": "ir5mv8q0", "rank": 35, "score": 10.185700416564941}, {"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 50, "docid": "khfiy0m2", "rank": 36, "score": 10.171600341796875}, {"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds. Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 50, "docid": "y883anmp", "rank": 37, "score": 10.171599388122559}, {"content": "Title: Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin. Content: UNLABELLED The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic human CoVs that share a property to inhibit host gene expression at the posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS-CoV that inhibits host gene expression at the translational level, we report that MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene expression by inhibiting host mRNA translation and inducing the degradation of host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of MERS-CoV nsp1, most probably triggered by its ability to induce an endonucleolytic RNA cleavage, was separable from its translation inhibitory function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly different strategy that selectively targeted translationally competent host mRNAs for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV nsp1 was distributed in both the nucleus and the cytoplasm and did not bind stably to the 40S subunit, suggesting a distinctly different mode of targeting translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1 selectively targeted mRNAs, which are transcribed in the nucleus and transported to the cytoplasm, for translation inhibition and mRNA degradation but spared exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that originate in the cytoplasm. Collectively, these data point toward a novel viral strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their escape from the inhibitory effects of MERS-CoV nsp1. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human CoV that emerged in Saudi Arabia in 2012. MERS-CoV has a zoonotic origin and poses a major threat to public health. However, little is known about the viral factors contributing to the high virulence of MERS-CoV. Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors. The nonstructural protein 1 (nsp1) of CoVs is one such protein that inhibits host gene expression and is a major virulence factor. This study presents evidence for a strategy used by MERS-CoV nsp1 to inhibit host gene expression that has not been described previously for any viral protein. The present study represents a meaningful step toward a better understanding of the factors and molecular mechanisms governing the virulence and pathogenesis of MERS-CoV.", "qid": 50, "docid": "xeu35i0n", "rank": 38, "score": 10.159700393676758}, {"content": "Title: Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Content: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002\u20132003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients\u2019 sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "qid": 50, "docid": "dqour5jr", "rank": 39, "score": 10.084500312805176}, {"content": "Title: Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Content: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "qid": 50, "docid": "dtwstwbe", "rank": 40, "score": 10.08449935913086}, {"content": "Title: A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Content: The possibility of antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection have the theoretical potential to amplify viral infections or trigger immunopathology. Observations relevant to the risks of ADE of disease require careful review at this critical point in the SARS-CoV-2 pandemic. At present, no clinical findings, immunologic assays or biomarkers are known to differentiate any severe viral infection from immune-enhanced disease, whether by antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same, and designing animal models depends on understanding how antiviral host responses may become harmful in people. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, since we cannot predict ADE of disease reliably after either vaccination or treatment with antibodies, regardless of what virus is the causative agent, it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 disease move forward.", "qid": 50, "docid": "x73moqog", "rank": 41, "score": 10.063199996948242}, {"content": "Title: Another Set of Coronavirus Vaccine Candidates Content: I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting) Now it\u2019s time to look at several programs that aren\u2019t in either of those, but still have plenty of serious science behind them For an example of a relatively new technology that\u2019s now in use for human patients, there\u2019s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck Stat has an excellent long-form article from earlier this year about how this came about, and it\u2019s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they\u2019re using those lessons in their current work If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors \u2013 this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses I don\u2019t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2 These projects are aiming at FDA approval for Phase I trials, but there\u2019s no word yet on what such an application might go in", "qid": 50, "docid": "zwf26o63", "rank": 42, "score": 10.047599792480469}, {"content": "Title: The EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) initiative: background and protocol for the international SARS-CoV-2 infections registry Content: The outbreak of SARS-CoV-2 is the worst healthcare emergency of this century, and its impact on pediatrics and neonatology is still largely unknown. The European Society for Pediatric and Neonatal Intensive Care (ESPNIC) launched the EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) international, multicenter, and multidisciplinary initiative to study the epidemiology, clinical course, and outcomes of pediatric and neonatal SARS-CoV-2 infections. EPICENTRE background and aims are presented together with protocol details. EPICENTRE is open to centers all over the world, and this will allow to provide a pragmatic picture of the epidemic, with a particular attention to pediatric and neonatal critical care issues.Conclusions: EPICENTRE will allow researchers to clarify the epidemiology, clinical presentation, and outcomes of pediatric and neonatal SARS-CoV-2 infection, refining its clinical management and hopefully providing new insights for clinicians. What is Known: \u00e2\u0080\u00a2 COVID19 is the new disease caused by SARS-CoV-2 infection and is spreading around the globe. \u00e2\u0080\u00a2 Majority of data available about SARS-CoV-2 infections originates from adult patients. What is New: \u00e2\u0080\u00a2 EPICENTRE is the first international, multicenter, multidisciplinary, meta-data driven, hospital-based, online, prospective cohort registry dedicated to neonatal and pediatric SARS-CoV-2 infections. \u00e2\u0080\u00a2 EPICENTRE will allow to understand epidemiology and physiopathology of COVID19.", "qid": 50, "docid": "pzf6a26k", "rank": 43, "score": 9.95009994506836}, {"content": "Title: What orthopedic surgeons need to know about Covid-19 pandemic Content: The ongoing outbreak of COVID-19, also known as SARS-CoV-2 and coronavirus disease 2019, is considered a major public concern that propagates steadily by the increased number of the infected cases and the mortality rate. In this article, we provide a brief review for Orthopedic surgeons as regard COVID-19 virus microbiology, epidemiology, clinical picture, and diagnosis. Moreover, what measures should be taken amid this pandemic to assess its control, maintain the urgent duties, and protect health care workers (HCW) are also discussed.", "qid": 50, "docid": "9pmix2zq", "rank": 44, "score": 9.869199752807617}, {"content": "Title: What orthopedic surgeons need to know about Covid-19 pandemic() Content: The ongoing outbreak of COVID-19, also known as SARS-CoV-2 and coronavirus disease 2019, is considered a major public concern that propagates steadily by the increased number of the infected cases and the mortality rate. In this article, we provide a brief review for Orthopedic surgeons as regard COVID-19 virus microbiology, epidemiology, clinical picture, and diagnosis. Moreover, what measures should be taken amid this pandemic to assess its control, maintain the urgent duties, and protect health care workers (HCW) are also discussed.", "qid": 50, "docid": "bbnbnwte", "rank": 45, "score": 9.8691987991333}, {"content": "Title: Rapid development of an inactivated vaccine for SARS-CoV-2 Content: The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3\u03bcg or 6 \u03bcg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence Summary A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology", "qid": 50, "docid": "m1bvurwi", "rank": 46, "score": 9.815999984741211}, {"content": "Title: Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway Content: Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, are enveloped RNA viruses that carry a large positive-sense single-stranded RNA genome and cause a variety of diseases in humans and domestic animals. Very little is known about the host pathways that regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense-mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs harboring aberrant features and targets them for degradation. Although CoV mRNAs are of cytoplasmic origin, the presence of several NMD-inducing features (including multiple ORFs with internal termination codons that create a long 3\u2032 untranslated region) in CoV mRNAs led us to explore the interplay between the NMD pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in their degradation. Furthermore, CoV replication induced the inhibition of the NMD pathway, and N protein (a viral structural protein) had an NMD inhibitory function that protected viral mRNAs from rapid decay. Our data further suggest that the NMD pathway interferes with optimal viral replication by degrading viral mRNAs early in infection, before sufficient accumulation of N protein. Our study presents clear evidence for the biological importance of the NMD pathway in controlling the stability of mRNAs and the efficiency of replication of a cytoplasmic RNA virus.", "qid": 50, "docid": "o14tiixx", "rank": 47, "score": 9.701700210571289}, {"content": "Title: A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity Content: Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.", "qid": 50, "docid": "qq22z25y", "rank": 48, "score": 9.694000244140625}, {"content": "Title: Coordinate induction of IFN-\u03b1 and -\u03b3 by SARS-CoV also in the absence of virus replication Content: Abstract Background: Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV, characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication. This study is aimed at investigating the capability of SARS-CoV to activate IFN-\u03b1 and -\u03b3 expression in lymphomonocytes (PBMC) from healthy donors, evaluating whether viral replication is necessary for this activation. Results: SARS-CoV virus is able to induce both IFN-\u03b1 and -\u03b3 mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being the most effective. The time course curve indicated that IFN-\u03b1 mRNA induction peaked at 24 h.p.i,. whereas IFN-\u03b3 mRNA was still increasing at 48 h.p.i. Released IFN (both types) reached a plateau after 24\u201348 h.p.i. and remained rather stable over a 5-day period. A transient peak of negative strand viral RNA was detected after 1\u20132 days of infection, but neither infectious virus progeny yield nor newly produced viral genomic RNA could be evidenced in infected cultures, even after prolonged observation time (up to 13 days). Cocultivation of PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than exposure to live virus in eliciting IFN-\u03b1 and -\u03b3 induction. A combination of IFN-\u03b1 and -\u03b3 strongly inhibited SARS-CoV replication in Vero cells, while the single cytokines were much less effective. Conclusions: This study provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate induction of IFN-\u03b1 and -\u03b3 gene expression. Virus replication is not necessary for IFN induction since efficient IFN expression could be obtained also by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells. Concomitant activation of IFN-\u03b1 and -\u03b3 gene expression by SARS-CoV in vivo may be relevant for the pathogenesis of the disease, both for the possible involvement in immunomediated damage of the tissues and for the strong inhibition of SARS-CoV replication as a result of combined cytokine action.", "qid": 50, "docid": "zstmdt4n", "rank": 49, "score": 9.678500175476074}, {"content": "Title: SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in 'lasso' for the multi-faced virus Content: During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the least rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a 'cytokine storm' in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.", "qid": 50, "docid": "mxcfkyui", "rank": 50, "score": 9.672100067138672}, {"content": "Title: SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in \u2018lasso\u2019 for the multi-faced virus Content: During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the least rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a \u2018cytokine storm\u2019 in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.", "qid": 50, "docid": "xeq0dq6u", "rank": 51, "score": 9.672099113464355}, {"content": "Title: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019\u20132020 Content: Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019\u20132020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.", "qid": 50, "docid": "43gik8e3", "rank": 52, "score": 9.671299934387207}, {"content": "Title: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019-2020 Content: Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019-2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.", "qid": 50, "docid": "9yenf9w3", "rank": 53, "score": 9.67129898071289}, {"content": "Title: Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID\u201019 Pandemic: AASLD Expert Panel Consensus Statement Content: Coronavirus disease 2019 (COVID\u201019), the illness caused by the SARS\u2010CoV\u20102 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients but few are wholly equipped to manage this new disease. We all must do our part to prepare our patients, clinics, and hospitals for the drastic changes necessary to mitigate the spread of SARS\u2010CoV\u20102 or we risk overwhelming the capacity of our healthcare system. The goals of this document are to provide data on what is currently known about COVID\u201019, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID\u201019 pandemic on liver patients and healthcare providers.", "qid": 50, "docid": "8dsmw464", "rank": 54, "score": 9.63860034942627}, {"content": "Title: Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID-19 Pandemic: AASLD Expert Panel Consensus Statement Content: Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients but few are wholly equipped to manage this new disease. We all must do our part to prepare our patients, clinics, and hospitals for the drastic changes necessary to mitigate the spread of SARS-CoV-2 or we risk overwhelming the capacity of our healthcare system. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers.", "qid": 50, "docid": "im5lqh6d", "rank": 55, "score": 9.638599395751953}, {"content": "Title: [Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV)]. Content: The outbreak of 2019 novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same \u03b2-genus of coronavirus family. Base on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including the characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines cover all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many challenges with unknown knowledge, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.", "qid": 50, "docid": "4nrpcado", "rank": 56, "score": 9.635100364685059}, {"content": "Title: [Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV)] Content: The outbreak of 2019 novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same \u00df-genus of coronavirus family. Base on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including the characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines cover all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many challenges with unknown knowledge, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.", "qid": 50, "docid": "binxayw2", "rank": 57, "score": 9.635099411010742}, {"content": "Title: Optimizing the COVID-19 Intervention Policy in Scotland and the Case for Testing and Tracing Content: Unlike other European countries the UK has abandoned widespread testing and tracing of known SARS-CoV-2 carriers in mid-March. The reason given was that the pandemic was out of control and with wide community based spread it would not be possible to contain it by tracing any longer. Like other countries the UK has since relied on a lockdown as the main measure to contain the virus (or more precisely the reproduction number R at significant economic and social cost. It is clear that this level of lockdown cannot be sustained until a vaccine is available, yet it is not clear what an exit strategy would look like that avoids the danger of a second (or subsequent waves). In this paper we argue that, when used within a portfolio of intervention strategies, widespread testing and tracing leads to significant cost savings compared to using lockdown measures alone. While the effect is most pronounced if a large proportion of the infectious population can be identified and their contacts traced, under reasonable assumptions there are still significant savings even if the fraction of infectious people found by tracing is small. We also present a policy optimization model that finds, for given assumptions on the disease parameters, the best intervention strategy to contain the virus by varying the degree of tracing and lockdown measure (and vaccination once that option is available) over time. We run the model on data fitted to the published COVID-19 outbreak figures for Scotland. The model suggests an intervention strategy that keeps the number of COVID-19 deaths low using a combination of tracing and lockdown. This strategy would only require lockdown measures equivalent to a reduction of R to about 1.8--2.0 if lockdown was used alone, at acceptable economic cost, while the model finds no such strategy without tracing enabled.", "qid": 50, "docid": "73dwlakt", "rank": 58, "score": 9.629400253295898}, {"content": "Title: Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1\u20135). Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 50, "docid": "nhkd88yv", "rank": 59, "score": 9.624799728393555}, {"content": "Title: The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19 Content: The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.", "qid": 50, "docid": "9fnghyn4", "rank": 60, "score": 9.612000465393066}, {"content": "Title: Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells Content: Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.Communicated by Ramaswamy H. Sarma.", "qid": 50, "docid": "4nat5olo", "rank": 61, "score": 9.610600471496582}, {"content": "Title: Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells Content: Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use. Communicated by Ramaswamy H. Sarma", "qid": 50, "docid": "xoeokhrd", "rank": 62, "score": 9.610599517822266}, {"content": "Title: Podcast: Beating a killer coronavirus Content: As COVID-19 continues to spread, so does the effort to find treatment and vaccinations against SARS-CoV-2, the coronavirus that causes the disease Around the world, scientists are working nonstop on therapies they hope will stem the loss of life during this pandemic while trying to set us up to prevent future outbreaks What\u2019s not clear is which of these treatments will work Much about SARS-CoV-2 remains unknown In this episode of Stereo Chemistry, we dig into the efforts to beat the novel coronavirus and why in some cases it\u2019s like throwing spaghetti against the wall to see what sticks Learn more at http://cenm ag/coronapodcast", "qid": 50, "docid": "m5brxspf", "rank": 63, "score": 9.591300010681152}, {"content": "Title: Analysis of a SARS-CoV-2 infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation Content: Abstract Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject twenty-one days after the onset of clinical disease. Forty-five S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation, with limited clonal expansion and three bound the receptor binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine-design.", "qid": 50, "docid": "7ati571p", "rank": 64, "score": 9.577400207519531}, {"content": "Title: Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation Content: Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.", "qid": 50, "docid": "g4qak0bu", "rank": 65, "score": 9.577399253845215}, {"content": "Title: The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine Content: SARS-CoV-2 is a member of the coronaviridae family and is the etiological agent of the respiratory Coronavirus Disease 2019. The virus has spread rapidly around the world resulting in over two million cases and nearly 150,000 deaths as of April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 and SARS-CoV-2, respiratory complications derived from the infections have overwhelmed healthcare systems around the world. This virus is related to SARS-CoV-1, the virus that caused the 2002-2004 outbreak of Severe Acute Respiratory Syndrome. In January 2020, the Center for Structural Genomics of Infectious Diseases implemented a structural genomics pipeline to solve the structures of proteins essential for coronavirus replication-transcription. Here we show the first structure of the SARS-CoV-2 nsp10-nsp16 2\u2019-O-methyltransferase complex with S-adenosylmethionine at a resolution of 1.80 \u00c5. This heterodimer complex is essential for capping viral mRNA transcripts for efficient translation and to evade immune surveillance.", "qid": 50, "docid": "ywia2ok7", "rank": 66, "score": 9.554100036621094}, {"content": "Title: Convergent antibody responses to SARS-CoV-2 in convalescent individuals Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 50, "docid": "79891dfu", "rank": 67, "score": 9.55210018157959}, {"content": "Title: Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Content: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "qid": 50, "docid": "gof2of9o", "rank": 68, "score": 9.552099227905273}, {"content": "Title: The Importance Of Naturally Attenuated Sars\u2010Cov\u20102 In The Fight Against Covid\u201019 Content: The current SARS\u2010CoV\u20102 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID\u201019 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS\u2010CoV\u20102 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS\u2010CoV\u20102 would offer significant relief, although vaccine developers have warned that design, testing, and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (1), but the earliest vaccines were based on live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS\u2010CoV\u20102 will mutate and may naturally attenuate over time (2). What makes the current pandemic unique is that, thanks to state\u2010of\u2010the\u2010art nucleic acid sequencing technologies, we can follow in detail how SARS\u2010CoV\u20102 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS\u2010CoV\u20102 variants across the globe should be of key interest in our fight against the pandemic. This article is protected by copyright. All rights reserved.", "qid": 50, "docid": "kh54yctx", "rank": 69, "score": 9.550700187683105}, {"content": "Title: COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures. Content: A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a \"cordon sanitaire\" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.", "qid": 50, "docid": "qkl2yiqa", "rank": 70, "score": 9.545100212097168}, {"content": "Title: COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures Content: A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a \"cordon sanitaire\" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.", "qid": 50, "docid": "tswojeuv", "rank": 71, "score": 9.545099258422852}, {"content": "Title: High seroreactivity against SARS-CoV-2 Spike epitopes in a pre SARS-CoV-2 cohort: implications for antibody testing and vaccine design Content: Little is known about the quality of polyclonal antibody responses in COVID-19 patients, and how it correlates with disease severity or patients' prior exposure to other pathogens. The whole polyclonal antibody repertoire in a retrospective cohort of 538 individuals was mapped against SARS-CoV-2 spike (S) glycoprotein, the main target of antibody immune responses in SARS-CoV-2 infection. Bioinformatic predictions identified 15 major B cell epitopes for S of SARS-CoV-2. Several epitopes localised in RBD of S including those spanning the ACE2-binding site, the highly conserved cryptic epitope of the neutralizing antibody of SARS-CoV, and fusion/entry domains of HR1 and HR2 of S protein of SARS-CoV-2. Intriguingly, some of these epitopes have cross-reactivity to antigens of common pathogens, potentially affecting SARS-CoV-2 infection outcome. High level of anti-Spike SARS-CoV-2 seroreactivity in populations with no history of exposure to SARS-CoV-2 is of clinical relevance and could underpin better understanding of COVID-19 pathophysiology in different populations and provide a blueprint for design of effective vaccines and developing better strategies for antibody testing.", "qid": 50, "docid": "w98i9l5i", "rank": 72, "score": 9.541299819946289}, {"content": "Title: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review Content: BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "qid": 50, "docid": "998lscmk", "rank": 73, "score": 9.53219985961914}, {"content": "Title: The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines Content: The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern However, no specific antiviral treatments or vaccines are available yet This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2 An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020) The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China1 A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China2 COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3 0 days (range, 0 to 24 0), and the time from symptom onset to developing pneumonia is 4 0 days (range, 2 0 to 7 0)3 Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role3 Fever, dry cough, and fatigue are common symptoms at onset of COVID-194 Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans4,5 No specific antiviral treatments or vaccines are available because it is a new emerging viral disease Development of SARS-CoV-2-based vaccines is urgently required The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines6 The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no MN908947 3)7 Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and \u03b2-propiolactone8 The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus9 Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table 1) Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered", "qid": 50, "docid": "m88ha8ry", "rank": 74, "score": 9.527299880981445}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19. Content: INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss ten important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 50, "docid": "l7riy8ox", "rank": 75, "score": 9.508099555969238}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19 Content: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED: Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss 10 important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION: Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 50, "docid": "tst7ss76", "rank": 76, "score": 9.508098602294922}, {"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review Content: In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 50, "docid": "yyfuu197", "rank": 77, "score": 9.494099617004395}, {"content": "Title: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship Content: At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.", "qid": 50, "docid": "hechmemo", "rank": 78, "score": 9.42490005493164}, {"content": "Title: Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate Content: Coronaviruses (CoVs) are one of the largest groups of positive-sense RNA virus families within the Nidovirales order, which are further classified into four genera: alpha, beta, gamma, and delta. Coronaviruses have an extensive range of natural hosts and are known to be responsible for a broad spectrum of diseases in multiple species. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) that has unleashed a global threat to public health and the economy. Coronaviruses are extensively present in birds and mammals, with horseshoe bats (Rhinolophus affinis), being the reservoir for the ongoing SARS-CoV-2 that seems to have resulted from a zoonotic spillover to the human host, causing respiratory infections, lung injury and Acute Respiratory Distress Syndrome(ARDS). About six coronavirus serotypes are linked with the disease in humans, namely HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV. SARS-CoV-2 is the seventh CoV to infect humans. We analyzed the genome sequence of CoV-2 from isolates derived from China as well from India and encountered minute variations in their sequence. A cladogram analysis revealed the predominant strain circulating in India belongs to the A2a clad. We took one such strain (MT012098) and performed a rigorous in-silico genotypic and antigenic analysis to identify its relatedness to other strains. Further, we also performed a detailed prediction for B and T cell epitopes using BepiPred 2.0 server and NetCTL 1.2 server (DTU Bioinformatics), respectively. We hope this information may assist in an effective vaccine designing program against SARS-CoV-2.", "qid": 50, "docid": "12540n1s", "rank": 79, "score": 9.421699523925781}, {"content": "Title: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses. Content: OBJECTIVE SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "qid": 50, "docid": "deajwhx0", "rank": 80, "score": 9.418700218200684}, {"content": "Title: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses Content: OBJECTIVE: SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS: BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS: Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS: Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "qid": 50, "docid": "icwvm7jp", "rank": 81, "score": 9.418699264526367}, {"content": "Title: The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19? Content: The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.", "qid": 50, "docid": "1309xyi4", "rank": 82, "score": 9.416299819946289}, {"content": "Title: The innate immune system: fighting on the front lines or fanning the flames of COVID-19? Content: Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.", "qid": 50, "docid": "ebalebqq", "rank": 83, "score": 9.416298866271973}, {"content": "Title: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 Content: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung. IMPORTANCE Vaccines and new medicines are urgently needed to prevent spread of COVID-19 pandemic, reduce the symptoms, shorten the duration of disease, prevent virus spread in the body, and most importantly to save lives. One of the key drug targets could be angiotensin-converting enzyme 2 (ACE2), which is a crucial receptor for the corona virus (SARS-CoV-2). It is known that SARS coronavirus infections lead to worse outcome in the elderly and in males. Therefore, one aim of the present study was to investigate whether age or sex could contribute to the regulation of ACE2 expression. We also decided to explore the transcriptional regulation of ACE2 gene expression. Since data on ACE2 distribution is still conflicting, we aimed to get a more comprehensive view of the cell types expressing the receptor of SARS-CoV-2. Finally, we studied the coexpression of ACE2 with other genes and explored its putative functions using gene ontology enrichment analysis.", "qid": 50, "docid": "08vsaov7", "rank": 84, "score": 9.400799751281738}, {"content": "Title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target Content: A novel coronavirus recently identified in Wuhan, China (SARS-CoV-2) has expanded the number of highly pathogenic coronaviruses affecting humans. The SARS-CoV-2 represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging SARS-CoV-2 is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of SARS-CoV-2; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the SARS-CoV-2, and that domain 288-330 of S1 protein from the SARS-CoV-2 represents promising therapeutic and/or vaccine target.", "qid": 50, "docid": "3bc72zgr", "rank": 85, "score": 9.375800132751465}, {"content": "Title: Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report Content: Abstract In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 g, 30 g, or 100 g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.", "qid": 50, "docid": "akbq0ogs", "rank": 86, "score": 9.373600006103516}, {"content": "Title: Management of non traumatic surgical emergencies during the COVID-19 pandemia Content: In December 2019, in Wuhan, China, the first cases of what would be known as COVID-19, a disease caused by an RNA virus called SARS-CoV-2, were described Its spread was rapid and wide, leading the World Health Organization to declare a pandemic in March 2020 The disease has distinct clinical presentations, from asymptomatic to critical cases, with high lethality Parallel to this, patients with non-traumatic surgical emergencies, such as acute appendicitis and cholecystitis, continue to be treated at the emergency services In this regard, there were several doubts on how to approach these cases, among them: how to quickly identify the patient with COVID-19, what is the impact of the abdominal surgical disease and its treatment on the evolution of patients with COVID-19, in addition to the discussion about the role of the non-operative treatment for abdominal disease under these circumstances In this review, we discuss these problems based on the available evidence", "qid": 50, "docid": "vnq1fjwy", "rank": 87, "score": 9.35319995880127}, {"content": "Title: Type I and Type III IFN Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures Content: The newly emerged human coronavirus, SARS-CoV-2, has caused a pandemic of respiratory illness. The innate immune response is critical for protection against Coronaviruses. However, little is known about the interplay between the innate immune system and SARS-CoV-2. Here, we modeled SARS-CoV-2 infection using primary human airway epithelial (pHAE) cultures, which are maintained in an air-liquid interface. We found that SARS-CoV-2 infects and replicates in pHAE cultures and is directionally released on the apical, but not basolateral surface. Transcriptional profiling studies found that infected pHAE cultures had a molecular signature dominated by pro-inflammatory cytokines and chemokine induction, including IL-6, TNF\u03b1, CXCL8. We also identified NF-\u03baB and ATF4 transcription factors as key drivers of this pro-inflammatory cytokine response. Surprisingly, we observed a complete lack of a type I or III IFN induction during SARS-CoV-2 infection. Pre-treatment or post-treatment with type I and III IFNs dramatically reduced virus replication in pHAE cultures and this corresponded with an upregulation of antiviral effector genes. Our findings demonstrate that SARS-CoV-2 induces a strong pro-inflammatory cytokine response yet blocks the production of type I and III IFNs. Further, SARS-CoV-2 is sensitive to the effects of type I and III IFNs, demonstrating their potential utility as therapeutic options to treat COVID-19 patients. IMPORTANCE The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines or antivirals approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. SARS-CoV-2 infection of primary human airway epithelial cultures induces a strong pro-inflammatory cytokine response yet blocks the production of type I and III IFNs. Further, SARS-CoV-2 is sensitive to the effects of type I and III IFNs, demonstrating their potential utility as therapeutic options to treat COVID-19 patients.", "qid": 50, "docid": "2s1io2fg", "rank": 88, "score": 9.312999725341797}, {"content": "Title: Severe acute respiratory syndrome coronavirus triggers apoptosis via protein kinase R but is resistant to its antiviral activity. Content: In this study, infection of 293/ACE2 cells with severe acute respiratory syndrome coronavirus (SARS-CoV) activated several apoptosis-associated events, namely, cleavage of caspase-3, caspase-8, and poly(ADP-ribose) polymerase 1 (PARP), and chromatin condensation and the phosphorylation and hence inactivation of the eukaryotic translation initiation factor 2alpha (eIF2alpha). In addition, two of the three cellular eIF2alpha kinases known to be virus induced, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), were activated by SARS-CoV. The third kinase, general control nonderepressible-2 kinase (GCN2), was not activated, but late in infection the level of GCN2 protein was significantly reduced. Reverse transcription-PCR analyses revealed that the reduction of GCN2 protein was not due to decreased transcription or stability of GCN2 mRNA. The specific reduction of PKR protein expression by antisense peptide-conjugated phosphorodiamidate morpholino oligomers strongly reduced cleavage of PARP in infected cells. Surprisingly, the knockdown of PKR neither enhanced SARS-CoV replication nor abrogated SARS-CoV-induced eIF2alpha phosphorylation. Pretreatment of cells with beta interferon prior to SARS-CoV infection led to a significant decrease in PERK activation, eIF2alpha phosphorylation, and SARS-CoV replication. The various effects of beta interferon treatment were found to function independently on the expression of PKR. Our results show that SARS-CoV infection activates PKR and PERK, leading to sustained eIF2alpha phosphorylation. However, virus replication was not impaired by these events, suggesting that SARS-CoV possesses a mechanism to overcome the inhibitory effects of phosphorylated eIF2alpha on viral mRNA translation. Furthermore, our data suggest that viral activation of PKR can lead to apoptosis via a pathway that is independent of eIF2alpha phosphorylation.", "qid": 50, "docid": "rg1z4dul", "rank": 89, "score": 9.310400009155273}, {"content": "Title: Covid-19 in pregnant women and babies: What pediatricians need to know Content: Beginning in late 2019, a novel coronavirus labeled SARS-CoV-2 spread around the world, affecting millions. The impact of the disease on patients and on health care delivery has been unprecedented. Here, we review what is currently known about the effects of the virus and its clinical condition, Covid-19 in areas of relevance to those providing care to neonates. While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this. Viral carriage prevalence based on universal screening show that rates vary from 13% in \u201chot spots\u201d such as New York City, to 3% in areas with lower cases. Vertical transmission risks are unknown but 3.1% of 311 babies born to mothers with Covid-19 were positive within a week of birth. The clinical description of 26 neonates < 30 days of age showed no deaths and only one requiring intensive care. Risks for breast-feeding and for milk banks are discussed.", "qid": 50, "docid": "fllqdn4s", "rank": 90, "score": 9.302599906921387}, {"content": "Title: A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal Content: A wide range of RNA viruses use programmed \u22121 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed \u22121 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics.", "qid": 50, "docid": "a22s8xyz", "rank": 91, "score": 9.293299674987793}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2 Content: Severe Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 \u2013 a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.", "qid": 50, "docid": "xq1cxrvf", "rank": 92, "score": 9.28499984741211}, {"content": "Title: Pixatimod (PG545), a clinical-stage heparan sulfate mimetic, is a potent inhibitor of the SARS-CoV-2 virus Content: A major global effort is currently ongoing to search for therapeutics and vaccines to treat or prevent infection by the SARS-CoV-2 virus. Repurposing existing entities is one attractive approach. The heparan sulfate mimetic pixatimod is a clinical-stage synthetic sulfated compound that is a potent inhibitor of the glycosidase heparanase, and has known anti-cancer, anti-inflammatory and also antiviral properties. Here we show that pixatimod binds directly to the SARS-CoV-2 spike protein S1 receptor binding domain (RBD) and alters its conformation. Notably, this site overlaps with the known ACE2 binding site in the S1 RBD. We find that pixatimod inhibits binding of recombinant S1 RBD to Vero cells which express the ACE2 receptor. Moreover, in assays with three different isolates of live SARS-CoV-2 virus we show that pixatimod effectively inhibits viral infection of Vero cells. Importantly, its potency is well within its safe therapeutic dose range. These data provide evidence that pixatimod is a potent antiviral agent against SARS-CoV-2. Together with its other known activities this provides a strong rationale for its clinical investigation as a new multimodal therapeutic for the current COVID-19 pandemic.", "qid": 50, "docid": "rirbg1he", "rank": 93, "score": 9.274800300598145}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS\u2010CoV\u20102 Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS\u2010CoV\u20102) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS\u2010CoVs and Middle East Respiratory Syndrome coronavirus (MERS\u2010CoVs), the detailed information about SARS\u2010CoV\u20102 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high\u2010throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS\u2010CoV\u20102 proteins and structures. Here we report two high\u2010resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.", "qid": 50, "docid": "o0x269k5", "rank": 94, "score": 9.265600204467773}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2 Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS-CoVs and Middle East Respiratory Syndrome coronavirus (MERS-CoVs), the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.", "qid": 50, "docid": "vosgahs3", "rank": 95, "score": 9.265599250793457}, {"content": "Title: New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Content: ABSTRACT Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.", "qid": 50, "docid": "da61tfr9", "rank": 96, "score": 9.265299797058105}, {"content": "Title: New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Content: Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.", "qid": 50, "docid": "ye7l5p8k", "rank": 97, "score": 9.265298843383789}, {"content": "Title: Putative Roles for Peptidylarginine Deiminases in COVID-19. Content: Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients' tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1-6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.", "qid": 50, "docid": "63umnf0b", "rank": 98, "score": 9.25629997253418}, {"content": "Title: Putative Roles for Peptidylarginine Deiminases in COVID-19 Content: Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients' tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1-6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.", "qid": 50, "docid": "6khytngb", "rank": 99, "score": 9.256299018859863}, {"content": "Title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization Content: STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? SUMMARY ANSWER ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization. WHAT IS KNOWN ALREADY ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. STUDY DESIGN, SIZE, DURATION Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression. MAIN RESULTS AND THE ROLE OF CHANCE In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss. STUDY FUNDINGS/COMPETING INTEREST(S) This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.", "qid": 50, "docid": "0xyrmk5a", "rank": 100, "score": 9.209500312805176}]}
{"query": "has social distancing had an impact on slowing the spread of COVID-19?", "hits": [{"content": "Title: U.S. county level analysis to determine If social distancing slowed the spread of COVID-19 Content: OBJECTIVE. To analyze the effectiveness of social distancing in the United States (U.S.). METHODS. A novel cell-phone ping data was used to quantify the measures of social distancing by all U.S. counties. RESULTS. Using a difference-in-difference approach results show that social distancing has been effective in slowing the spread of COVID-19. CONCLUSIONS. As policymakers face the very difficult question of the necessity and effectiveness of social distancing across the U.S., counties where the policies have been imposed have effectively increased social distancing and have seen slowing the spread of COVID-19. These results might help policymakers to make the public understand the risks and benefits of the lockdown.", "qid": 10, "docid": "pn02p843", "rank": 1, "score": 14.22659969329834}, {"content": "Title: The Changing Face of Orthopedic Education: Searching for the New Reality After COVID-19 Content: Abstract The COVID-19 pandemic has had immediate impact on the practice of medicine and orthopaedic education. As the practice of social distancing has been put into place to help slow the spread of disease as well as to conserve medical supplies and equipment, elective surgery has come to a grinding halt. This dramatic change has forced our leaders to critically evaluate the delivery of education and skills training for our residents, fellows as well as all orthopaedic surgeons. We must continue to develop technologies such as virtual meeting platforms, distance learning, simulation-based training, virtual reality andaugmented reality to augment the new world of orthopaedic education.", "qid": 10, "docid": "sb45v082", "rank": 2, "score": 13.715900421142578}, {"content": "Title: Fever and mobility data indicate social distancing has reduced incidence of communicable disease in the United States Content: In March of 2020, many U.S. state governments encouraged or mandated restrictions on social interactions to slow the spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2 that has spread to nearly 180 countries. Estimating the effectiveness of these social-distancing strategies is challenging because surveillance of COVID-19 has been limited, with tests generally being prioritized for high-risk or hospitalized cases according to temporally and regionally varying criteria. Here we show that reductions in mobility across U.S. counties with at least 100 confirmed cases of COVID-19 led to reductions in fever incidences, as captured by smart thermometers, after a mean lag of 6.5 days ($90\\%$ within 3--10 days) that is consistent with the incubation period of COVID-19. Furthermore, counties with larger decreases in mobility subsequently achieved greater reductions in fevers ($p<0.01$), with the notable exception of New York City and its immediate vicinity. These results indicate that social distancing has reduced the transmission of influenza like illnesses, including COVID 19, and support social distancing as an effective strategy for slowing the spread of COVID-19.", "qid": 10, "docid": "cb5ebiiv", "rank": 3, "score": 13.668600082397461}, {"content": "Title: Early transmission dynamics of COVID-19 in a southern hemisphere setting: Lima-Peru: February 29(th)\u2013March 30(th), 2020. Content: The COVID-19 pandemic that emerged in Wuhan China has generated substantial morbidity and mortality impact around the world during the last four months. The daily trend in reported cases has been rapidly rising in Latin America since March 2020 with the great majority of the cases reported in Brazil followed by Peru as of April 15(th), 2020. Although Peru implemented a range of social distancing measures soon after the confirmation of its first case on March 6(th), 2020, the daily number of new COVID-19 cases continues to accumulate in this country. We assessed the early COVID-19 transmission dynamics and the effect of social distancing interventions in Lima, Peru. We estimated the reproduction number, R, during the early transmission phase in Lima from the daily series of imported and autochthonous cases by the date of symptoms onset as of March 30(th), 2020. We also assessed the effect of social distancing interventions in Lima by generating short-term forecasts grounded on the early transmission dynamics before interventions were put in place. Prior to the implementation of the social distancing measures in Lima, the local incidence curve by the date of symptoms onset displays near exponential growth dynamics with the mean scaling of growth parameter, p, estimated at 0.9 (95%CI: 0.9,1.0) and the reproduction number at 2.3 (95% CI: 2.0, 2.5). Our analysis indicates that school closures and other social distancing interventions have helped slow down the spread of the novel coronavirus, with the nearly exponential growth trend shifting to an approximately linear growth trend soon after the broad scale social distancing interventions were put in place by the government. While the interventions appear to have slowed the transmission rate in Lima, the number of new COVID-19 cases continue to accumulate, highlighting the need to strengthen social distancing and active case finding efforts to mitigate disease transmission in the region.", "qid": 10, "docid": "17wpnfao", "rank": 4, "score": 13.56190013885498}, {"content": "Title: Early transmission dynamics of COVID-19 in a southern hemisphere setting: Lima-Peru: February 29th\u2013March 30th, 2020. Content: The COVID-19 pandemic that emerged in Wuhan China has generated substantial morbidity and mortality impact around the world during the last four months. The daily trend in reported cases has been rapidly rising in Latin America since March 2020 with the great majority of the cases reported in Brazil followed by Peru as of April 15th, 2020. Although Peru implemented a range of social distancing measures soon after the confirmation of its first case on March 6th, 2020, the daily number of new COVID-19 cases continues to accumulate in this country. We assessed the early COVID-19 transmission dynamics and the effect of social distancing interventions in Lima, Peru. We estimated the reproduction number, R, during the early transmission phase in Lima from the daily series of imported and autochthonous cases by the date of symptoms onset as of March 30th, 2020. We also assessed the effect of social distancing interventions in Lima by generating short-term forecasts grounded on the early transmission dynamics before interventions were put in place. Prior to the implementation of the social distancing measures in Lima, the local incidence curve by the date of symptoms onset displays near exponential growth dynamics with the mean scaling of growth parameter, p, estimated at 0.9 (95%CI: 0.9,1.0) and the reproduction number at 2.3 (95% CI: 2.0, 2.5). Our analysis indicates that school closures and other social distancing interventions have helped slow down the spread of the novel coronavirus, with the nearly exponential growth trend shifting to an approximately linear growth trend soon after the broad scale social distancing interventions were put in place by the government. While the interventions appear to have slowed the transmission rate in Lima, the number of new COVID-19 cases continue to accumulate, highlighting the need to strengthen social distancing and active case finding efforts to mitigate disease transmission in the region.", "qid": 10, "docid": "5296m6d8", "rank": 5, "score": 13.561899185180664}, {"content": "Title: Early transmission dynamics of COVID-19 in a southern hemisphere setting: Lima-Peru: February 29th-March 30th, 2020 Content: The COVID-19 pandemic that emerged in Wuhan China has generated substantial morbidity and mortality impact around the world during the last four months. The daily trend in reported cases has been rapidly rising in Latin America since March 2020 with the great majority of the cases reported in Brazil followed by Peru as of April 15th, 2020. Although Peru implemented a range of social distancing measures soon after the confirmation of its first case on March 6th, 2020, the daily number of new COVID-19 cases continues to accumulate in this country. We assessed the early COVID-19 transmission dynamics and the effect of social distancing interventions in Lima, Peru. We estimated the reproduction number, R, during the early transmission phase in Lima from the daily series of imported and autochthonous cases by the date of symptoms onset as of March 30th, 2020. We also assessed the effect of social distancing interventions in Lima by generating short-term forecasts grounded on the early transmission dynamics before interventions were put in place. Prior to the implementation of the social distancing measures in Lima, the local incidence curve by the date of symptoms onset displays near exponential growth dynamics with the mean scaling of growth parameter, p, estimated at 0.9 (95%CI: 0.9,1.0) and the reproduction number at 2.3 (95% CI: 2.0, 2.5). Our analysis indicates that school closures and other social distancing interventions have helped slow down the spread of the novel coronavirus, with the nearly exponential growth trend shifting to an approximately linear growth trend soon after the broad scale social distancing interventions were put in place by the government. While the interventions appear to have slowed the transmission rate in Lima, the number of new COVID-19 cases continue to accumulate, highlighting the need to strengthen social distancing and active case finding efforts to mitigate disease transmission in the region.", "qid": 10, "docid": "5a7ma7nf", "rank": 6, "score": 13.561898231506348}, {"content": "Title: Isolation and contact tracing can tip the scale to containment of COVID-19 in populations with social distancing Content: Background: Novel coronavirus (SARS-CoV-2) has extended its range of transmission in all parts of the world, with substantial variation in rates of transmission and severity of associated disease. Many countries have implemented social distancing as a measure to control further spread. Methods: We evaluate whether and under which conditions containment or slowing down COVID-19 epidemics are possible by isolation and contact tracing in settings with various levels of social distancing. We use a stochastic transmission model in which every person generates novel infections according to a probability distribution that is affected by the incubation period distribution (time from infection to symptoms), distribution of the latent period (time from infection to onset of infectiousness), and overall transmissibility. The model distinguishes between close contacts (e.g., within a household) and other contacts in the population. Social distancing affects the number of contacts outside but not within the household. Findings: The proportion of asymptomatic or unascertained cases has a strong impact on the controllability of the disease. If the proportion of asymptomatic infections is larger than 30%, contact tracing and isolation cannot achieve containment for an R0 of 2.5. Achieving containment by social distancing requires a reduction of numbers of non-household contacts by around 90%. Depending on the realized level of contact reduction, tracing and isolation of only household contacts, or of household and non-household contacts are necessary to reduce the effective reproduction number to below 1. A combination of social distancing with isolation and contact tracing leads to synergistic effects that increase the prospect of containment. Interpretation: Isolation and contact tracing can be an effective means to slow down epidemics, but only if the majority of cases are ascertained. In a situation with social distancing, contact tracing can act synergistically and tip the scale towards containment, and can therefore be a tool for controlling COVID-19 epidemics as part of an exit strategy from current lockdown measures.", "qid": 10, "docid": "6a6njt3u", "rank": 7, "score": 13.5201997756958}, {"content": "Title: Impact of self-imposed prevention measures and short-term government intervention on mitigating and delaying a COVID-19 epidemic Content: Background: With new cases of COVID-19 surging around the world, many countries have to prepare for moving beyond the containment phase. Prediction of the effectiveness of non-case-based interventions for mitigating, delaying or preventing the epidemic is urgent, especially for countries affected by the ongoing seasonal influenza activity. Methods: We developed a transmission model to evaluate the impact of self-imposed prevention measures (handwashing, mask-wearing, and social distancing) due to the spread of COVID-19 awareness and of short-term government-imposed social distancing on the peak number of diagnoses, attack rate and time until the peak number of diagnoses. Findings: For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate, diminish and postpone the peak number of diagnoses. A large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government interventions can only delay the peak (by at most 7 months for a 3-month intervention). Interpretation: Handwashing, mask-wearing and social distancing as a reaction to information dissemination about COVID-19 can be effective strategies to mitigate and delay the epidemic. We stress the importance of rapidly spreading awareness on the use of these self-imposed prevention measures in the population. Early-initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. Keywords: SARS-CoV-2, COVID-19, mathematical model, prevention measures, mitigation, epidemic control, disease awareness, social distancing, handwashing, mask-wearing", "qid": 10, "docid": "xfjexm5b", "rank": 8, "score": 13.124300003051758}, {"content": "Title: Psychological Outcomes Associated with Stay-at-Home Orders and the Perceived Impact of COVID-19 on Daily Life Content: The COVID-19 pandemic has resulted in the widespread implementation of extraordinary physical distancing interventions (e.g., stay-at-home orders) to slow the spread of the virus. Although vital, these interventions may be socially and economically disruptive, contributing to adverse psychological outcomes. This study examined relations of both stay-at-home orders and the perceived impact of COVID-19 on daily life to psychological outcomes (depression, health anxiety, financial worry, social support, and loneliness) in a nationwide U.S. community adult sample (N = 500; 47% women, mean age = 40). Participants completed questionnaires assessing psychological outcomes, stay-at-home order status, and COVID-19\u2019s impact on their daily life. Being under a stay-at-home order was associated with greater health anxiety, financial worry, and loneliness. Moreover, the perceived impact of COVID-19 on daily life was positively associated with health anxiety, financial worry, and social support, but negatively associated with loneliness. Findings highlight the importance of social connection to mitigate negative psychological consequences of the COVID-19 pandemic.", "qid": 10, "docid": "c7l88gjn", "rank": 9, "score": 12.841899871826172}, {"content": "Title: Psychological Outcomes Associated with Stay-at-Home Orders and the Perceived Impact of COVID-19 on Daily Life Content: The COVID-19 pandemic has resulted in the widespread implementation of extraordinary physical distancing interventions (e.g., stay-at-home orders) to slow the spread of the virus. Although vital, these interventions may be socially and economically disruptive, contributing to adverse psychological outcomes. This study examined relations of both stay-at-home orders and the perceived impact of COVID-19 on daily life to psychological outcomes (depression, health anxiety, financial worry, social support, and loneliness) in a nationwide U.S. community adult sample (N = 500; 47% women, mean age = 40). Participants completed questionnaires assessing psychological outcomes, stay-at-home order status, and COVID-19's impact on their daily life. Being under a stay-at-home order was associated with greater health anxiety, financial worry, and loneliness. Moreover, the perceived impact of COVID-19 on daily life was positively associated with health anxiety, financial worry, and social support, but negatively associated with loneliness. Findings highlight the importance of social connection to mitigate negative psychological consequences of the COVID-19 pandemic.", "qid": 10, "docid": "rmv5kg3w", "rank": 10, "score": 12.841898918151855}, {"content": "Title: Insights into the impact of COVID-19 on household travel and activities in Australia \u2013 The early days under restrictions Content: When 2020 began, we had no idea what was to unfold globally as we learnt about the Novel-Coronavirus in Wuhan, in the Hubei province of China. As this virus spread rapidly, it became a matter of time before many countries began to implement measures to try and contain the spread of the disease. COVID-19 as it is referred to, resulted in two main approaches to fighting the viral pandemic, either through a progressive set of measures to slow down the number of identified cases designed to \u2018flatten the curve\u2019 over time (anticipated to be at least six months), or to attack it by the severest of measures including a total lock-down and/or herding exposure to fast track \u2018immunisation\u2019 while we await a vaccine. The paper reports the findings from the first phase of an ongoing survey designed to identify the changing patterns in travel activity of Australian residents as a result of the stage 2 restrictions imposed by the Australian government. The main restrictions, in addition to social distancing of at least 1.5 m, are closure of entry to Australia (except residents returning), and closure of non-essential venues such as night clubs, restaurants, mass attendee sporting events, churches, weddings, and all social gatherings in any circumstance. With some employers encouraging working from home and others requiring it, in addition to job losses, and many children attending school online from home, the implications on travel activity is extreme. We identify the initial impacts associated with the first month of stricter social distancing measures introduced in Australia.", "qid": 10, "docid": "shw3xnu3", "rank": 11, "score": 12.810999870300293}, {"content": "Title: Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France Content: Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.", "qid": 10, "docid": "smndijko", "rank": 12, "score": 12.75220012664795}, {"content": "Title: The projected impact of mitigation and suppression strategies on the COVID-19 epidemic in Senegal: A modelling study Content: Background: Physical distancing measures that reduce social contacts have formed a key part of national COVID-19 containment and mitigation strategies. Many Sub-Saharan African nations are now facing increasing numbers of cases of COVID-19 and there is a need to understand what levels of measures may be required to successfully reduce transmission. Methods: We collated epidemiological data along with information on key COVID-19 specific response policies and health system capacity estimates for services needed to treat COVID-19 patients in Senegal. We calibrated an age-structured SEIR model to these data to capture transmission dynamics accounting for demography, contact patterns, hospital capacity and disease severity. We simulated the impact of mitigation and suppression strategies focussed on reducing social contact rates. Results: Senegal acted promptly to contain the spread of SARS-CoV-2 and as a result has reduced the reproduction number from 1.9 (95% CI 1.7-2.2) to 1.3 (95% CI 1.2-1.5), which has slowed but not fully interrupted transmission. We estimate that continued spread is likely to peak in October, and to overwhelm the healthcare system with an estimated 77,400 deaths(95% CI 55,270-100,700). Further reductions in contact rates to suppress transmission (Rt<1) could significantly reduce this burden on healthcare services and improve overall health outcomes. Conclusions: Our results demonstrate that Senegal has already significantly reduced transmission. Enhanced physical distancing measures and rapid scale up of hospital capacity is likely to be needed to reduce mortality and protect healthcare infrastructure from high levels of demand.", "qid": 10, "docid": "x40l8ljx", "rank": 13, "score": 12.714300155639648}, {"content": "Title: Releasing the lockdown in the UK Covid-19 epidemic: a stochastic model Content: Abstract Background In a classic epidemic, the infected population has an early exponential phase, before slowing and fading to its peak. Mitigating interventions may change the exponent during the rising phase and a plateau can replace a peak. With interventions comes the risk that relaxation causes a second-wave. In the UK Covid-19 epidemic, infections cannot be counted, but their influence is seen in the curve of the mortality data. This work simulated social distancing and the lockdown in the UK Covid-19 epidemic to explore strategies for relaxation. Methods Cumulative mortality data was transposed 20 days earlier to identify three doubling periods separated by the 17th March - social distancing, and 23rd March - lockdown. A set of stochastic processes simulated viral transmission between interacting individuals using Covid-19 incubation and illness durations. Social distancing and restrictions on interactions were imposed and later relaxed. Principal Findings Daily mortality data, consistent with that seen in the UK Covid-19 epidemic to 24th April 2020 was simulated. This output predicts that under a lockdown maintained till early July 2020, UK deaths will exceed 31,000, but leave a large susceptible population and a requirement for vaccination or quarantine. An earlier staged relaxation carries a risk of a second-wave. The model allows exploration of strategies for lifting the lockdown. Interpretation Social distancing and the lockdown have had an impressive impact on the UK Covid-19 epidemic and saved lives, caution is now needed in planning its relaxation.", "qid": 10, "docid": "ru0av4io", "rank": 14, "score": 12.475299835205078}, {"content": "Title: Optimal control of the COVID-19 pandemic with non-pharmaceutical interventions Content: The COVID-19 pandemic has forced societies across the world to resort to social distancing to slow the spread of the SARS-CoV-2 virus. Due to the economic impacts of social distancing, there is growing desire to relax these measures. To characterize a range of possible strategies for control and to understand their consequences, we performed an optimal control analysis of a mathematical model of SARS-CoV-2 transmission. Given that the pandemic is already underway and controls have already been initiated, we calibrated our model to data from the US and focused our analysis on optimal controls from May 2020 through December 2021. We found that a major factor that differentiates strategies that prioritize lives saved versus reduced time under control is how quickly control is relaxed once social distancing restrictions expire in May 2020. Strategies that maintain control at a high level until summer 2020 allow for tapering of control thereafter and minimal deaths, whereas strategies that relax control in the short term lead to fewer options for control later and a higher likelihood of exceeding hospital capacity. Our results also highlight that the potential scope for controlling COVID-19 until a vaccine is available depends on epidemiological parameters about which there is still considerable uncertainty, including the basic reproduction number and the effectiveness of social distancing. In light of those uncertainties, our results do not constitute a quantitative forecast and instead provide a qualitative portrayal of possible outcomes from alternative approaches to control.", "qid": 10, "docid": "lnv8yi9l", "rank": 15, "score": 12.458999633789062}, {"content": "Title: No Place Like Home: Cross-National Data Analysis of the Efficacy of Social Distancing During the COVID-19 Pandemic Content: BACKGROUND: In the absence of a cure in the time of a pandemic, social distancing measures seem to be the most effective intervention to slow the spread of disease. Various simulation-based studies have been conducted to investigate the effectiveness of these measures. While those studies unanimously confirm the mitigating effect of social distancing on disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. However, real transactional data can reduce uncertainty and provide a less noisy picture of the effectiveness of social distancing. OBJECTIVE: The aim of this paper was to integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics from the European Centre for Disease Prevention and Control) to study the role of social distancing policies in 26 countries and analyze the transmission rate of the coronavirus disease (COVID-19) pandemic over the course of 5 weeks. METHODS: Relying on the susceptible-infected-recovered (SIR) model and official COVID-19 reports, we first calculated the weekly transmission rate (\u00df) of COVID-19 in 26 countries for 5 consecutive weeks. Then, we integrated these data with the Google and Apple mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between the mobility factors and \u00df values. RESULTS: Gradient boosted trees regression analysis showed that changes in mobility patterns resulting from social distancing policies explain approximately 47% of the variation in the disease transmission rates. CONCLUSIONS: Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing the spread of COVID-19. In addition to providing less noisy and more generalizable support for the idea of social distancing, we provide specific insights for public health policy makers regarding locations that should be given higher priority for enforcing social distancing measures.", "qid": 10, "docid": "qekxxsfy", "rank": 16, "score": 12.450400352478027}, {"content": "Title: Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave Content: Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.", "qid": 10, "docid": "4sxsyr6k", "rank": 17, "score": 12.437899589538574}, {"content": "Title: The trajectory of loneliness in response to COVID-19 Content: Social distancing and \"stay-at-home\" orders are essential to contain the coronavirus outbreak (COVID-19), but there is concern that these measures will increase feelings of loneliness, particularly in vulnerable groups. The present study examined change in loneliness in response to the social restriction measures taken to control the coronavirus spread. A nationwide sample of American adults (N = 1,545; 45% women; ages 18 to 98, M = 53.68, SD = 15.63) was assessed on three occasions: in late January/early February 2020 (before the outbreak), in late March (during the President's initial \"15 Days to Slow the Spread\" campaign), and in late April (during the \"stay-at-home\" policies of most states). Contrary to expectations, there were no significant mean-level changes in loneliness across the three assessments (d = .04, p > .05). In fact, respondents perceived increased support from others over the follow-up period (d = .19, p < .01). Older adults reported less loneliness overall compared to younger age groups but had an increase in loneliness during the acute phase of the outbreak (d = .14, p < .05). Their loneliness, however, leveled off after the issuance of stay-at-home orders. Individuals living alone and those with at least one chronic condition reported feeling lonelier at baseline but did not increase in loneliness during the implementation of social distancing measures. Despite some detrimental impact on vulnerable individuals, in the present sample, there was no large increase in loneliness but remarkable resilience in response to COVID-19. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 10, "docid": "nbv7zc4v", "rank": 18, "score": 12.418399810791016}, {"content": "Title: The trajectory of loneliness in response to COVID-19. Content: Social distancing and \"stay-at-home\" orders are essential to contain the coronavirus outbreak (COVID-19), but there is concern that these measures will increase feelings of loneliness, particularly in vulnerable groups. The present study examined change in loneliness in response to the social restriction measures taken to control the coronavirus spread. A nationwide sample of American adults (N = 1,545; 45% women; ages 18 to 98, M = 53.68, SD = 15.63) was assessed on three occasions: in late January/early February 2020 (before the outbreak), in late March (during the President's initial \"15 Days to Slow the Spread\" campaign), and in late April (during the \"stay-at-home\" policies of most states). Contrary to expectations, there were no significant mean-level changes in loneliness across the three assessments (d = .04, p > .05). In fact, respondents perceived increased support from others over the follow-up period (d = .19, p < .01). Older adults reported less loneliness overall compared to younger age groups but had an increase in loneliness during the acute phase of the outbreak (d = .14, p < .05). Their loneliness, however, leveled off after the issuance of stay-at-home orders. Individuals living alone and those with at least one chronic condition reported feeling lonelier at baseline but did not increase in loneliness during the implementation of social distancing measures. Despite some detrimental impact on vulnerable individuals, in the present sample, there was no large increase in loneliness but remarkable resilience in response to COVID-19. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 10, "docid": "zzgiluha", "rank": 19, "score": 12.4183988571167}, {"content": "Title: The effect of COVID-19 and subsequent social distancing on travel behavior Content: Abstract The spread of the COVID-19 virus has resulted in unprecedented measures restricting travel and activity participation in many countries. Social distancing, i.e., reducing interactions between individuals in order to slow down the spread of the virus, has become the new norm. In this viewpoint I will discuss the potential implications of social distancing on daily travel patterns. Avoiding social contact might completely change the number and types of out-of-home activities people perform, and how people reach these activities. It can be expected that the demand for travel will reduce and that people will travel less by public transport. Social distancing might negatively affect subjective well-being and health status, as it might result in social isolation and limited physical activity. As a result, walking and cycling, recreationally or utilitarian, can be important ways to maintain satisfactory levels of health and well-being. Policymakers and planners should consequently try to encourage active travel, while public transport operators should focus on creating ways to safely use public transport.", "qid": 10, "docid": "ocwetgv6", "rank": 20, "score": 12.415900230407715}, {"content": "Title: Evaluation of Turkish social distancing measures on the spread of COVID-19 Content: The coronavirus disease (COVID-19) affecting across the globe. The government of different countries has adopted various policies to contain this epidemic and the most common were social distancing and lockdown. We use a simple log-linear model with intercept and trend break to evaluate whether the measures are effective preventing/slowing down the spread of the disease in Turkey. We estimate the model parameters from the Johns Hopkins University (2020) epidemic data between 15th March and 16th April 2020. Our analysis revealed that the measures can slow down the outbreak. We can reduce the epidemic size and prolong the time to arrive at the epidemic peak by seriously following the measures suggested by the authorities.", "qid": 10, "docid": "uwix8ftr", "rank": 21, "score": 12.375499725341797}, {"content": "Title: No Place Like Home: A Cross-National Assessment of the Efficacy of Social Distancing during the COVID-19 Pandemic. Content: BACKGROUND In the absence of a cure in the time of pandemics, social distancing measures seem to be the most effective intervention to slow down the spread of disease. Various simulation-based studies have been conducted in the past to investigate the effectiveness of such measures. While those studies unanimously confirm the mitigating effect of social distancing on the disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. A real transactional data, however, can reduce the uncertainty and provide a less noisy picture of social distancing effectiveness. OBJECTIVE In this paper, we integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics data from ECDC) to study the role of social distancing policies in 26 countries wherein the transmission rate of the COVID-19 pandemic is analyzed over the course of five weeks. METHODS Relying on the SIR model and official COVID-19 reports, we first calculated the weekly transmission rate (\u03b2) of the coronavirus disease in 26 countries for five consecutive weeks. Then we integrated that with the Google's and Apple's mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between mobility factors and \u03b2 values. RESULTS Gradient Boosted Trees (GBT) regression analysis showed that changes in mobility patterns, resulted from social distancing policies, explain around 47% of the variation in the disease transmission rate. CONCLUSIONS Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing down the spread of the disease. Apart from providing less noisy and more generalizable support for the whole social distancing idea, we provide specific insights for public health policy-makers as to what locations should be given a higher priority for enforcing social distancing measures. CLINICALTRIAL", "qid": 10, "docid": "3nanf73b", "rank": 22, "score": 12.251899719238281}, {"content": "Title: Impact of Social Distancing Measures on COVID-19 Healthcare Demand in Central Texas Content: A novel coronavirus (SARS-CoV-2) emerged in Wuhan, China in late 2019 and rapidly spread worldwide. In the absence of effective antiviral drugs and vaccines, well-targeted social distancing measures are essential for mitigating the COVID-19 pandemic, reducing strain on local health systems, and preventing mortality. Here, we provide a quantitative assessment of the efficacy of social distancing to slow COVID-19 transmission and reduce hospital surge, depending on the timing and extent of the measures imposed for a metropolitan region and its health care systems. We built a granular mathematical model of COVID-19 transmission that incorporated age-specific and risk-stratified heterogeneity, estimates for the transmission, and severity of COVID-19 using current best evidence. We performed thousands of stochastic simulations of COVID-19 transmission in the Austin-Round Rock Metropolitan Area to project the impact of school closures coupled with social distancing measures that were estimated to reduce non-household contacts by 0%, 25%, 50%, 75% or 90%. We compare early versus late implementation and estimate the number of COVID-19 hospitalizations, ICU patients, ventilator needs and deaths through mid-August, 2020. We queried local emergency services and hospital systems to estimate total hospital bed, ICU, and ventilator capacity for the region. We expected COVID-19 hospital beds and ICU requirements would surpass local capacity by mid-May if no intervention was taken. Assuming a four-day epidemic doubling time, school closures alone would be expected to reduce peak hospitalizations by only 18% and cumulative deaths by less than 3%. Immediate social distancing measures that reduced non-household contacts by over 75%, such as stay-at-home orders and closing of non-essential businesses, would be required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. Peak ICU bed demand prior to mid August 2020 would be expected to be reduced from 2,121 (95% CI: 2,018-2,208) with no intervention to 698 (95% CI: 204-1,100) with 75% social distancing and 136 (95% CI: 38-308) with 90% social distancing; current ICU bed capacity was estimated at 680. A two-week delay in implementation of such measures is projected to accelerate a local ICU bed shortage by four weeks. School closures alone hardly impact the epidemic curve. Immediate social distancing measures that reduce non-household contacts by over 75% were required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. These findings helped inform the Stay Home-Work Safe order enacted by the city of Austin, Texas on March 24, 2020 as a means of mitigating the emerging COVID-19 epidemic.", "qid": 10, "docid": "n0nch8he", "rank": 23, "score": 12.245499610900879}, {"content": "Title: On the impact of early non-pharmaceutical interventions as containment strategies against the COVID-19 pandemic Content: Background The novel coronavirus SARS-CoV-2 (COVID-19) emerged in December 2019 in Wuhan, China and has spread since then to around 210 countries and territories by April 2020. Consequently, countries have adopted physical distance measures in an attempt to mitigate the uncontrolled spread of the virus. A critical question for policymakers to inform evidence-based practice is if and how physical distance measures slowed the propagation of COVID-19 in the early phase of the pandemic. Methods This study aims to quantify the effects of physical distance mitigation measures on the propagation of the COVID-19 pandemic. Data from John Hopkins University on confirmed cases and testing data from the Our World in Data were used in an interrupted time series analysis to estimate the effects of physical distance measures on the growth rates of the pandemic in 12 countries of Asia, Africa, and Europe. Findings We found that physical distance measures produced a significant decrease in the growth rates of the COVID-19 pandemic in five countries (Austria, Belgium, Italy, Malaysia, and South Korea). The test-positivity rate was significant in understanding the slowing growth rate of COVID-19 cases caused by the mitigation measures, as it provides important context that is missing from analysis based only on confirmed case data. Interpretation Physical distance interventions effectively slowed the progression of the COVID-19 pandemic. The results of this study could inform infectious disease mitigation policies based on physical distance measures by quantifying the differential health outcomes of a pandemic with and without physical distance interventions.", "qid": 10, "docid": "c0i11t0a", "rank": 24, "score": 12.115099906921387}, {"content": "Title: The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19 Content: We examine the net benefits of social distancing to slow the spread of COVID-19 in USA. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit\u2013cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed.", "qid": 10, "docid": "vfnpeuzr", "rank": 25, "score": 12.081999778747559}, {"content": "Title: Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility - Four U.S. Metropolitan Areas, February 26-April 1, 2020. Content: Community mitigation activities (also referred to as nonpharmaceutical interventions) are actions that persons and communities can take to slow the spread of infectious diseases. Mitigation strategies include personal protective measures (e.g., handwashing, cough etiquette, and face coverings) that persons can use at home or while in community settings; social distancing (e.g., maintaining physical distance between persons in community settings and staying at home); and environmental surface cleaning at home and in community settings, such as schools or workplaces. Actions such as social distancing are especially critical when medical countermeasures such as vaccines or therapeutics are not available. Although voluntary adoption of social distancing by the public and community organizations is possible, public policy can enhance implementation. The CDC Community Mitigation Framework (1) recommends a phased approach to implementation at the community level, as evidence of community spread of disease increases or begins to decrease and according to severity. This report presents initial data from the metropolitan areas of San Francisco, California; Seattle, Washington; New Orleans, Louisiana; and New York City, New York* to describe the relationship between timing of public policy measures, community mobility (a proxy measure for social distancing), and temporal trends in reported coronavirus disease 2019 (COVID-19) cases. Community mobility in all four locations declined from February 26, 2020 to April 1, 2020, decreasing with each policy issued and as case counts increased. This report suggests that public policy measures are an important tool to support social distancing and provides some very early indications that these measures might help slow the spread of COVID-19.", "qid": 10, "docid": "16t5rs6j", "rank": 26, "score": 12.075900077819824}, {"content": "Title: Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility - Four U.S. Metropolitan Areas, February 26-April 1, 2020 Content: Community mitigation activities (also referred to as nonpharmaceutical interventions) are actions that persons and communities can take to slow the spread of infectious diseases. Mitigation strategies include personal protective measures (e.g., handwashing, cough etiquette, and face coverings) that persons can use at home or while in community settings; social distancing (e.g., maintaining physical distance between persons in community settings and staying at home); and environmental surface cleaning at home and in community settings, such as schools or workplaces. Actions such as social distancing are especially critical when medical countermeasures such as vaccines or therapeutics are not available. Although voluntary adoption of social distancing by the public and community organizations is possible, public policy can enhance implementation. The CDC Community Mitigation Framework (1) recommends a phased approach to implementation at the community level, as evidence of community spread of disease increases or begins to decrease and according to severity. This report presents initial data from the metropolitan areas of San Francisco, California; Seattle, Washington; New Orleans, Louisiana; and New York City, New York* to describe the relationship between timing of public policy measures, community mobility (a proxy measure for social distancing), and temporal trends in reported coronavirus disease 2019 (COVID-19) cases. Community mobility in all four locations declined from February 26, 2020 to April 1, 2020, decreasing with each policy issued and as case counts increased. This report suggests that public policy measures are an important tool to support social distancing and provides some very early indications that these measures might help slow the spread of COVID-19.", "qid": 10, "docid": "41d7343o", "rank": 27, "score": 12.075899124145508}, {"content": "Title: The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control Content: Non-pharmaceutical interventions to combat COVID-19 transmission have worked to slow the spread of the epidemic but can have high socio-economic costs. It is critical we understand the efficacy of non-pharmaceutical interventions to choose a safe exit strategy. Many current models are not suitable for assessing exit strategies because they do not account for epidemic resurgence when social distancing ends prematurely (e.g., statistical curve fits) nor permit scenario exploration in specific locations. We developed an SEIR-type mechanistic epidemiological model of COVID-19 dynamics to explore temporally variable non-pharmaceutical interventions. We provide an interactive tool and code to estimate the transmission parameter, \u03b2, and the effective reproduction number, [Formula: see text]. We fit the model to Santa Clara County, California, where an early epidemic start date and early shelter-in-place orders could provide a model for other regions. As of April 22, 2020, we estimate an R(E) of 0.982 (95% CI: 0.849 \u2013 1.107) in Santa Clara County. After June 1 (the end-date for Santa Clara County shelter-in-place as of April 27), we estimate a shift to partial social distancing, combined with rigorous testing and isolation of symptomatic individuals, is a viable alternative to indefinitely maintaining shelter-in-place. We also estimate that if Santa Clara County had waited one week longer before issuing shelter-in-place orders, 95 additional people would have died by April 22 (95% CI: 7 \u2013 283). Given early life-saving shelter-in-place orders in Santa Clara County, longer-term moderate social distancing and testing and isolation of symptomatic individuals have the potential to contain the size and toll of the COVID-19 pandemic in Santa Clara County, and may be effective in other locations.", "qid": 10, "docid": "oqq92ke1", "rank": 28, "score": 11.971099853515625}, {"content": "Title: A Vision-based Social Distancing and Critical Density Detection System for COVID-19 Content: Social distancing has been proven as an effective measure against the spread of the infectious COronaVIrus Disease 2019 (COVID-19). However, individuals are not used to tracking the required 6-feet (2-meters) distance between themselves and their surroundings. An active surveillance system capable of detecting distances between individuals and warning them can slow down the spread of the deadly disease. Furthermore, measuring social density in a region of interest (ROI) and modulating inflow can decrease social distancing violation occurrence chance. On the other hand, recording data and labeling individuals who do not follow the measures will breach individuals' rights in free-societies. Here we propose an Artificial Intelligence (AI) based real-time social distancing detection and warning system considering four important ethical factors: (1) the system should never record/cache data, (2) the warnings should not target the individuals, (3) no human supervisor should be in the detection/warning loop, and (4) the code should be open-source and accessible to the public. Against this backdrop, we propose using a monocular camera and deep learning-based real-time object detectors to measure social distancing. If a violation is detected, a non-intrusive audio-visual warning signal is emitted without targeting the individual who breached the social distancing measure. Also, if the social density is over a critical value, the system sends a control signal to modulate inflow into the ROI. We tested the proposed method across real-world datasets to measure its generality and performance. The proposed method is ready for deployment, and our code is open-sourced.", "qid": 10, "docid": "gi6bzymv", "rank": 29, "score": 11.95930004119873}, {"content": "Title: Protocol for an Observational Study on the Effects of Social Distancing on Influenza-Like Illness and COVID-19 Content: The novel coronavirus disease (COVID-19) is a highly contagious respiratory disease that was first detected in Wuhan, China in December 2019, and has since spread around the globe, claiming more than 69,000 lives by the time this protocol is written. It has been widely acknowledged that the most effective public policy to mitigate the pandemic is \\emph{social and physical distancing}: keeping at least six feet away from people, working from home, closing non-essential businesses, etc. There have been a lot of anecdotal evidences suggesting that social distancing has a causal effect on disease mitigation; however, few studies have investigated the effect of social distancing on disease mitigation in a transparent and statistically-sound manner. We propose to perform an optimal non-bipartite matching to pair counties with similar observed covariates but vastly different average social distancing scores during the first week (March 16th through Match 22nd) of President's \\emph{15 Days to Slow the Spread} campaign. We have produced a total of $302$ pairs of two U.S. counties with good covariate balance on a total of $16$ important variables. Our primary outcome will be the average observed illness collected by Kinsa Inc. two weeks after the intervention period. Although the observed illness does not directly measure COVID-19, it reflects a real-time aspect of the pandemic, and unlike confirmed cases, it is much less confounded by counties' testing capabilities. We also consider observed illness three weeks after the intervention period as a secondary outcome. We will test a proportional treatment effect using a randomization-based test with covariance adjustment and conduct a sensitivity analysis.", "qid": 10, "docid": "3aaw7toy", "rank": 30, "score": 11.948800086975098}, {"content": "Title: Spread of Covid-19 in the United States is controlled Content: As of May 1, 2020, the number of cases of Covid-19 in the US passed 1,062,446, interventions to slow down the spread of Covid-19 curtailed most social activities. Meanwhile, an economic crisis and resistance to the strict intervention measures are rising. Some researchers proposed intermittent social distancing that may drive the outbreak of Covid-19 into 2022. Questions arise about whether we should maintain or relax quarantine measures. We developed novel artificial intelligence and causal inference integrated methods for real-time prediction and control of nonlinear epidemic systems. We estimated that the peak time of the Covid-19 in the US would be April 24, 2020 and its outbreak in the US will be over by the end of July and reach 1,551,901 cases. We evaluated the impact of relaxing the current interventions for reopening economy on the spread of Covid-19. We provide tools for balancing the risks of workers and reopening economy.", "qid": 10, "docid": "tusqf260", "rank": 31, "score": 11.948799133300781}, {"content": "Title: DOUBLE POWER LAW FOR COVID-19: PREDICTION OF NEW CASES AND DEATH RATES IN ITALY AND SPAIN Content: The novel corona virus SARS-CoV-2 appeared at the end of 2019, spreading rapidly and causing a severe respiratory syndrome (COVID-19) with high mortality (2-5%). Until a vaccine or therapy is found, the most effective method of prophylaxis has been to minimize transmission via rigorous social distancing and seclusion of all but essential workers. Such measures, implemented at different times and to varying degrees worldwide, have reduced the rate of transmission compared with early phases of the pandemic, resulting in flattening of the curve followed by a gradual reduction in mortality after >6 weeks of rigorous social distancing measures. The cost of rigorous social distancing has been seen in radically reduced economic activity, job losses, disruption of schooling and social institutions. A key question facing policy makers and individuals is when to resume normal economic and social activity in the face of persistent community transmission of SARS-CoV-2 . To help address this question, we have developed a model that accurately describes the entire transmission and mortality curves in Italy and Spain, two hard-hit countries that have maintained severe social distancing measures for over 2 months. Our model quantitatively describes the rapid rise and slow decay of new cases and deaths observed under stringent social distancing (the long tail effect). We predict that even when social distancing is rigorously maintained, the number of COVID-19 deaths after peak mortality may be 2-3 times larger than the total number of deaths up to the peak. Our model has important policy implications for countries currently debating how to ease social distancing measures.", "qid": 10, "docid": "zox6efyn", "rank": 32, "score": 11.910699844360352}, {"content": "Title: Defining Facets of Social Distancing during the COVID-19 Pandemic: Twitter Analysis Content: Social distancing has been one of the primary mitigation strategies in the United States to control the spread of novel coronavirus disease (COVID-19) and can be viewed as a multi-faceted public health measure. Using Twitter data, we aim to (1) define and quantify the prevalence and evolution of facets of social distancing during the COVID-19 pandemic in the US in a spatiotemporal context and (2) examine the most amplified tweets among social distancing facets. We analyzed a total of 259,529 unique tweets containing \"coronavirus\" from 115,485 unique users between January 23, 2020 and March 24, 2020 that were identified by the Twitter API as English and U.S.-based. Tweets containing specified keywords (determined a priori) were grouped into six social distancing facets: implementation, purpose, social disruption, adaptation, positive emotions, and negative emotions. Tweets about social disruptiveness were most retweeted, and implementation tweets were most favorited. Social distancing tweets became overall more prevalent in the U.S. from late January to March but were not geographically uniform. In January and February, facets of social distancing appeared in Los Angeles, San Francisco, and Seattle, which were among the first cities impacted by the COVID-19 outbreak. Tweets related to the \"implementation\" and \"negative emotions\" facets of social distancing largely dominated in combination with topics of \"social disruption\" and \"adaptation\", albeit to a lesser degree. Social distancing can be defined in terms of facets that respond and represent certain moments and events in a pandemic, including travel restrictions and rising COVID-19 case counts. For example, in February, Miami, FL had a low volume of social distancing tweets but grew in March which corresponded with the rise of COVID-19 cases in the city. This suggests that overall volume of social distancing tweets can reflect the relative case count in respective locations.", "qid": 10, "docid": "jtamxl3c", "rank": 33, "score": 11.84529972076416}, {"content": "Title: Agile Requirements Engineering and Software Planning for a Digital Health Platform to Engage the Effects of Isolation Caused by Social Distancing: Case Study Content: BACKGROUND: Social distancing and shielding measures have been put in place to reduce social interaction and slow the transmission of the coronavirus disease (COVID-19). For older people, self-isolation presents particular challenges for mental health and social relationships. As time progresses, continued social distancing could have a compounding impact on these concerns. OBJECTIVE: This project aims to provide a tool for older people and their families and peers to improve their well-being and health during and after regulated social distancing. First, we will evaluate the tool's feasibility, acceptability, and usability to encourage positive nutrition, enhance physical activity, and enable virtual interaction while social distancing. Second, we will be implementing the app to provide an online community to assist families and peer groups in maintaining contact with older people using goal setting. Anonymized data from the app will be aggregated with other real-world data sources to develop a machine learning algorithm to improve the identification of patients with COVID-19 and track for real time use by health systems. METHODS: Development of this project is occurring at the time of publication, and therefore, a case study design was selected to provide a systematic means of capturing software engineering in progress. The app development framework for software design was based on agile methods. The evaluation of the app's feasibility, acceptability and usability shall be conducted using Public Health England's guidance on evaluating digital health products, Bandura's model of health promotion, the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework and the Nonadoption, Abandonment and Challenges to the Scale-up, Spread and Suitability (NASSS) framework. RESULTS: Making use of a pre-existing software framework for health behavior change, a proof of concept was developed, and a multistage app development and deployment for the solution was created. Grant submissions to fund the project and study execution have been sought at the time of publication, and prediscovery iteration of the solution has begun. Ethical approval for a feasibility study design is being sought. CONCLUSIONS: This case study lays the foundations for future app development to combat mental and societal issues arising from social distancing measures. The app will be tested and evaluated in future studies to allow continuous improvement of the app. This novel contribution will provide an evidence-based exemplar for future app development in the space of social isolation and loneliness.", "qid": 10, "docid": "cranqd1y", "rank": 34, "score": 11.818900108337402}, {"content": "Title: Agile Requirements Engineering and Software Planning for a Digital Health Platform to Engage the Effects of Isolation Caused by Social Distancing: Case Study Content: BACKGROUND: Social distancing and shielding measures have been put in place to reduce social interaction and slow the transmission of the coronavirus disease (COVID-19). For older people, self-isolation presents particular challenges for mental health and social relationships. As time progresses, continued social distancing could have a compounding impact on these concerns. OBJECTIVE: This project aims to provide a tool for older people and their families and peers to improve their well-being and health during and after regulated social distancing. First, we will evaluate the tool\u2019s feasibility, acceptability, and usability to encourage positive nutrition, enhance physical activity, and enable virtual interaction while social distancing. Second, we will be implementing the app to provide an online community to assist families and peer groups in maintaining contact with older people using goal setting. Anonymized data from the app will be aggregated with other real-world data sources to develop a machine learning algorithm to improve the identification of patients with COVID-19 and track for real time use by health systems. METHODS: Development of this project is occurring at the time of publication, and therefore, a case study design was selected to provide a systematic means of capturing software engineering in progress. The app development framework for software design was based on agile methods. The evaluation of the app\u2019s feasibility, acceptability and usability shall be conducted using Public Health England's guidance on evaluating digital health products, Bandura\u2019s model of health promotion, the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework and the Nonadoption, Abandonment and Challenges to the Scale-up, Spread and Suitability (NASSS) framework. RESULTS: Making use of a pre-existing software framework for health behavior change, a proof of concept was developed, and a multistage app development and deployment for the solution was created. Grant submissions to fund the project and study execution have been sought at the time of publication, and prediscovery iteration of the solution has begun. Ethical approval for a feasibility study design is being sought. CONCLUSIONS: This case study lays the foundations for future app development to combat mental and societal issues arising from social distancing measures. The app will be tested and evaluated in future studies to allow continuous improvement of the app. This novel contribution will provide an evidence-based exemplar for future app development in the space of social isolation and loneliness.", "qid": 10, "docid": "oomxlk75", "rank": 35, "score": 11.818899154663086}, {"content": "Title: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Content: Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.", "qid": 10, "docid": "bsj7apol", "rank": 36, "score": 11.817399978637695}, {"content": "Title: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Content: Abstract Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.", "qid": 10, "docid": "nserrspn", "rank": 37, "score": 11.817399024963379}, {"content": "Title: Social Distancing Causally Impacts the Spread of SARS-CoV-2: A U.S. Nationwide Event Study Content: Background: To date, no study has examined the effectiveness of social distancing, while controlling for social mobility and social distancing restrictions in the United States. We utilize the quasi-experimental setting created by the nationwide protests precipitated by George Floyd's tragic death on May 25, 2020, to assess the causal impact of social distancing on the spread of SARS-CoV-2. Methods: Our sample period spans from January 22, 2020, to June 20, 2020, and consists of 474,422 county-days representing 3,142 counties from all 50 states and the District of Columbia. To assess the change in COVID-19 case counts following the protests, we employ a differences in differences estimation strategy in a multivariate setting, in which we control for social distancing restrictions and social mobility across counties. We also control for covariates that may influence COVID-19 transmission, and implement placebo tests using a Monte Carlo simulation. Findings: We document a country wide increase of over 3.06 cases per day, per 100,000 population, following the onset of the protests (95%CI: 2.47-3.65), and a further increase of 1.73 cases per day, per 100,000 population, in the counties in which the protests took place (95%CI: 0.59- 2.87). Relative to the week preceding the onset of the protests, this represents a 61.2% country wide increase in COVID-19 cases, and a further 34.6% increase in the protest counties. Interpretation: Our study documents a significant increase in COVID-19 case counts in counties that experienced a protest, and we conclude that social distancing practices causally impact the spread of SARS-CoV-2. The observed effect cannot be explained by changes in social distancing restrictions and social mobility, and placebo tests rule out the possibility that this finding is attributable to chance.", "qid": 10, "docid": "s74jgknw", "rank": 38, "score": 11.786700248718262}, {"content": "Title: Lay perspectives on social distancing and other official recommendations and regulations in the time of COVID-19: a qualitative study of social media posts Content: BACKGROUND: COVID-19 caused by a new form of coronavirus (SARS-CoV-2) first appeared in China end of 2019 and quickly spread to all counties of the world. To slow down the spread of the virus and to limit the pressure on the health care systems, different regulations and recommendations have been implemented by authorities, comprising amongst others the closure of all entertainment venues and social distancing. These measures have received mixed reactions, particularly from young individuals, with many not following available advice. Drawing on the information in social media discussion forums, the present study explores the reasons why people ignore the orders and recommendations of the authorities and why the authorities are unable to produce a shared sense of inclusion concerning protective measures against the COVID-19 outbreak. METHODS: Three open-access social media forums (Reddit, Twitter, and YouTube comments) were systematically searched with respect to COVID-19-related beliefs, attitudes, and behaviours of individuals. The data was retrieved in the first 3 weeks of March 2020. Qualitative document analysis and qualitative content analysis were used as the methodical approach. The data was reviewed by all authors and jointly interpreted to minimise inconsistencies. RESULTS: The study reveals that reasons such as information pollution on social media, the persistence of uncertainty about the rapidly spreading virus, the impact of the social environment on the individual, and fear of unemployment associated with inequality in the distribution of income lead people to ignore the orders and recommendations of the authorities. The findings suggest that government representatives and politicians could not produce a shared sense of inclusion concerning protective measures against the COVID-19 outbreak, due to not building trust among the public and taking concrete economic steps to satisfy them. CONCLUSION: In uncertain crises, transparency in the presentation of information and government policies emerge as influential determinants in creating social susceptibility and solidarity. The differences between social classes constitute one of the important factors that affect the decision-making mechanisms of individuals in determining the necessary steps to be undertaken in times of crisis.", "qid": 10, "docid": "35u70l6e", "rank": 39, "score": 11.781999588012695}, {"content": "Title: Senior Medical Students in the COVID\u201019 Response: An Opportunity to Be Proactive Content: On March 13th, the United States (US) declared the novel coronavirus (COVID-19) pandemic a national emergency. By March 18th , according to the Centers for Disease Control and Prevention, COVID-19 had spread to all 50 US states, with 7,038 cases and 97 deaths.1 The trajectory of cases mirrors that of Italy, where doctors are forced to consider who is more deserving of a ventilator.2 In response, social distancing measures are being promoted across the US in the hopes of slowing the growth in new cases, i.e. \"flattening the curve.\" This could maintain the demand for acute care within the healthcare system's capacity to treat.3 Travel has been curtailed, conferences and concerts cancelled, and schools and universities have moved students off campus and classes online. Medical schools are following suit, with added motivators. In canceling classes and rotations, medical schools hope to: promote social distancing, limit the risk of students contracting the virus, limit the number of healthcare workers who might spread the virus to unaffected patients, minimize the teaching burden on frontline providers, and preserve personal protective equipment (PPE) for essential personnel. These are logical reasons for removing students from hospitals. But, despite our best efforts, there may come a point in the US when, as is set to happen in Italy, medical demand outpaces medical capacity.2 If the same happens here, is there a plan in place for incorporating senior medical students into emergency relief efforts?", "qid": 10, "docid": "05jzxdy8", "rank": 40, "score": 11.781499862670898}, {"content": "Title: A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we suggest that pre-symptomatic transmission could be a significant driver of the infection spread. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.", "qid": 10, "docid": "swcq2wfl", "rank": 41, "score": 11.779000282287598}, {"content": "Title: Debate: COVID-19 and psychological well-being of children and adolescents in Italy Content: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.", "qid": 10, "docid": "8jvljcuh", "rank": 42, "score": 11.707799911499023}, {"content": "Title: Debate: COVID-19 and psychological well-being of children and adolescents in Italy. Content: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.", "qid": 10, "docid": "lgf0nwgx", "rank": 43, "score": 11.707798957824707}, {"content": "Title: Comparative Analysis of the Application of Behavioural Insights of 33 Worldwide Governments on the Landing Pages of their COVID-19 Official Websites and their Impact on the Growth Scale of the Pandemic Content: The COVID-19 crisis has seen over a third of the world population locked down and this article has sought to understand human behaviour in response to a historical and unprecedented global pandemic. Through the analysis 18 behavioural mechanisms present on the landing pages of the websites of 33 institutional governments from March 1st til May 1st 2020 compared to the WHO data on the number of COVID-19 cases and deaths per million for each country, the authors show that a behavioural consensus was observed across all 33 countries and that Individual and Social nudges had no impact. Whilst the decisions in essentially every country on Earth, were taken with the same aim: to limit population movements and social life, two aggravating factors of the spread of the virus, only the environmental nudges effectively helped slow the virus growth scale. The authors explain the rationale behind these results and suggest that people seek information beyond governmental websites that they generally mistrust. They further suggest using Scientists as role models to encourage governmental website's traffic and designing recursive nudges to increase the impact of individual and social interventions. Together with the new phases of the spread of the virus will come new rules and guidance. Public health policies need to address behavioural change of the population on a global scale in a more targeted manner and it is hoped that this paper will provide some insight on how to do so.", "qid": 10, "docid": "nxj2gqx6", "rank": 44, "score": 11.694299697875977}, {"content": "Title: Challenges in control of Covid-19: short doubling time and long delay to effect of interventions Content: Early assessments of the spreading rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but more reliable inferences can now be made. Here, we estimate from European data that COVID-19 cases are expected to double initially every three days, until social distancing interventions slow this growth, and that the impact of such measures is typically only seen nine days - i.e. three doubling times - after their implementation. We argue that such temporal patterns are more critical than precise estimates of the basic reproduction number for initiating interventions. This observation has particular implications for the low-and middle-income countries currently in the early stages of their local epidemics.", "qid": 10, "docid": "k5q07y4b", "rank": 45, "score": 11.667400360107422}, {"content": "Title: Challenges in control of Covid-19: short doubling time and long delay to effect of interventions Content: Early assessments of the spreading rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but more reliable inferences can now be made. Here, we estimate from European data that COVID-19 cases are expected to double initially every three days, until social distancing interventions slow this growth, and that the impact of such measures is typically only seen nine days - i.e. three doubling times - after their implementation. We argue that such temporal patterns are more critical than precise estimates of the basic reproduction number for initiating interventions. This observation has particular implications for the low- and middle-income countries currently in the early stages of their local epidemics.", "qid": 10, "docid": "s0awhe4y", "rank": 46, "score": 11.667399406433105}, {"content": "Title: SHELTER IN PLACE ORDER CONTAINED COVID-19 GROWTH RATE IN GREECE Content: Background: The Greek authorities implemented the strong social distancing measures within the first few weeks after the first confirmed case of the virus to curtail the COVID-19 growth rate. Objectives: To estimate the effect of the two-stage strong social distancing measures, the closure of all non-essential shopping centers and businesses on March 16 and the shelter in place orders (SIPOs) on March 23 on the COVID-19 growth rate in Greece Methods: We obtained data on COVID-19 cases in Greece from February 26th through May 4th from publicly available sources. An interrupted time-series regression analysis was used to estimate the effect of the measures on the exponential growth of confirmed COVID-19 cases, controlling for the number of daily testing, and weekly fixed-effects. Results: The growth rate of the COVID-19 cases in the pre-policies implementation period was positive as expected (p=0.003). Based on the estimates of the interrupted time-series, our results indicate that the SIPO on March 23 significantly slowed the growth rate of COVID-19 in Greece (p=0.04). However, we did not find evidence on the effectiveness of standalone and partial measures such as the non-essential business closures implemented on March 16 on the COVID-19 spread reduction. Discussion: The combined social distancing measures implemented by the Greek authorities within the first few weeks after the first confirmed case of the virus reduced the COVID-19 growth rate. These findings provide evidence and highlight the effectiveness of these measures to flatten the curve and to slow the spread of the virus.", "qid": 10, "docid": "tkajjrri", "rank": 47, "score": 11.637499809265137}, {"content": "Title: Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States Content: Coronavirus disease 2019 (Covid-19) has devastated global populations and has had a large impact in the United States with the number of infections and deaths growing exponentially. Using a smooth generalized additive model with quasipoisson counts for total infections and deaths, we developed a county-level predictive model that included population demographics, social characteristics, social distancing, and testing data. This model strongly predicted the actual US distribution of Covid-19, accounting for 94.8% of spatial-temporal variation in total infections and 99.3% in Covid-19 related fatalities from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans had a higher number of confirmed infections adjusted for county population. Social distancing measured by the change in the rate of human encounter per km2 relative to pre-covid-19 national average was associated with slower rate of Covid-19 infections, whereas higher testing was associated with higher number of infections. The number of people infected was increasing, however, the rate of increase in new infections was starting to show signs of plateauing starting from the second week of April. Our model projects 2.11 million people to test positive for Covid-19 and 122,951 fatalities by June 1, 2020. Importantly, our model suggests strong social differences in the infections and deaths across US communities, and inequities in areas with larger African American minorities and higher poverty index expected to show higher rates of Covid-19 infections and deaths. Preventive steps including social distancing and community closures have been a cornerstone in stopping the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in the disease transmission is essential to understand current disease distribution, predict future distribution, and plan additional preventive steps.", "qid": 10, "docid": "6wqxcshu", "rank": 48, "score": 11.627599716186523}, {"content": "Title: Effectiveness and Compliance to Social Distancing During COVID-19 Content: In the absence of pharmaceutical interventions to curb the spread of COVID-19, countries relied on a number of nonpharmaceutical interventions to fight the first wave of the pandemic. The most prevalent one has been stay-at-home orders, whose the goal is to limit the physical contact between people, which consequently will reduce the number of secondary infections generated. In this work, we use a detailed set of mobility data to evaluate the impact that these interventions had on alleviating the spread of the virus in the US as measured through the COVID-19-related deaths. To establish this impact, we use the notion of Granger causality between two time-series. We show that there is a unidirectional Granger causality, from the median percentage of time spent daily at home to the daily number of COVID-19-related deaths with a lag of 2 weeks. We further analyze the mobility patterns at the census block level to identify which parts of the population might encounter difficulties in adhering and complying with social distancing measures. This information is important, since it can consequently drive interventions that aim at helping these parts of the population.", "qid": 10, "docid": "ibrrr546", "rank": 49, "score": 11.614999771118164}, {"content": "Title: A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing Content: Abstract Background: The ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required. Methods: Using COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia. Findings: In countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases. Interpretation: Modelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased.", "qid": 10, "docid": "t7p2j504", "rank": 50, "score": 11.585200309753418}, {"content": "Title: Decline in global COVID-19 transmission Content: We analyzed COVID-19 data through April 16, 2020 using a partially observed Markov process. Our method uses a hybrid deterministic and stochastic formalism that allows for time variable transmission rates and detection probabilities. The model was fit using iterated particle filtering to case count and death count time series from 51 countries. We found evidence for a declining transmission rate in 42 of the 51 examined countries. Of those 42 countries 34 have significant evidence for subcritical transmission rates, although the decline in new cases are relatively slow compared to the initial growth rates. This suggests that global scale social distancing efforts to slow the spread of COVID-19 are effective although they need to be strengthened in many regions and maintained in others to avoid further resurgence of COVID-19. The slow decline also suggests alternative strategies to control the virus are needed before social distancing efforts are partially relaxed.", "qid": 10, "docid": "9o2tk4x5", "rank": 51, "score": 11.549300193786621}, {"content": "Title: Compliance and containment in social distancing: mathematical modeling of COVID-19 across townships Content: In the early development of COVID-19, large-scale preventive measures, such as border control and air travel restrictions, were implemented to slow international and domestic transmissions. When these measures were in full effect, new cases of infection would be primarily induced by community spread, such as the human interaction within and between neighboring cities and towns, which is generally known as the meso-scale. Existing studies of COVID-19 using mathematical models are unable to accommodate the need for meso-scale modeling, because of the unavailability of COVID-19 data at this scale and the different timings of local intervention policies. In this respect, we propose a meso-scale mathematical model of COVID-19 using town-level infection data in the state of Connecticut. We consider the spatial interaction in terms of the inter-town travel in the model. Based on the developed model, we evaluated how different strengths of social distancing policy enforcement may impact future epidemic curves based on two evaluative metrics: compliance and containment. The developed model and the simulation results will establish the foundation for community-level assessment and better preparation for COVID-19.", "qid": 10, "docid": "la8unax6", "rank": 52, "score": 11.4975004196167}, {"content": "Title: A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we reveal that pre-symptomatic transmission accelerates the onset of the exponential growth of cases. After that, we demonstrate that the persistence of SARS-CoV-2 on hard surfaces determines the number of cases reached during the peak of the epidemic. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.", "qid": 10, "docid": "ghwyrew1", "rank": 53, "score": 11.479700088500977}, {"content": "Title: From predictions to prescriptions: A data-driven response to COVID-19 Content: The COVID-19 pandemic has created unprecedented challenges worldwide. Strained healthcare providers make difficult decisions on patient triage, treatment and care management on a daily basis. Policy makers have imposed social distancing measures to slow the disease, at a steep economic price. We design analytical tools to support these decisions and combat the pandemic. Specifically, we propose a comprehensive data-driven approach to understand the clinical characteristics of COVID-19, predict its mortality, forecast its evolution, and ultimately alleviate its impact. By leveraging cohort-level clinical data, patient-level hospital data, and census-level epidemiological data, we develop an integrated four-step approach, combining descriptive, predictive and prescriptive analytics. First, we aggregate hundreds of clinical studies into the most comprehensive database on COVID-19 to paint a new macroscopic picture of the disease. Second, we build personalized calculators to predict the risk of infection and mortality as a function of demographics, symptoms, comorbidities, and lab values. Third, we develop a novel epidemiological model to project the pandemic's spread and inform social distancing policies. Fourth, we propose an optimization model to re-allocate ventilators and alleviate shortages. Our results have been used at the clinical level by several hospitals to triage patients, guide care management, plan ICU capacity, and re-distribute ventilators. At the policy level, they are currently supporting safe back-to-work policies at a major institution and equitable vaccine distribution planning at a major pharmaceutical company, and have been integrated into the US Center for Disease Control's pandemic forecast.", "qid": 10, "docid": "480ncsft", "rank": 54, "score": 11.440799713134766}, {"content": "Title: From predictions to prescriptions: A data-drivenresponse to COVID-19 Content: The COVID-19 pandemic has created unprecedented challenges worldwide. Strained healthcare providers make difficult decisions on patient triage, treatment and care management on a daily basis. Policy makers have imposed social distancing measures to slow the disease, at a steep economic price. We design analytical tools to support these decisions and combat the pandemic. Specifically, we propose a comprehensive data-driven approach to understand the clinical characteristics of COVID-19, predict its mortality, forecast its evolution, and ultimately alleviate its impact. By leveraging cohort-level clinical data, patient-level hospital data, and census-level epidemiological data, we develop an integrated four-step approach, combining descriptive, predictive and prescriptive analytics. First, we aggregate hundreds of clinical studies into the most comprehensive database on COVID-19 to paint a new macroscopic picture of the disease. Second, we build personalized calculators to predict the risk of infection and mortality as a function of demographics, symptoms, comorbidities, and lab values. Third, we develop a novel epidemiological model to project the pandemic's spread and inform social distancing policies. Fourth, we propose an optimization model to reallocate ventilators and alleviate shortages. Our results have been used at the clinical level by several hospitals to triage patients, guide care management, plan ICU capacity, and re-distribute ventilators. At the policy level, they are currently supporting safe back-to-work policies at a major institution and equitable vaccine distribution planning at a major pharmaceutical company, and have been integrated into the US Center for Disease Control's pandemic forecast.", "qid": 10, "docid": "a5ngjuyz", "rank": 55, "score": 11.44079875946045}, {"content": "Title: Impact of policy interventions and social distancing on SARS-CoV-2 transmission in the United States Content: Background: Policymakers have employed various non-pharmaceutical interventions (NPIs) such as stay-at-home orders and school closures to limit the spread of Coronavirus disease (COVID-19). However, these measures are not without cost, and careful analysis is critical to quantify their impact on disease spread and guide future initiatives. This study aims to measure the impact of NPIs on the effective reproductive number (Rt) and other COVID-19 outcomes in U.S. states. Methods: In order to standardize the stage of disease spread in each state, this study analyzes the weeks immediately after each state reached 500 cases. The primary outcomes were average Rt in the week following 500 cases and doubling time from 500 to 1000 cases. Linear and logistic regressions were performed in R to assess the impact of various NPIs while controlling for population density, GDP, and certain health metrics. This analysis was repeated for deaths with doubling time from 50 to 100 deaths and included several healthcare infrastructure control variables. Results: States that had a stay-at-home order in place at the time of their 500th case are associated with lower average Rt the following week compared to states without a stay-at-home order (p < 0.001) and are significantly less likely to have an Rt>1 (OR 0.07, 95% CI 0.01 to 0.37, p = 0.004). These states also experienced a significantly longer doubling time from 500 to 1000 cases (HR 0.35, 95% CI 0.17 to 0.72, p = 0.004). States in the highest quartile of average time spent at home were also slower to reach 1000 cases than those in the lowest quartile (HR 0.18, 95% CI 0.06 to 0.53, p = 0.002). Discussion: Few studies have analyzed the effect of statewide stay-at-home orders, school closures, and other social distancing measures in the U.S., which has faced the largest COVID-19 case burden. States with stay-at-home orders have a 93% decrease in the odds of having a positive Rt at a standardized point in disease burden. States that plan to scale back such measures should carefully monitor transmission metrics. Key words: COVID-19, SARS-CoV-2, Coronavirus, Public Policy, Social Distancing, Non-pharmaceutical Interventions, Stay-at-home Order, Shelter-in-place.", "qid": 10, "docid": "1roqno6p", "rank": 56, "score": 11.417200088500977}, {"content": "Title: Adoption and impact of non-pharmaceutical interventions for COVID-19 Content: Background: Several non-pharmaceutical interventions (NPIs) have been implemented across the world to control the coronavirus disease (COVID-19) pandemic. Social distancing (SD) interventions applied so far have included school closures, remote working and quarantine. These measures have been shown to have large impacts on pandemic influenza transmission. However, there has been comparatively little examination of such measures for COVID-19. Methods: We examined the existing literature, and collated data, on implementation of NPIs to examine their effects on the COVID-19 pandemic so far. Data on NPIs were collected from official government websites as well as from media sources. Results: Measures such as travel restrictions have been implemented in multiple countries and appears to have slowed the geographic spread of COVID-19 and reduced initial case numbers. We find that, due to the relatively sparse information on the differences with and without interventions, it is difficult to quantitatively assess the efficacy of many interventions. Similarly, whilst the comparison to other pandemic diseases such as influenza can be helpful, there are key differences that could affect the efficacy of similar NPIs. Conclusions: The timely implementation of control measures is key to their success and must strike a balance between early enough application to reduce the peak of the epidemic and ensuring that they can be feasibly maintained for an appropriate duration. Such measures can have large societal impacts and they need to be appropriately justified to the population. As the pandemic of COVID-19 progresses, quantifying the impact of interventions will be a vital consideration for the appropriate use of mitigation strategies.", "qid": 10, "docid": "hipujblu", "rank": 57, "score": 11.390800476074219}, {"content": "Title: Tracking COVID-19 by Tracking Infectious Trajectories Content: Nowadays, the coronavirus pandemic has and is still causing large numbers of deaths and infected people. Although governments all over the world have taken severe measurements to slow down the virus spreading (e.g., travel restrictions, suspending all sportive, social, and economic activities, quarantines, social distancing, etc.), a lot of persons have died and a lot more are still in danger. Indeed, a recently conducted study~\\cite{ref2} has reported that 79\\% of the confirmed infections in China were caused by undocumented patients who had no symptoms. In the same context, in numerous other countries, since coronavirus takes several days before the emergence of symptoms, it has also been reported that the known number of infections is not representative of the real number of infected people (the actual number is expected to be much higher). That is to say, asymptomatic patients are the main factor behind the large quick spreading of coronavirus and are also the major reason that caused governments to lose control over this critical situation. To contribute to remedying this global pandemic, in this paper, we propose an IoT (Internet of Things) investigation system that was specifically designed to spot both undocumented patients and infectious places. The goal is to help the authorities to disinfect high-contamination sites and confine persons even if they have no apparent symptoms. The proposed system also allows determining all persons who had close contact with infected or suspected patients. Consequently, rapid isolation of suspicious cases and more efficient control over any pandemic propagation can be achieved.", "qid": 10, "docid": "baheh8i5", "rank": 58, "score": 11.32979965209961}, {"content": "Title: Age-structured impact of social distancing on the COVID-19 epidemic in India Content: The outbreak of the novel coronavirus, COVID-19, has been declared a pandemic by the WHO. The structures of social contact critically determine the spread of the infection and, in the absence of vaccines, the control of these structures through large-scale social distancing measures appears to be the most effective means of mitigation. Here we use an age-structured SIR model with social contact matrices obtained from surveys and Bayesian imputation to study the progress of the COVID-19 epidemic in India. The basic reproductive ratio R0 and its time-dependent generalization are computed based on case data, age distribution and social contact structure. The impact of social distancing measures - workplace non-attendance, school closure, lockdown - and their efficacy with durations are then investigated. A three-week lockdown is found insufficient to prevent a resurgence and, instead, protocols of sustained lockdown with periodic relaxation are suggested. Forecasts are provided for the reduction in age-structured morbidity and mortality as a result of these measures. Our study underlines the importance of age and social contact structures in assessing the country-specific impact of mitigatory social distancing.", "qid": 10, "docid": "xbuypaf6", "rank": 59, "score": 11.328800201416016}, {"content": "Title: Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis Content: Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "qid": 10, "docid": "po2c65nb", "rank": 60, "score": 11.324399948120117}, {"content": "Title: Sustaining Social Distancing Policies to Prevent a Dangerous Second Peak of COVID-19 Outbreak Content: Governments around the world have enacted strict social distancing policies in order to slow the spread of COVID-19. The next step is figuring out when to relax these restrictions and to what degree. Our results predict potentially disastrous implications of ending these policies too soon, based on projections made from a Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model. Even when infection rates appear to be slowing down or decreasing, prematurely returning to \"business as usual\" produces a severe second peak far worse than the first. Furthermore, such a second peak is made more likely when very severe restrictions are initially enacted. Only an appropriately measured and committed set of restrictions can appropriately control COVID-19 outbreak levels.", "qid": 10, "docid": "j1ma6r50", "rank": 61, "score": 11.264100074768066}, {"content": "Title: AN INTERACTIVE COVID-19 MOBILITY IMPACT AND SOCIAL DISTANCING ANALYSIS PLATFORM Content: The research team has utilized privacy-protected mobile device location data, integrated with COVID-19 case data and census population data, to produce a COVID-19 impact analysis platform that can inform users about the effects of COVID-19 spread and government orders on mobility and social distancing. The platform is being updated daily, to continuously inform decision-makers about the impacts of COVID-19 on their communities using an interactive analytical tool. The research team has processed anonymized mobile device location data to identify trips and produced a set of variables including social distancing index, percentage of people staying at home, visits to work and non-work locations, out-of-town trips, and trip distance. The results are aggregated to county and state levels to protect privacy and scaled to the entire population of each county and state. The research team are making their data and findings, which are updated daily and go back to January 1, 2020, for benchmarking, available to the public in order to help public officials make informed decisions. This paper presents a summary of the platform and describes the methodology used to process data and produce the platform metrics.", "qid": 10, "docid": "fmf3a7b8", "rank": 62, "score": 11.24779987335205}, {"content": "Title: Social distancing alters the clinical course of COVID-19 in young adults: A comparative cohort study Content: BACKGROUND: Social distancing and stringent hygiene seem effective in reducing the number of transmitted virus particles, and therefore the infectivity, of coronavirus disease 2019 (COVID-19) and could alter the mode of transmission of the disease. However, it is not known if such practices can change the clinical course in infected individuals. METHODS: We prospectively studied an outbreak of COVID-19 in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. We followed the number of infections in two spatially separated cohorts with almost identical baseline characteristics with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after implementation of stringent social distancing. RESULTS: Of the 354 soldiers infected prior to the implementation of social distancing, 30% fell ill from COVID-19. While no soldier in a group of 154, in which infections appeared after implementation of social distancing, developed COVID-19 despite the detection of viral RNA in the nose and virus-specific antibodies within this group. CONCLUSIONS: Social distancing not only can slow the spread of SARS-CoV-2 in a cohort of young, healthy adults but can also prevent the outbreak of COVID-19 while still inducing an immune response and colonizing nasal passages. Viral inoculum during infection or mode of transmission may be key factors determining the clinical course of COVID-19.", "qid": 10, "docid": "trn2deod", "rank": 63, "score": 11.2322998046875}, {"content": "Title: Model of a Testing-and-Quarantine Strategy to Slow-Down the COVID-19 Outbreak in Guadeloupe Content: Using a stochastic epidemic model explicitly considering the entire population of Guadeloupe (1), we explore the domain of solutions presenting an efficient slowing down of the COVID-19 epidemic spread during the post-containment period. The considered model parameters are the basic reproduction number R0 to simulate the effects of social distancing, the time delay {delta}TQ elapsed between the detection of a symptomatic person and her/his placement in quarantine to suppress her/his contagiousness, and the number Na of asymptomatic people tested positively and isolated. We show that acceptable solutions are obtained for a wide range of parameter values. Thanks to a good control of the initial epidemic spread resulting from an early containment and efficient communication by the sanitary and administrative authorities, the present situation corresponds to a pre-epidemic state. The most safe solutions are a combinations of social distancing, numerous testing to perform a systematic isolation of symptomatic patients and guided detection of asymptomatic people in the entourage of localised symptomatic patients.", "qid": 10, "docid": "5kv2j7nn", "rank": 64, "score": 11.225199699401855}, {"content": "Title: The COVID-19 Pandemic Confronts the Motivation Fallacy within Pulmonary Rehabilitation Programs. Content: Social distancing and quarantines have been implemented worldwide to reduce the spread of Coronavirus Disease (COVID-19). However, social distancing has had far-reaching health consequences, considering that the COVID-19 pandemic has exposed people to the hazard of physical inactivity and sedentary behavior. For patients with Chronic Obstructive Pulmonary Disease (COPD), which is one of the main diseases at risk for COVID-19, the impact is even greater since outpatient pulmonary rehabilitation (PR) programs are temporarily closed. More than ever, patients' behavior change to exercise calls for urgent debate. We propose a theoretical discussion in light of Self-Determination Theory, aiming to make PR a setting that supports autonomous forms of motivation. The scenario will not be changed in the short-term; but if other conditions hinder the development of PR in its most traditional form, the PR community will be better prepared to overcome the barriers to maintain physical exercise.", "qid": 10, "docid": "zp4xc5ma", "rank": 65, "score": 11.223099708557129}, {"content": "Title: Social distancing to slow the U.S. COVID-19 epidemic: an interrupted time-series analysis Content: Background: Social distancing measures to address the U.S. COVID-19 epidemic may have significant health, social, and economic impacts. Objective: To estimate the mean change in state-level COVID-19 epidemic growth before versus after the implementation of statewide social distancing measures. Design: Interrupted time-series analysis. Setting: United States. Measurements: Our primary exposure was time in relation to implementation of the first statewide social distancing measure. The pre-implementation period began 14 days prior to implementation and included up to 3 days after implementation to account for incubation. Post-implementation began 4 days after, up to and including March 30. Our primary outcome was the COVID-19 growth rate, calculated as the log of daily COVID-19 cases minus the log of daily COVID-19 cases on the prior day. Results: All states applied some form of statewide social distancing between March 10-27. The mean daily COVID-19 growth rate decreased beginning four days after implementation of the first statewide social distancing measures, by an additional 0.8% per day; 95% CI, -1.4% to -0.2%; P=0.002). This reduction corresponds to an increase in doubling time of the epidemic from 3.3 days (before) to 5.0 days (at 14 days after implementation). Limitations: Potential bias due to the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillovers across neighboring states. Conclusion: Statewide social distancing measures were associated with a decrease in U.S. COVID-19 epidemic growth. Based on the size of the epidemic at the time of implementation in each state, social distancing measures were associated with a decrease of 3,090 cases at 7 days, and 68,255 cases at 14 days, after implementation.", "qid": 10, "docid": "ls408b2b", "rank": 66, "score": 11.214099884033203}, {"content": "Title: Progression of COVID-19 in Indian States - Forecasting Endpoints Using SIR and Logistic Growth Models Content: COVID-19 has led to the most widespread public health crisis in recent history. The first case of the disease was detected in India on 31 January 2019, and confirmed cases stand at 74,281 as of 13 May 2020. Mathematical modeling can be utilized to forecast the final numbers as well as the endpoint of the disease in India and its states, as well as assess the impact of social distancing measures. In the present work, the Susceptible-Infected-Recovered (SIR) model and the Logistic Growth model have been implemented to predict the endpoint of COVID-19 in India as well as three states accounting for over 55% of the total cases - Maharashtra, Gujarat and Delhi. The results using the SIR model indicate that the disease will reach an endpoint in India on 12 September, while Maharashtra, Gujarat and Delhi will reach endpoints on 20 August, 30 July and 9 September respectively. Using the Logistic Regression model, the endpoint for India is predicted on 23 July, while that for Maharashtra, Gujarat and Delhi is 5 July, 23 June and 10 August respectively. It is also observed that the case numbers predicted by the SIR model are greater than those for the Logistic Growth model in each case. The results suggest that the lockdown enacted by the Government of India has had only a moderate impact on the spread of COVID-19, and emphasize the need for firm implementation of social distancing guidelines.", "qid": 10, "docid": "c35chwpz", "rank": 67, "score": 11.142200469970703}, {"content": "Title: \u2018What is Inconvenient for You is Life-saving for Me\u2019: How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 10, "docid": "3ly4f8dy", "rank": 68, "score": 11.140199661254883}, {"content": "Title: 'What is Inconvenient for You is Life-saving for Me': How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 10, "docid": "hwlr3qfz", "rank": 69, "score": 11.140198707580566}, {"content": "Title: Using VERA to explain the impact of social distancing on the spread of COVID-19 Content: COVID-19 continues to spread across the country and around the world. Current strategies for managing the spread of COVID-19 include social distancing. We present VERA, an interactive AI tool, that first enables users to specify conceptual models of the impact of social distancing on the spread of COVID-19. Then, VERA automatically spawns agent-based simulations from the conceptual models, and, given a data set, automatically fills in the values of the simulation parameters from the data. Next, the user can view the simulation results, and, if needed, revise the simulation parameters and run another experimental trial, or build an alternative conceptual model. We describe the use VERA to develop a SIR model for the spread of COVID-19 and its relationship with healthcare capacity.", "qid": 10, "docid": "p1jeiljo", "rank": 70, "score": 11.129400253295898}, {"content": "Title: Forecasting COVID 19 growth in India using Susceptible-Infected-Recovered (S.I.R) model Content: This work covers the analysis of the COVID 19 spread in different countries and dealing the main feature of COVID 19 growth, which is the spread due to the social-contact structure, which is governed by the parameter \\b{eta}. The dependency of this parameter \\b{eta} on the transmission level in society gives a sense of the effectiveness of the measures taken for social distancing. A separate algorithm is hardcoded in python using Scipy which learns the social-contact structure and gives a suitable value for \\b{eta}, which has a major impact on the outcome of the result. Forecasting for the epidemic spread in India was done, and it was found that the strictness at which social distancing in India is done, is insufficient for the growth of COVID 19.", "qid": 10, "docid": "9a131e0i", "rank": 71, "score": 11.120699882507324}, {"content": "Title: Modeling the dynamics of COVID19 spread during and after social distancing Content: Non-pharmaceutical intervention measures, such as social distancing, have so far been the only means to slow the spread of COVID19. In the United States, strict social distancing has resulted in different types infection dynamics. In some states, such as New York, extensive infection spread was followed by a pronounced decline of infection levels. In other states, such as California, less infection spread occurred before strict social distancing, and a different pattern was observed. Instead of a pronounced infection decline, a long-lasting plateau is evident, characterized by similar daily new infection levels. While these plateau dynamics cannot be readily reproduced with standard SIR infection models, we show that network models, in which individuals and their social contacts are explicitly tracked, can reproduce the plateau if network connections are cut due to social distancing measures. The reason is that in networks characterized by a degree of 2D spatial structure, infection tends to spread quadratically with time, but as edges are randomly removed, the infection spreads along nearly one-dimensional infection \"corridors\", resulting in plateau dynamics. Interestingly, the plateau dynamics are predicted to eventually transition into an infection decline phase without any further increase in social distancing measures. Additionally, the models suggest that a potential second wave becomes significantly less pronounced if social distancing is only relaxed once the dynamics have transitioned to the decline phase. The network models analyzed here allow us to interpret and reconcile different infection dynamics during social distancing observed in various US states.", "qid": 10, "docid": "0b6dsdct", "rank": 72, "score": 11.11989974975586}, {"content": "Title: Understanding Economic and Health Factors Impacting the Spread of COVID-19 Disease Content: The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely-populated areas. Aiming at bringing more light on key economic and public health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly-available COVID-19 datasets. The study had shown and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We have also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study has identified potential COVID-19 under-reporting traits as well as various economic factors that impact COVID-19 Diagnosis, Reporting, and Treatment. Based on the country clusters, we have also described the four disease development scenarios, which are tightly knit to country-level economic and public health factors. Finally, we have highlighted the potential limitation of reporting and measuring COVID-19 and provided recommendations on further in-depth quantitative research.", "qid": 10, "docid": "keaxietu", "rank": 73, "score": 11.118800163269043}, {"content": "Title: Public health interventions in India slowed the spread of COVID-19 epidemic dynamics Content: Background The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects on epidemic dynamics are yet to be understood. Methods Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Findings Daily case rates ranged from 0.03 to 30.05/10 million people across 4 discrete periods in India. From May 4-17, 2020, the National Capital Territory (NCT) of Delhi had the highest case rate (222/10 million people/day), whereas Kerala had the lowest (2.18/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) for India; it ranged from 1.38 to 2.78, decreasing over time. Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value. Interpretation The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India. Funding Non-funded.", "qid": 10, "docid": "nney9kuq", "rank": 74, "score": 11.07289981842041}, {"content": "Title: Public perceptions and experiences of social distancing and social isolation during the COVID-19 pandemic: A UK-based focus group study Content: OBJECTIVE: Explore the perceptions and experiences of the UK public of social distancing and social isolation measures related to the COVID-19 pandemic. DESIGN: Qualitative study comprising five focus groups carried out online during the early stages of the UK's social distancing and isolation measures (5-12 days post lockdown). SETTING: Online video-conferencing PARTICIPANTS: 27 participants, all UK residents aged 18 years and older, representing a range of gender, ethnic, age and occupational backgrounds. RESULTS: The social distancing and isolation associated with COVID-19 policy has had having substantial negative impacts on the mental health and wellbeing of the UK public within a short time of policy implementation. It has disproportionately negatively affected those in low-paid or precarious employment. Practical social and economic losses - the loss of (in-person) social interaction, loss of income and loss of structure and routine - led to psychological and emotional 'losses' - the loss of motivation, loss of meaning, and loss of self-worth. Participants reported high adherence to distancing and isolation guidelines but reported seeing or hearing of non-adherence in others. A central concern for participants was the uncertainty duration of the measures, and their ability to cope longer-term. Some participants felt they would have lingering concerns over social contact while others were eager to return to high levels of social activity. CONCLUSIONS: A rapid response is necessary in terms of public health programming to mitigate the mental health impacts of COVID-19 social distancing and isolation. Initial high levels of support for, and adherence to, social distancing and isolation is likely to wane over time, particularly where end dates are uncertain. Social distancing and isolation 'exit strategies' must account for the fact that, although some individuals will voluntarily or habitually continue to socially distance, others will seek high levels of social engagement as soon as possible.", "qid": 10, "docid": "kweh1doo", "rank": 75, "score": 11.053600311279297}, {"content": "Title: Quantifying what could have been \u2013 the impact of the Australian and New Zealand governments\u2019 response to COVID-19 Content: The Australian and New Zealand governments both initiated strict social distancing measures in response to the COVID-19 pandemic in late March. It remains difficult to quantify the impact this had in reducing the spread of the virus. Bayesian structural time series model provide a model to quantify the scenario in which these government-level interventions were not placed. Our models predict these strict social distancing measures caused a 79% and 61% reduction in the daily cases of COVID-19 across Australia and New Zealand respectively. This provides both evidence and impetus for governments considering similar measures in response to COVID-19 and other pandemics.", "qid": 10, "docid": "hzpbujye", "rank": 76, "score": 10.994600296020508}, {"content": "Title: Lack of sufficient public space can limit the effectiveness of COVID-19's social distancing measures Content: One of the primary strategies of slowing down the COVID-19 pandemic has been the establishment of social distancing rules that recommend keeping a buffer distance between individuals, and this has proven effective in helping in reducing the basic reproduction number [R 0] . However, social distancing rules have put the use of public spaces in densely populated places under strain, and this is especially important as some of the most virulent outbreaks of the COVID-19 pandemic have been in compact cities. It is therefore fundamental to take into account each neighbourhood's morphological characteristics and the potential population densities each street, square or park can accommodate under such new regulations in order to effectively enforce social distancing rules. Otherwise, certain areas may be rapidly overwhelmed by crowds with citizens unable to maintain the minimum safe distance between individuals. In this paper, we develop a method to identify the potential public space accessibility if social distancing rules are followed and we apply it to three global and highly affected by COVID-19 cities. Our research finds that, at micro level there are important inequalities between neighbourhoods, so people will struggle to comply with social distancing rules and consequently it will make controlling infection rates more difficult.", "qid": 10, "docid": "qh96bfi6", "rank": 77, "score": 10.97819995880127}, {"content": "Title: Risk Management of COVID-19 by Universities in China Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13\u201323, 2020 Content: The rapid spread of new coronaviruses throughout China and the world in 2019&ndash;2020 has had a great impact on China&rsquo;s economic and social development As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation However, they also face the problems of alumni&rsquo;s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic&rsquo;s epicenter Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang;however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang Our 10-day forecasts across the three models predict an additional 65&ndash;81 cases (upper bounds: 169&ndash;507) in Guangdong and an additional 44&ndash;354 (upper bounds: 141&ndash;875) cases in Zhejiang by February 23, 2020 In the best-case scenario, current data suggest that transmission in both provinces is slowing down", "qid": 10, "docid": "4xpkzx0h", "rank": 78, "score": 10.968899726867676}, {"content": "Title: Public activities preceding the onset of acute respiratory infection syndromes in adults in England - implications for the use of social distancing to control pandemic respiratory infections. Content: Background: Social distancing measures may reduce the spread of emerging respiratory infections however, there is little empirical data on how exposure to crowded places affects risk of acute respiratory infection. Methods: We used a case-crossover design nested in a community cohort to compare self-reported measures of activities during the week before infection onset and baseline periods. The design eliminates the effect of non-time-varying confounders. Time-varying confounders were addressed by exclusion of illnesses around the Christmas period and seasonal adjustment. Results: 626 participants had paired data from the week before 1005 illnesses and the week before baseline. Each additional day of undertaking the following activities in the prior week was associated with illness onset: Spending more than five minutes in a room with someone (other than a household member) who has a cold (Seasonally adjusted OR 1\u00b715, p=0\u00b7003); use of underground trains (1\u00b731, p=0\u00b7036); use of supermarkets (1\u00b732, p<0\u00b7001); attending a theatre, cinema or concert (1\u00b726, p=0\u00b7032); eating out at a caf\u00e9, restaurant or canteen (1\u00b725, p=0\u00b7003); and attending parties (1\u00b747, p<0\u00b7001). Undertaking the following activities at least once in the previous week was associated with illness onset: using a bus, (aOR 1.48, p=0.049), shopping at small shops (1.9, p<0.002) attending a place of worship (1.81, p=0.005). Conclusions: Exposure to potentially crowded places, public transport and to individuals with a cold increases risk of acquiring circulating acute respiratory infections. This suggests social distancing measures can have an important impact on slowing transmission of emerging respiratory infections.", "qid": 10, "docid": "vs1zu7z5", "rank": 79, "score": 10.963800430297852}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: Background: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). Methods: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire documents the age and location of contacts and as well as a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday 24th March, one day after a \u201clockdown\u201d was implemented across the UK. We compared measured contact patterns during the lockdown to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. Findings: We found a 73% reduction in the average daily number of contacts observed per participant (from 10.2 to 2.9). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37 - 0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22 - 0.53) for physical contacts only. Interpretation: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "8do4tojk", "rank": 80, "score": 10.954000473022461}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a \"lockdown\" was implemented across the UK. We compared measured contact patterns during the \"lockdown\" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37-0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22-0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "fac4ic30", "rank": 81, "score": 10.953999519348145}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R(0), the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a \u201clockdown\u201d was implemented across the UK. We compared measured contact patterns during the \u201clockdown\u201d to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R(0) from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37\u20130.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22\u20130.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "rqotfwm3", "rank": 82, "score": 10.953998565673828}, {"content": "Title: Estimating the impact of COVID-19 control measures using a Bayesian model of physical distancing Content: Extensive physical distancing measures are currently the primary intervention against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing measures, with the timing of these measures informed by survey data on attitudes to distancing and COVID-19.We fit our model to reported COVID-19 cases in British Columbia, Canada, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimate the impact that physical distancing (also known as social distancing)has had on the contact rate and examine the projected impact of relaxing distancing measures. We find that distancing has had a strong impact, consistent with declines in reported cases and in hospitalization and intensive care unit numbers. We estimate that approximately 0.78 (0.66-0.89 90% CI) of contacts have been removed for individuals in British Columbia practising physical distancing and that this fraction is above the threshold of 0.45 at which prevalence is expected to grow. However, relaxing distancing measures beyond this threshold re-starts rapid exponential growth. Because the extent of underestimation is unknown, the data are consistent with a wide range in the prevalence of COVID-19 in the population; changes to testing criteria over time introduce additional uncertainty. Our projections indicate that intermittent distancing measures - if sufficiently strong and robustly followed - could control COVID-19 transmission, but that if distancing measures are relaxed too much, the epidemic curve would grow to high prevalence.", "qid": 10, "docid": "77ebl84a", "rank": 83, "score": 10.946000099182129}, {"content": "Title: Quantifying what could have been - The impact of the Australian and New Zealand governments' response to COVID-19 Content: BACKGROUND: The Australian and New Zealand governments both initiated strict social distancing measures in response to the COVID-19 pandemic in late March. It remains difficult to quantify the impact this had in reducing the spread of the virus. METHODS: Bayesian structural time series model provide a model to quantify the scenario in which these government-level interventions were not placed. Our models predict these strict social distancing measures caused a 79% and 61% reduction in the daily cases of COVID-19 across Australia and New Zealand respectively. CONCLUSION: This provides both evidence and impetus for governments considering similar measures in response to COVID-19 and other pandemics.", "qid": 10, "docid": "xjr582j3", "rank": 84, "score": 10.945099830627441}, {"content": "Title: Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate Content: State and local governments imposed social distancing measures in March and April 2020 to contain the spread of the novel coronavirus disease (COVID-19). These measures included bans on large social gatherings; school closures; closures of entertainment venues, gyms, bars, and restaurant dining areas; and shelter-in-place orders. We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020, and April 27, 2020. An event study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate of confirmed COVID-19 cases by 5.4 percentage points after one to five days, 6.8 percentage points after six to ten days, 8.2 percentage points after eleven to fifteen days, and 9.1 percentage points after sixteen to twenty days. Holding the amount of voluntary social distancing constant, these results imply that there would have been ten times greater spread of COVID-19 by April 27 without shelter-in-place orders (ten million cases) and more than thirty-five times greater spread without any of the four measures (thirty-five million cases). Our article illustrates the potential danger of exponential spread in the absence of interventions, providing information relevant to strategies for restarting economic activity.", "qid": 10, "docid": "h62xj47p", "rank": 85, "score": 10.936300277709961}, {"content": "Title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak Content: The novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that \u201con-off\u201d policies alternating between strict social distancing and relaxing such restrictions can be effective at \u201cflattening\u201d the curve while likely minimizing social and economic cost.", "qid": 10, "docid": "o8uk6if2", "rank": 86, "score": 10.932000160217285}, {"content": "Title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak Content: The novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that \"on-off\" policies alternating between strict social distancing and relaxing such restrictions can be effective at \"flattening\" the curve while likely minimizing social and economic cost.", "qid": 10, "docid": "wtk27dhx", "rank": 87, "score": 10.931999206542969}, {"content": "Title: Early transmission dynamics of COVID-19 in Chile: From sub-exponential ascending growth dynamics to a stationary disease wave, March-April, 2020 Content: The COVID-19 pandemic reached Latin America in February 2020, with the first case in Chile identified on March 3rd, 2020. Since then Chile has accumulated a total of 14365 cases as of April 28th, 2020. We estimate the reproduction number during the early transmission phase in Chile and study the effectiveness of control interventions by conducting short-term forecasts based on early transmission dynamics of COVID-19. The incidence curve displays sub-exponential growth dynamics with the scaling of growth parameter, p, estimated at 0.8 (95% CI: 0.7, 0.8) and the reproduction number estimated at 1.6 (95% CI: 1.5, 1.6). The sub-epidemic model indicates a stationary wave of stable epidemic size. Our current findings point to sustained transmission of SARS-CoV-2 in Chile. While the social distancing interventions have slowed the virus spread, the number of new COVID-19 cases continue to accrue, underscoring the need for persistent social distancing efforts to control the epidemic.", "qid": 10, "docid": "4ii345m6", "rank": 88, "score": 10.92240047454834}, {"content": "Title: Intersecting Pandemics: Impact of SARS-CoV-2 (COVID-19) Protective Behaviors on People Living with HIV, Atlanta, Georgia. Content: BACKGROUND COVID-19 and its social responses threaten the health of people living with HIV. We conducted a rapid-response interview to assess COVID-19 protective behaviors of people living with HIV and the impact of their responses on HIV related healthcare. METHOD Men and women living with HIV (N = 162) ages 20 to 37 participating in a longitudinal study of HIV treatment and care completed routine study measures and an assessment of COVID-19-related experiences. RESULTS At baseline, a majority of participants demonstrated HIV viremia, markers indicative of renal disorders, and biologically confirmed substance use. At follow-up, in the first month of responding to COVID-19, engaging in more social distancing behaviors was related to difficulty accessing food and medications, and increased cancelation of healthcare appointments, both by self and providers. We observed ART adherence had improved during the initial month of COVID-19 response. CONCLUSIONS Factors that may pose added risk for COVID-19 severity were prevalent among people living with HIV and those with greater risk factors did not practice more COVID-19 protective behaviors. Social distancing and other practices intended to mitigate the spread of COVID-19 interfered with HIV care, and impeded access to food and medications, although an immediate adverse impact on medication adherence was not evident. These results suggest social responses to COVID-19 adversely impacted the healthcare of people living with HIV, supporting continued monitoring to determine the long-term effects of co-occurring HIV and COVID-19 pandemics.", "qid": 10, "docid": "1buh1wm0", "rank": 89, "score": 10.919699668884277}, {"content": "Title: Intersecting Pandemics: Impact of SARS-CoV-2 (COVID-19) Protective Behaviors on People Living with HIV, Atlanta, Georgia Content: BACKGROUND: COVID-19 and its social responses threaten the health of people living with HIV. We conducted a rapid-response interview to assess COVID-19 protective behaviors of people living with HIV and the impact of their responses on HIV related healthcare. METHOD: Men and women living with HIV (N = 162) ages 20 to 37 participating in a longitudinal study of HIV treatment and care completed routine study measures and an assessment of COVID-19-related experiences. RESULTS: At baseline, a majority of participants demonstrated HIV viremia, markers indicative of renal disorders, and biologically confirmed substance use. At follow-up, in the first month of responding to COVID-19, engaging in more social distancing behaviors was related to difficulty accessing food and medications, and increased cancelation of healthcare appointments, both by self and providers. We observed ART adherence had improved during the initial month of COVID-19 response. CONCLUSIONS: Factors that may pose added risk for COVID-19 severity were prevalent among people living with HIV and those with greater risk factors did not practice more COVID-19 protective behaviors. Social distancing and other practices intended to mitigate the spread of COVID-19 interfered with HIV care, and impeded access to food and medications, although an immediate adverse impact on medication adherence was not evident. These results suggest social responses to COVID-19 adversely impacted the healthcare of people living with HIV, supporting continued monitoring to determine the long-term effects of co-occurring HIV and COVID-19 pandemics.", "qid": 10, "docid": "dfwia886", "rank": 90, "score": 10.919698715209961}, {"content": "Title: Observed mobility behavior data reveal social distancing inertia Content: The research team has utilized an integrated dataset, consisting of anonymized location data, COVID-19 case data, and census population information, to study the impact of COVID-19 on human mobility. The study revealed that statistics related to social distancing, namely trip rate, miles traveled per person, and percentage of population staying at home have all showed an unexpected trend, which we named social distancing inertia. The trends showed that as soon as COVID-19 cases were observed, the statistics started improving, regardless of government actions. This suggests that a portion of population who could and were willing to practice social distancing voluntarily and naturally reacted to the emergence of COVID-19 cases. However, after about two weeks, the statistics saturated and stopped improving, despite the continuous rise in COVID-19 cases. The study suggests that there is a natural behavior inertia toward social distancing, which puts a limit on the extent of improvement in the social-distancing-related statistics. The national data showed that the inertia phenomenon is universal, happening in all the U.S. states and for all the studied statistics. The U.S. states showed a synchronized trend, regardless of the timeline of their statewide COVID-19 case spreads or government orders.", "qid": 10, "docid": "hb1r2aw7", "rank": 91, "score": 10.91409969329834}, {"content": "Title: Orthopaedic Surgical Selection and Inpatient Paradigms During the Coronavirus (COVID-19) Pandemic Content: The novel coronavirus pandemic, also known as SARS-CoV-2, has placed an immense strain on healthcare systems across the entire world. Consequently, multiple federal and state governments have placed restrictions on hospitals such as limiting \u201celective surgery\u201d and recommending social or physical distancing. We review the literature on several areas that have been affected including surgical selection, inpatient care, and physician well-being. These areas affecting inpatient paradigms include surgical priority, physical or social distancing, file sharing for online clinical communications, and physician wellness. During this crisis, it is important that orthopaedic departments place an emphasis on personnel safety and slowing the spread of the virus so that the department can still maintain vital functions. Physical distancing and emerging technologies such as inpatient telemedicine and online file sharing applications can enable orthopaedic programs to still function while attempting to protect medical staff and patients from the novel coronavirus spread. This literature review sought to provide evidence-based guidance to orthopaedic departments during an unprecedented time. Orthopaedic surgeons should follow the Centers for Disease Control and Prevention guidelines, wear PPE when appropriate, have teams created using physical distancing, understand the department's policy on elective surgery, and engage in routines which enhance physician wellness.", "qid": 10, "docid": "btgp7dkj", "rank": 92, "score": 10.898099899291992}, {"content": "Title: Spring in London with Covid-19: a personal view Content: This is a personal view from London as the Covid-19 pandemic continues to spread here and the situation changes from day to day. As such it can only be a snapshot caught in time; it is not a diary of events. The Coronavirus Act 2020 gives Government enormous powers and was passed by Parliament in one day of debate immediately before it closed early for the Easter break. In March, the government imposed a \"lockdown: the closure of all\" but \"essential\" businesses and people other than essential workers must work from home but are allowed out for exercise and food shopping but must maintain 2 m apart, the \"social distancing rule\". The aim is to suppress the spread of the virus, reduce the death toll and \"protect the National Health Service (NHS)\" which needed time to empty wards and expand its intensive care unit (ICU) capability to deal with an expected influx of thousands of very sick patients. I discuss whether this strategy is working, how and why it has rapidly been altered to respond to criticism. Why was the Government so slow to seek the help of private laboratories to assist with testing? Why was the personal protective equipment (PPE) guidance altered only after criticism? I look at the impact of the lockdown on the UK economy, the changes to practice of medicine and speeding of scientific research. Cooperating with the lockdown has its price; is it harming the health and mental health of children, people living in households with potentially abusive partners or parents and those who are disabled or financially desperate? Is the cure worse than the disease? The Economy is being devastated by the lockdown and each day of lockdown it is worse. Is litigation being seeded even now by the pandemic? Notwithstanding unprecedented Government financial help many businesses are on the edge of collapse, people will lose their jobs and pensioners income. The winners include pharmacies, supermarkets, online food retailers, Amazon, online apps, providers of video games, services, streaming and scientific research laboratories, manufacturers of testing kits, ventilators, hand sanitisers, coffins, undertakers, etc. The British public is cooperating with lockdown but are we less productive at home? Parents with babies and children often child minders, school, grandparents or paid help which is not now available. Will current reliance on video-conferencing and video calls permanently change the way we work and will we need smaller city offices? Will we travel less? Will medical and legal practice and civil and criminal trials be generally carried out remotely? Will social distancing with self-isolation and job losses and business failures fuel depression? Is Covid-19 comparable to past epidemics like the Plague and Spanish flu?", "qid": 10, "docid": "87i01hsi", "rank": 93, "score": 10.885299682617188}, {"content": "Title: Spring in London with Covid-19: a personal view. Content: This is a personal view from London as the Covid-19 pandemic continues to spread here and the situation changes from day to day. As such it can only be a snapshot caught in time; it is not a diary of events. The Coronavirus Act 2020 gives Government enormous powers and was passed by Parliament in one day of debate immediately before it closed early for the Easter break. In March, the government imposed a \"lockdown: the closure of all\" but \"essential\" businesses and people other than essential workers must work from home but are allowed out for exercise and food shopping but must maintain 2 m apart, the \"social distancing rule\". The aim is to suppress the spread of the virus, reduce the death toll and \"protect the National Health Service (NHS)\" which needed time to empty wards and expand its intensive care unit (ICU) capability to deal with an expected influx of thousands of very sick patients. I discuss whether this strategy is working, how and why it has rapidly been altered to respond to criticism. Why was the Government so slow to seek the help of private laboratories to assist with testing? Why was the personal protective equipment (PPE) guidance altered only after criticism? I look at the impact of the lockdown on the UK economy, the changes to practice of medicine and speeding of scientific research. Cooperating with the lockdown has its price; is it harming the health and mental health of children, people living in households with potentially abusive partners or parents and those who are disabled or financially desperate? Is the cure worse than the disease? The Economy is being devastated by the lockdown and each day of lockdown it is worse. Is litigation being seeded even now by the pandemic? Notwithstanding unprecedented Government financial help many businesses are on the edge of collapse, people will lose their jobs and pensioners income. The winners include pharmacies, supermarkets, online food retailers, Amazon, online apps, providers of video games, services, streaming and scientific research laboratories, manufacturers of testing kits, ventilators, hand sanitisers, coffins, undertakers, etc. The British public is cooperating with lockdown but are we less productive at home? Parents with babies and children often child minders, school, grandparents or paid help which is not now available. Will current reliance on video-conferencing and video calls permanently change the way we work and will we need smaller city offices? Will we travel less? Will medical and legal practice and civil and criminal trials be generally carried out remotely? Will social distancing with self-isolation and job losses and business failures fuel depression? Is Covid-19 comparable to past epidemics like the Plague and Spanish flu?", "qid": 10, "docid": "hbalyfy3", "rank": 94, "score": 10.885298728942871}, {"content": "Title: Differences in power-law growth over time and indicators of COVID-19 pandemic progression worldwide Content: An automated statistical and error analysis of 45 countries or regions with more than 1000 cases of COVID-19 as of March 28, 2020, has been performed. This study reveals differences in the rate of disease spreading rate over time in different countries. This survey observes that most countries undergo a beginning exponential growth phase, which transitions into a power-law phase, as recently suggested by Ziff and Ziff. Tracking indicators of growth, such as the power-law exponent, are a good indication of the relative danger different countries are in and show when social measures are effective towards slowing the spread. The data compiled here are usefully synthesizing a global picture, identifying country to country variation in spreading, and identifying countries most at risk. This analysis may factor into how best to track the effectiveness of social distancing policies and quarantines in real-time as data is updated each day.", "qid": 10, "docid": "rc88vn6e", "rank": 95, "score": 10.880399703979492}, {"content": "Title: Containing the Spread of Coronavirus Disease 2019 (COVID-19): Meteorological Factors and Control Strategies Content: The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We found that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten onset-to-isolation time is markedly reduced and the importance of contact tracing and quarantine and social distancing increases. The analytic results also highlight the importance of early intervention to contain the spread of COVID-19.", "qid": 10, "docid": "vxy41zov", "rank": 96, "score": 10.848199844360352}, {"content": "Title: Network model and analysis of the spread of Covid-19 with social distancing Content: The first mitigation response to the Covid-19 pandemic was to limit person-to-person interaction as much as possible. This was implemented by the temporary closing of many workplaces and people were required to follow social distancing. Networks are a great way to represent interactions among people and the temporary severing of these interactions. Here, we present a network model of human-human interactions that could be mediators of disease spread. The nodes of this network are individuals and different types of edges denote family cliques, workplace interactions, interactions arising from essential needs, and social interactions. Each individual can be in one of four states: susceptible, infected, immune, and dead. The network and the disease parameters are informed by the existing literature on Covid-19. Using this model, we simulate the spread of an infectious disease in the presence of various mitigation scenarios. For example, lockdown is implemented by deleting edges that denote non-essential interactions. We validate the simulation results with the real data by matching the basic and effective reproduction numbers during different phases of the spread. We also simulate different possibilities of the slow lifting of the lockdown by varying the transmission rate as facilities are slowly opened but people follow prevention measures like wearing masks etc. We make predictions on the probability and intensity of a second wave of infection in each of these scenarios.", "qid": 10, "docid": "yat5g2i9", "rank": 97, "score": 10.837499618530273}, {"content": "Title: Containing the spread of coronavirus disease 2019 (COVID-19): Meteorological factors and control strategies Content: Abstract The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We find that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten treatment time is markedly reduced and the importance of contact quarantine and social distancing increases.", "qid": 10, "docid": "6imghzg1", "rank": 98, "score": 10.826600074768066}, {"content": "Title: Understanding the impact of the COVID-19 pandemic on well-being and virtual care for people living with dementia and care partners living in the community Content: The COVID-19 pandemic has necessitated public health measures that have impacted the provision of care for people living with dementia and their families. Additionally, the isolation that results from social distancing may be harming well-being for families, as formal and informal supports become less accessible. For those with living with dementia and experiencing agitation, social distancing may be even harder to maintain, or social distancing could potentially aggravate dementia-related neuropsychiatric symptoms. To understand the lived experience of social and physical distancing during the COVID-19 pandemic in Canada we remotely interviewed 21 participants who normally attend a dementia specialty clinic in Calgary, Alberta, during a period where essential businesses were closed and healthcare had abruptly transitioned to telemedicine. The impacts of the public health measures in response to the pandemic emerged in three main categories of experience: 1) personal; 2) health services; and 3) health status (of both person living with dementia and care partner). This in-depth understanding of the needs and experiences of the pandemic for people living with dementia suggests that innovative means are urgently needed to facilitate provision of remote medicine and also social interaction and integration.", "qid": 10, "docid": "pzmo4hja", "rank": 99, "score": 10.802000045776367}, {"content": "Title: Centralized and decentralized isolation strategies and their impact on the COVID-19 pandemic dynamics Content: The infectious diseases are spreading due to human interactions enabled by various social networks. Therefore, when a new pathogen such as SARS-CoV-2 causes an outbreak, the non-pharmaceutical isolation strategies (e.g., social distancing) are the only possible response to disrupt its spreading. To this end, we introduce the new epidemic model (SICARS) and compare the centralized (C), decentralized (D), and combined (C+D) social distancing strategies, and analyze their efficiency to control the dynamics of COVID-19 on heterogeneous complex networks. Our analysis shows that the centralized social distancing is necessary to minimize the pandemic spreading. The decentralized strategy is insufficient when used alone, but offers the best results when combined with the centralized one. Indeed, the (C+D) is the most efficient isolation strategy at mitigating the network superspreaders and reducing the highest node degrees to less than 10% of their initial values. Our results also indicate that stronger social distancing, e.g., cutting 75% of social ties, can reduce the outbreak by 75% for the C isolation, by 33% for the D isolation, and by 87% for the (C+D) isolation strategy. Finally, we study the impact of proactive versus reactive isolation strategies, as well as their delayed enforcement. We find that the reactive response to the pandemic is less efficient, and delaying the adoption of isolation measures by over one month (since the outbreak onset in a region) can have alarming effects; thus, our study contributes to an understanding of the COVID-19 pandemic both in space and time. We believe our investigations have a high social relevance as they provide insights into understanding how different degrees of social distancing can reduce the peak infection ratio substantially; this can make the COVID-19 pandemic easier to understand and control over an extended period of time.", "qid": 10, "docid": "ts3ra09u", "rank": 100, "score": 10.784700393676758}]}
{"query": "what are the guidelines for triaging patients infected with coronavirus?", "hits": [{"content": "Title: Israel Ad Hoc COVID\u201019 Committee: Guidelines for Care of Older Persons During a Pandemic Content: Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID\u201019). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long\u2010term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a \u201csoft utilitarian\u201d approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, \u201cbiological age\u201d would enter into the triage considerations, but only in the case of distinguishing between people with equal non\u2013age\u2010related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD\u201019 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation.", "qid": 11, "docid": "lb099dyt", "rank": 1, "score": 9.555500030517578}, {"content": "Title: Israel Ad Hoc COVID-19 Committee: Guidelines for Care of Older Persons During a Pandemic Content: Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID-19). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long-term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a \"soft utilitarian\" approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, \"biological age\" would enter into the triage considerations, but only in the case of distinguishing between people with equal non-age-related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD-19 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation. J Am Geriatr Soc 68:1370-1375, 2020.", "qid": 11, "docid": "ce4p827u", "rank": 2, "score": 9.401800155639648}, {"content": "Title: Ethicists, doctors and triage decisions: who should decide? And on what basis? Content: We report here an emerging dispute in Italy concerning triage criteria for critically ill covid-19 patients, and how best to support doctors having to make difficult decisions in a context of insufficient life saving resources. The dispute we present is particularly significant as it juxtaposes two opposite views of who should make triage decisions, and how doctors should best be supported. There are both empirical and normative questions at stake here. The empirical questions pertain to the available level of evidence that healthcare professionals would rather not be left alone with their 'clinical judgments' to make triage decisions, and to the accounts of distributive justice that doctors and healthcare professionals rely on, when making triage decisions. The normative questions pertain to how this empirical evidence should inform guidelines on how prioritisation decisions are made in a context of emergency, and who gets to have the authority to do so. This debate goes beyond the discussion of the care of critically ill patients with COVID-19 and has broader implications beyond the national context for the discussion of how to relieve moral distress in contexts of imbalances between healthcare resources and clinical needs of a population.", "qid": 11, "docid": "t7iyt5d4", "rank": 3, "score": 8.796799659729004}, {"content": "Title: Rapid De-Escalation and Triaging Patients in Community-Based Palliative Care Content: CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? MEASURES: The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. CONCLUSIONS/LESSONS LEARNED: We recommend active triaging, communication, and frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.", "qid": 11, "docid": "eazqdlds", "rank": 4, "score": 8.572999954223633}, {"content": "Title: Triage Content: This review provides an overview of triaging critically ill or injured patients during mass casualty incidents due to events such as disasters, pandemics, or terrorist incidents. Questions clinicians commonly have, including \u201cwhat is triage?,\u201d \u201cwhen to triage?,\u201d \u201cwhat are the types of disaster triage?,\u201d \u201chow to triage?,\u201d \u201cwhat are the ethics of triage?,\u201d \u201chow to govern triage?,\u201d and \u201cwhat research is required on triage?,\u201d are addressed.", "qid": 11, "docid": "gwle80we", "rank": 5, "score": 8.542699813842773}, {"content": "Title: Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study Content: Background: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods: We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (&#8804;9\u00e2\u0080\u00a25 109/L) or lymphopenia (<1\u00e2\u0080\u00a21 109/L). Findings: Normal or decreased number of leukocytes (&#8804;9\u00e2\u0080\u00a25 109/L), lymphopenia (<1\u00e2\u0080\u00a21 109/L), eosinopenia (<0\u00e2\u0080\u00a202 109/L), and elevated hs-CRP (&#8805;4 mg/L) were presented in 95\u00e2\u0080\u00a20%, 52\u00e2\u0080\u00a22%, 74\u00e2\u0080\u00a27% and 86\u00e2\u0080\u00a27% of COVID-19 patients, much higher than 87\u00e2\u0080\u00a22%, 28\u00e2\u0080\u00a28%, 31\u00e2\u0080\u00a23% and 45\u00e2\u0080\u00a22% of the controls, respectively. The eosinopenia produced a sensitivity of 74\u00e2\u0080\u00a27% and specificity of 68\u00e2\u0080\u00a27% for separating the two groups with the area under the curve (AUC) of 0\u00e2\u0080\u00a2717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67\u00e2\u0080\u00a29% and specificity of 78\u00e2\u0080\u00a22% (AUC=0\u00e2\u0080\u00a2730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation: The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding: This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP).", "qid": 11, "docid": "37dauvku", "rank": 6, "score": 8.527199745178223}, {"content": "Title: Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study Content: Abstract Background Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (\u22649\u20225 109/L) or lymphopenia (<1\u20221 109/L). Findings Normal or decreased number of leukocytes (\u22649\u20225 109/L), lymphopenia (<1\u20221 109/L), eosinopenia (<0\u202202 109/L), and elevated hs-CRP (\u22654 mg/L) were presented in 95\u20220%, 52\u20222%, 74\u20227% and 86\u20227% of COVID-19 patients, much higher than 87\u20222%, 28\u20228%, 31\u20223% and 45\u20222% of the controls, respectively. The eosinopenia produced a sensitivity of 74\u20227% and specificity of 68\u20227% for separating the two groups with the area under the curve (AUC) of 0\u2022717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67\u20229% and specificity of 78\u20222% (AUC=0\u2022730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP).", "qid": 11, "docid": "nf2vd6o1", "rank": 7, "score": 8.527198791503906}, {"content": "Title: Management of valvular and structural heart diseases during the coronavirus disease 2019 pandemic: an expert opinion of the Working Group on Valvular Heart Diseases, the Working Group on Cardiac Surgery, and the Association of Cardiovascular Interventions of the Polish Cardiac Society Content: The ongoing pandemic of coronavirus disease 2019 (COVID\u00ad19), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u00adCoV\u00ad2), represents a major challenge for healthcare. The involvement of cardiovascular system in COVID\u00ad19 has been proven and increased healthcare system resources are redirected towards handling infected patients, which induces major changes in access to services and prioritization in the management of patients with chronic cardiovascular disease unrelated to COVID\u00ad19. In this expert opinion, conceived by the task force involving the Working Groups on Valvular Heart Diseases and Cardiac Surgery as well as the Association of Cardiovascular Intervention of the Polish Cardiac Society, modification of diagnostic pathways, principles of healthcare personnel protection, and treatment guidelines regarding triage and prioritization are suggested. Heart Teams responsible for the treatment of valvular heart disease should continue their work using telemedicine and digital technology. Diagnostic tests must be simplified or deferred to minimize the number of potentially dangerous aerosol\u00adgenerating procedures, such as transesophageal echocardiography or exercise imaging. The treatment of aortic stenosis and mitral regurgitation has to be offered particularly due to urgent indications and in patients with advanced disease and poor prognosis. Expert risk stratification is essential for triage and setting the priority lists. In each case, an appropriate level of personal protection must be ensured for the healthcare personnel to prevent spreading infection and preserve specialized manpower, who will supply the continuing need for handling serious chronic cardiovascular disease. Importantly, as soon as the local epidemic situation improves, efforts must be made to restore standard opportunities for elective treatment of valvular heart disease and occluder\u00adbased therapies according to existing guidelines, thus rebuilding the state \u00adof \u00adthe \u00adart cardiovascular services.", "qid": 11, "docid": "6coookt6", "rank": 8, "score": 8.336299896240234}, {"content": "Title: The role of triage in the prevention and control of COVID-19 Content: OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),(4) issued by the National Health Commission of the People\u2019s Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.", "qid": 11, "docid": "4jag7lzb", "rank": 9, "score": 8.292699813842773}, {"content": "Title: The role of triage in the prevention and control of COVID-19 Content: OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),4 issued by the National Health Commission of the People's Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.", "qid": 11, "docid": "jv3xx09f", "rank": 10, "score": 8.292698860168457}, {"content": "Title: Urologic oncology surgery during COVID-19: a rapid review of current triage guidance documents Content: The Coronavirus Disease 2019 pandemic placed urologic surgeons, and especially urologic oncologists, in an unprecedented situation. Providers and healthcare systems were forced to rapidly create triage schemas in order to preserve resources and reduce potential viral transmission while continuing to provide care for patients. We reviewed United States and international triage proposals from professional societies, peer-reviewed publications, and publicly available institutional guidelines to identify common themes and critical differences. To date, there are varying levels of agreement on the optimal triaging of urologic oncology cases. As the need to preserve resources and prevent viral transmission grows, prioritizing only high priority surgical cases is paramount. A similar approach to prioritization will also be needed as nonemergent cases are allowed to proceed in the coming weeks. While these decisions will often be made on a case-by-case basis, more nuanced surgeon-driven consensus guidelines are needed for the near future.", "qid": 11, "docid": "f7i85959", "rank": 11, "score": 8.159700393676758}, {"content": "Title: Covid-19: A view from New York Content: I live in New York City, identified as the epicenter of the Covid-19 pandemic. My view differs from that of many of the millions living in this large metropolitan area who are poor. I am not rich, but I am privileged: I have a retirement income for which I have saved all my working life and I have no debts. I am isolated in my apartment having food delivered. But what if I require hospitalization, from Covid-19 or another medical condition? New York State has guidelines for allocation of scarce ventilators in times of scarcity. The guidelines reject advanced age as a criterion for triage because it discriminates against the elderly. Other proposals contend that priority should be given to those who have not yet ;lived a full life. Allocation guidelines set a priority on saving the most lives, but hard choices remain within that broadly defined goal. Key words: Covid-19 pandemic, New York epicenter, resource allocation, age-based selection, shortage of ventilators, triage committee.", "qid": 11, "docid": "nbcymm5e", "rank": 12, "score": 8.116499900817871}, {"content": "Title: Covid-19: A view from New York. Content: I live in New York City, identified as the epicenter of the Covid-19 pandemic. My view differs from that of many of the millions living in this large metropolitan area who are poor. I am not rich, but I am privileged: I have a retirement income for which I have saved all my working life and I have no debts. I am isolated in my apartment having food delivered. But what if I require hospitalization, from Covid-19 or another medical condition? New York State has guidelines for allocation of scarce ventilators in times of scarcity. The guidelines reject advanced age as a criterion for triage because it discriminates against the elderly. Other proposals contend that priority should be given to those who have not yet ;lived a full life. Allocation guidelines set a priority on saving the most lives, but hard choices remain within that broadly defined goal. Key words: Covid-19 pandemic, New York epicenter, resource allocation, age-based selection, shortage of ventilators, triage committee.", "qid": 11, "docid": "zw6zvni4", "rank": 13, "score": 8.116498947143555}, {"content": "Title: Analysis and suggestions for the preview and triage screening of children with suspected COVID-19 outside the epidemic area of Hubei Province Content: Background: Since December 2019, a number of patients infected with COVID-19 (SARS-CoV-2) have been identified in Wuhan, Hubei, China. As the epidemic has spread, similar cases have also been found in other parts of mainland China and abroad. The main reason for this spread is the highly contagious nature of the virus and the fact that children can also become infected during its incubation period. This has made the virus a substantial challenge for the outpatient triage staff of children's hospitals outside the epidemic area of the Hubei Province. It is very important for the preview and triage personnel to accurately grasp the epidemiology of the virus and identify children's symptoms in the fever clinic. Methods: We performed an analysis of our early preview and triage of suspected COVID-19 in 36 children presenting at fever clinics. Two specialists either excluded suspected cases or referred cases to the isolation ward for new nucleic acid testing. Results: All 14 children who were transferred to the isolation ward had a fever, and 71.43% of them had a cough. Their nucleic acid testing results were negative. The suspected cases and excluded suspected cases had similar epidemiology history as well as complete blood count results. With reference to the diagnostic criteria in existing pediatric guidelines, we have further improved the triage screening questionnaire for children with fever in our hospital. Conclusions: According to the situation in our city and hospital, an evaluation questionnaire that is suitable for use with children in our hospital has been formulated to achieve the goals of early detection, isolation, diagnosis, and treatment. We provided an important basis for the next step in developing accurate preview and triage screening standards and appropriate guidelines for pediatric patients.", "qid": 11, "docid": "macqp9k1", "rank": 14, "score": 8.112700462341309}, {"content": "Title: Principles for Managing Patients with Spinal Ailments in the Coronavirus Disease 2019 Era: What Do We Know So Far? An Evidence-Based, Narrative Review Content: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected all specialty practices in medicine, including the field of spinal surgery. Spinal surgery is unique in that the procedures include not only fully elective and fully emergent interventions, but also involve a separate group of semi-emergent surgeries, where delayed intervention may lead to permanent neurological deficits. Here, we present an evidence-based review on the impact of the COVID-19 pandemic on spinal surgery and our current knowledge about this issue. We conducted a thorough search of the PubMed, Medline, and Google Scholar databases using the keywords, \"COVID-19,\" \"COVID-19 impact on spine surgery,\" \"coronavirus impact on spine surgery,\" \"COVID-19 impact on neurosurgery,\" \"coronavirus impact on neurosurgery,\" \"COVID-19 impact on spine surgeons,\" and \"coronavirus impact on spine surgeons\" on May 6, 2020. A total of 8,322 articles were identified in the initial search. Articles that were duplicated, those that did not pertain to COVID-19 or spine surgeries, those with details not pertaining to the current topic of interest, and those published in languages other than English were excluded from our analyses. After complete screening, six articles were included in this review. During the previous few weeks, the COVID pandemic has significantly influenced all major aspects of spine surgery across the world. Outpatient care has been gradually shifted from physical visits to tele-health and online consultations. General recommendations have favored the conservative approach over surgeries, although no patient should be deprived of standard care owing to concerns about COVID. The general principles followed by spine surgeons should include early detection of COVID symptomatology; triaging of patients based on underlying spinal pathology; prescription of appropriate investigations to confirm the COVID status; isolation, as needed; selection of optimal management method as per the guidelines; adherence to best intraoperative practices; and ensuring protective measures for non-infected patients, family members, fellow heath care providers, and themselves against the disease.", "qid": 11, "docid": "notvvhe4", "rank": 15, "score": 8.107399940490723}, {"content": "Title: Principles for Managing Patients with Spinal Ailments in the Coronavirus Disease 2019 Era: What Do We Know So Far? An Evidence-Based, Narrative Review. Content: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected all specialty practices in medicine, including the field of spinal surgery. Spinal surgery is unique in that the procedures include not only fully elective and fully emergent interventions, but also involve a separate group of semi-emergent surgeries, where delayed intervention may lead to permanent neurological deficits. Here, we present an evidence-based review on the impact of the COVID-19 pandemic on spinal surgery and our current knowledge about this issue. We conducted a thorough search of the PubMed, Medline, and Google Scholar databases using the keywords, \"COVID-19,\" \"COVID-19 impact on spine surgery,\" \"coronavirus impact on spine surgery,\" \"COVID-19 impact on neurosurgery,\" \"coronavirus impact on neurosurgery,\" \"COVID-19 impact on spine surgeons,\" and \"coronavirus impact on spine surgeons\" on May 6, 2020. A total of 8,322 articles were identified in the initial search. Articles that were duplicated, those that did not pertain to COVID-19 or spine surgeries, those with details not pertaining to the current topic of interest, and those published in languages other than English were excluded from our analyses. After complete screening, six articles were included in this review. During the previous few weeks, the COVID pandemic has significantly influenced all major aspects of spine surgery across the world. Outpatient care has been gradually shifted from physical visits to tele-health and online consultations. General recommendations have favored the conservative approach over surgeries, although no patient should be deprived of standard care owing to concerns about COVID. The general principles followed by spine surgeons should include early detection of COVID symptomatology; triaging of patients based on underlying spinal pathology; prescription of appropriate investigations to confirm the COVID status; isolation, as needed; selection of optimal management method as per the guidelines; adherence to best intraoperative practices; and ensuring protective measures for non-infected patients, family members, fellow heath care providers, and themselves against the disease.", "qid": 11, "docid": "ve1vlm1c", "rank": 16, "score": 8.107398986816406}, {"content": "Title: Surgical care of thoracic malignancies during the COVID-19 pandemic in M\u00e9xico: An expert consensus guideline from the Sociedad Mexicana de Oncolog\u00eda (SMeO) and the Sociedad Mexicana de Cirujanos Tor\u00e1cicos Generales (SMCTG) Content: To date, the impact, timeline and duration of COVID-19 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID-19 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID-19 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico.", "qid": 11, "docid": "nbrltocp", "rank": 17, "score": 8.023300170898438}, {"content": "Title: Surgical care of thoracic malignancies during the COVID\u201019 pandemic in M\u00e9xico: An expert consensus guideline from the Sociedad Mexicana de Oncolog\u00eda (SMeO) and the Sociedad Mexicana de Cirujanos Tor\u00e1cicos Generales (SMCTG) Content: To date, the impact, timeline and duration of COVID\u201019 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID\u201019 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID\u201019 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico.", "qid": 11, "docid": "wrr3oief", "rank": 18, "score": 8.023299217224121}, {"content": "Title: The Critical Care Society of Southern Africa Consensus Statement on ICU Triage and Rationing (ConICTri). Content: Background. In South Africa (SA), intensive care is faced with the challenge of resource scarcity as well as an increasing demand for intensive care unit (ICU) services. ICU services are expensive, and practitioners in low- to middle-income countries experience daily the consequences of limited resources. Critically limited resources necessitate that rationing and triage (prioritisation) decisions are frequently necessary in SA, particularly in the publicly funded health sector. Purpose. The purpose of this consensus statement is to examine key questions that arise when considering the status of ICU resources in SA, and more specifically ICU admission, rationing and triage decisions. The accompanying guideline in this issue is intended to guide frontline triage policy and ensure the best utilisation of intensive care in SA, while maintaining a fair distribution of available resources. Fair and efficient triage is important to ensure the ongoing provision of high-quality care to adult patients referred for intensive care. Recommendations. In response to 14 key questions developed using a modified Delphi technique, 29 recommendations were formulated and graded using an adapted GRADE score. The 14 key questions addressed the status of the provision of ICU services in SA, the degree of resource restriction, the efficiency of resource management, the need for triage, and how triage could be most justly implemented. Important recommendations included the need to formally recognise and accurately quantify the provision of ICU services in SA by national audit; actively seek additional resources from governmental bodies; consider methods to maximise the efficiency of ICU care; evaluate lower level of care alternatives; develop a triage guideline to assist policy-makers and frontline practitioners to implement triage decisions in an efficient and fair way; measure and audit the consequence of triage; and promote research to improve the accuracy and consistency of triage decisions. The consensus document and guideline should be reviewed and revised appropriately within 5 years. Conclusion. In recognition of the absolute need to limit patient access to ICU because of the lack of sufficient intensive care resources in public hospitals, recommendations and a guideline have been developed to guide policy-making and assist frontline triage decision-making in SA. These documents are not a complete plan for quality practice but rather the beginning of a long-term initiative to engage clinicians, the public and administrators in appropriate.", "qid": 11, "docid": "8f5gryzk", "rank": 19, "score": 7.996799945831299}, {"content": "Title: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival Content: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. \"First come, first served\" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "qid": 11, "docid": "mu0g857x", "rank": 20, "score": 7.970099925994873}, {"content": "Title: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival Content: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world\u2019s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. \u201cFirst come, first served\u201d is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "qid": 11, "docid": "x0me00m0", "rank": 21, "score": 7.970098972320557}, {"content": "Title: Endocrine surgery in the Coronavirus disease 2019 pandemic: Surgical Triage Guidelines Content: BACKGROUND: In the face of the COVID\u201019 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. METHODS: An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID\u201019, aligned with phases of care published by the ACS. RESULTS: Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. CONCLUSIONS: These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID\u201019.", "qid": 11, "docid": "tgm90lbp", "rank": 22, "score": 7.936800003051758}, {"content": "Title: Endocrine surgery in the Coronavirus disease 2019 pandemic: Surgical Triage Guidelines Content: BACKGROUND: In the face of the COVID-19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. METHODS: An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID-19, aligned with phases of care published by the ACS. RESULTS: Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. CONCLUSIONS: These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID-19.", "qid": 11, "docid": "vc2i6auz", "rank": 23, "score": 7.936799049377441}, {"content": "Title: Valvular and structural heart disease management during the COVID-19 pandemic. Expert opinion of the Working Group on Valvular Heart Diseases, the Working Group on Cardiac Surgery, and the Association of Cardiovascular Interventions of the Polish Cardiac Society. Content: Ongoing pandemics of SARS-CoV-2 coronavirus disease 2019 (COVID-19) represents a major challenge for healthcare. Beside the proven involvement of cardiovascular system in COVID-19, increased healthcare system resources are redirected towards handling infected patients and thus induce major changes in access to services and priorities in the management of patients with unrelated chronic cardiovascular disease. This document, created by task force involving Working Groups on Valvular Heart Disease and Cardiac Surgery as well as Association of Cardiovascular Intervention, Polish Cardiac Society proposes modifications of diagnostic pathways, principles of healthcare professionals protection and guidelines for treatment according to triage and prioritization. Valvular heart teams should continue working with utilization of telemedicine and digital technology. Diagnostic tests must be simplified or deferred to minimize potentially dangerous aerosol generating procedures such as transesophageal echocardiography or exercise imaging. Treatments for aortic stenosis and mitral regurgitation have to be offered especially in urgent indications and in patients with advanced disease and poor prognosis. Expert risk stratification is essential for triage and setting the priority lists. In any case, appropriate level of personal protection must be ensured for healthcare personnel to prevent spreading infections and preserving specialized manpower to supply for the continuing need of handling chronic serious cardiovascular disease. Importantly, as soon as the local epidemic situation improves, efforts must be made to rebuild standard opportunities for elective treatment of valvular heart disease and occluder-based therapies according to existing guidelines, thus rebuilding stat-of-the-art cardiovascular services.", "qid": 11, "docid": "3qpptp62", "rank": 24, "score": 7.928800106048584}, {"content": "Title: Radiotherapeutic management of brain tumours during the COVID-19 pandemic Content: AIM: The coronavirus disease (COVID-19) pandemic is bound to put tremendous pressure on the existing healthcare system. This aim of this technical note is to help in triaging patients with brain tumours who are sent for radiotherapy during this pandemic and to provide safe and evidence-based care. MATERIALS AND METHODS: Published data for this review were identified by systematically searching PubMed database from November 2007 onwards with the following Medical Subject Heading (Mesh) terms \u2018Brain tumours\u2019, \u2018COVID-19\u2019, \u2018coronavirus\u2019, \u2018SARS-nCoV-2\u2019, \u2018Radiotherapy\u2019, \u2018Guidelines\u2019 \u2018hypofractionation\u2019 using Boolean search algorithm. Articles in English language were reviewed. RESULTS: We tried to apply the as low as reasonable achievable (ALARA) principle in triaging and management of patients for radiotherapy. We identified protocols which have hypofractionated regimens (reducing patient visits to hospital, time spent in treatment console) with similar outcomes when compared to conventional fractionated regimens and not overburdening the healthcare facility. We also identified the tumours for which we could safely avoid or delay the initiation of radiotherapy. CONCLUSION: Treatment decisions made during the COVID-19 pandemic rely on the safety first/do no harm principle and evidence-based prioritisation of cases for triage. This article is a tool to aid in triaging and prioritising brain tumour patient management. This is for consideration during the pandemic only and certainly not as a strategy for permanent practice change.", "qid": 11, "docid": "v8mprtro", "rank": 25, "score": 7.895699977874756}, {"content": "Title: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the COVID-19 Pandemic: An ACC/SCAI Position Statement Content: The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.", "qid": 11, "docid": "hzi8zuyt", "rank": 26, "score": 7.82919979095459}, {"content": "Title: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement Content: Abstract The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.", "qid": 11, "docid": "l8vkzbh0", "rank": 27, "score": 7.829198837280273}, {"content": "Title: Rapid De-Escalation and Triaging Patients in Community-Based Palliative Care Content: Abstract Context The COVID-19 pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? Measures The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment (PPE) resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. Conclusions/Lessons Learned We recommend active triaging, communication, frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.", "qid": 11, "docid": "qskqikk9", "rank": 28, "score": 7.794899940490723}, {"content": "Title: Lives on the line? Ethics and practicalities of duty of care in pandemics and disasters. Content: Pandemics and acute emergencies raise pressing medical, ethical and organisational challenges. These include global governance, priority setting, triaging of patients, allocation of scarce resources and restricting individual liberty in the interests of public health. We will focus particularly on an issue of direct relevance to all respiratory team members, i.e. what is the duty of the healthcare worker to continue working in the face of personal risk, and draw lessons from guidelines, ethical considerations, past pandemics and evolving experience with H1N1 swine influenza.", "qid": 11, "docid": "02tomttb", "rank": 29, "score": 7.794300079345703}, {"content": "Title: COVID-19 Pandemic: Consensus guidelines for preferred practices in an aesthetic clinic Content: Strict infection control measures in response to the current COVID-19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS-CoV-2 infection. Consensus guidelines for \"preferred practices\" were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low-risk, moderate risk, and high-risk based on the likelihood of transmission of SARS-CoV-2 virus from the patient to the treating physician or therapist. While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID-19 infection in aesthetic clinics.", "qid": 11, "docid": "h822qpja", "rank": 30, "score": 7.774400234222412}, {"content": "Title: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement. Content: The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.", "qid": 11, "docid": "y50ou7gg", "rank": 31, "score": 7.774399280548096}, {"content": "Title: Clinical and Ethical Considerations in Allocation of Ventilators in an Influenza Pandemic or Other Public Health Disaster: A Comparison of the 2007 and 2015 New York State Ventilator Allocation Guidelines. Content: OBJECTIVE During an influenza or COVID-19 pandemic that results in acute respiratory distress, available ventilators will not meet demand. In 2007, the NYS Task Force on Life and the Law and Department of Health released draft Guidelines for ethical allocation of ventilators for adults. In 2015, updated guidelines were released to ensure that: (1) revisions reflect the public's values and (2) the triage protocol is substantiated by evidence-based clinical data. We summarize the development and content of the 2015 Guidelines compared to the 2007 version, emphasizing new/revised aspects of the ethical considerations and clinical protocol. METHODS We compared the 2007 and 2015 guidelines, with particular emphasis on the ethical issues and clinical protocols. RESULTS The 2015 Guidelines retained much of the ethical and clinical framework of the 2007 draft. The triage protocol was revised using evidence-based clinical data. Patients with the highest likelihood of short-term survival with ventilator therapy have priority access. Protocol consists of exclusion criteria, the sequential organ failure assessment (SOFA) score, and periodic clinical assessments. Guidance is provided on secondary triage criteria. Other forms of medical intervention/palliative care and review of triage decisions are discussed. CONCLUSIONS The 2015 Guidelines reflect advances in medicine and societal values and provide an evidenced-based framework to save the most lives. The framework could be adapted in other emergencies, such as the COVID-19 pandemic, that require ventilators.", "qid": 11, "docid": "fgnrujsf", "rank": 32, "score": 7.749599933624268}, {"content": "Title: COVID\u201019 Pandemic: Consensus Guidelines for Preferred Practices in an Aesthetic Clinic Content: BACKGROUND: Strict infection control measures in response to the current COVID\u201019 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. METHODS: An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS\u2010CoV\u20102 infection. RESULTS: Consensus guidelines for \u2018preferred practices' were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low\u2010risk, moderate risk, and high\u2010risk based on the likelihood of transmission of SARS\u2010CoV\u20102 virus from the patient to the treating physician or therapist. CONCLUSIONS: While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID\u201019 infection in aesthetic clinics. This article is protected by copyright. All rights reserved.", "qid": 11, "docid": "6mzzibj8", "rank": 33, "score": 7.676000118255615}, {"content": "Title: Sustainable practice of ophthalmology during COVID-19: challenges and solutions Content: PURPOSE: The Coronavirus (COVID-19) outbreak is rapidly emerging as a global health threat. With no proven vaccination or treatment, infection control measures are paramount. In this article, we aim to describe the impact of COVID-19 on our practice and share our strategies and guidelines to maintain a sustainable ophthalmology practice. METHODS: Tan Tock Seng Hospital (TTSH) Eye Centre is the only ophthalmology department supporting the National Centre for Infectious Diseases (NCID), which is the national screening center and the main center for management of COVID-19 patients in Singapore. Our guidelines during this outbreak are discussed. RESULTS: Challenges in different care settings in our ophthalmology practice have been identified and analyzed with practical solutions and guidelines implemented in anticipation of these challenges. First, to minimize cross-infection of COVID-19, stringent infection control measures were set up. These include personal protective equipment (PPE) for healthcare workers and routine cleaning of \u201chigh-touch\u201d surfaces. Second, for outpatient care, a stringent dual screening and triaging process were carried out to identify high-risk patients, with proper isolation for such patients. Administrative measures to lower patient attendance and reschedule appointments were carried out. Third, inpatient and outpatient care were separated to minimize interactions. Last but not least, logistics and manpower plans were drawn up in anticipation of resource demands and measures to improve the mental well-being of staff were implemented. CONCLUSION: We hope our measures during this COVID-19 pandemic can help ophthalmologists globally and serve to guide and maintain safe access in ophthalmology clinics when faced with similar disease outbreaks.", "qid": 11, "docid": "la5lk7of", "rank": 34, "score": 7.671199798583984}, {"content": "Title: Sustainable practice of ophthalmology during COVID-19: challenges and solutions Content: PURPOSE: The Coronavirus (COVID-19) outbreak is rapidly emerging as a global health threat. With no proven vaccination or treatment, infection control measures are paramount. In this article, we aim to describe the impact of COVID-19 on our practice and share our strategies and guidelines to maintain a sustainable ophthalmology practice. METHODS: Tan Tock Seng Hospital (TTSH) Eye Centre is the only ophthalmology department supporting the National Centre for Infectious Diseases (NCID), which is the national screening center and the main center for management of COVID-19 patients in Singapore. Our guidelines during this outbreak are discussed. RESULTS: Challenges in different care settings in our ophthalmology practice have been identified and analyzed with practical solutions and guidelines implemented in anticipation of these challenges. First, to minimize cross-infection of COVID-19, stringent infection control measures were set up. These include personal protective equipment (PPE) for healthcare workers and routine cleaning of \"high-touch\" surfaces. Second, for outpatient care, a stringent dual screening and triaging process were carried out to identify high-risk patients, with proper isolation for such patients. Administrative measures to lower patient attendance and reschedule appointments were carried out. Third, inpatient and outpatient care were separated to minimize interactions. Last but not least, logistics and manpower plans were drawn up in anticipation of resource demands and measures to improve the mental well-being of staff were implemented. CONCLUSION: We hope our measures during this COVID-19 pandemic can help ophthalmologists globally and serve to guide and maintain safe access in ophthalmology clinics when faced with similar disease outbreaks.", "qid": 11, "docid": "mt4f2p21", "rank": 35, "score": 7.671198844909668}, {"content": "Title: Recommendations for Dental Care during COVID-19 Pandemic. Content: Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.", "qid": 11, "docid": "qqqu1adu", "rank": 36, "score": 7.639100074768066}, {"content": "Title: Triaging of Respiratory Protective Equipment on the assumed risk of SARS-CoV-2 aerosol exposure in patient-facing healthcare workers delivering secondary care: a rapid review Content: ABSTRACT BACKGROUND Objectives: \"In patient-facing healthcare workers delivering secondary care, what is the evidence behind UK Government PPE Guidance on surgical masks versus respirators for SARS-CoV-2 protection?\" METHODS Two independent reviewers searched MEDLINE, Google Scholar and grey literature 11th-30th April 2020. Studies published on any date containing primary data comparing surgical facemasks and respirators specific to SARS-CoV-2, and studies underpinning government PPE guidance, were included. Appraisal was performed using CASP checklists. Results were synthesised by comparison of findings and appraisals. RESULTS In all three laboratory studies of 14 different respirators and 12 surgical facemasks, respirators were significantly more effective than facemasks in protection factors, reduction factors, filter penetrations, and total inspiratory leakages at differing particle sizes, mean inspiratory flows, and breathing rates. Tests included live viruses and inert particles on dummies and humans. In six clinical studies, 6,502 participants, there was no consistent definition of \"exposure\" to determine the efficacy of RPE. It is difficult to define \"safe\". The only statistically significant result found continuous use of respirators more effective in clinical respiratory illness compared to targeted use or surgical facemask. CONCLUSIONS There is a paucity of evidence on the comparison of FRSMs and respirators specific to SARS-CoV-2, and poor-quality evidence in other contexts. Indirectness results in extrapolation of non-SARS-CoV-2 specific data to guide UK Government PPE guidance. The appropriateness of this is unknown given the uncertainty over the transmission of SARS-CoV-2. 1. The evidence base for UK Government PPE guidelines is not based on SARS-CoV-2 and requires generalisation from low-quality evidence of other pathogens/particles. 2. There is a paucity of high-quality evidence regarding the efficacy of RPE specific to SARS-CoV-2. 3. HMG's PPE guidelines are underpinned by the assumption of droplet transmission of SARS-CoV-2. Triaging the use of FFP3 respirators might increase the risk of COVID-19 faced by some. FUNDING This review was unfunded and unsponsored.", "qid": 11, "docid": "cvw6e832", "rank": 37, "score": 7.615099906921387}, {"content": "Title: Ethical Framework for Nutrition Support Resource Allocation During Shortages: Lessons From COVID-19 Content: The coronavirus disease 2019 (COVID-19) pandemic has impacted all aspects of our population. The \"Troubling Trichotomy\" of what can be done technologically, what should be done ethically, and what must be done legally is a reality during these unusual circumstances. Recent ethical considerations regarding allocation of scarce resources, such as mechanical ventilators, have been proposed. These can apply to other disciplines such as nutrition support, although decisions regarding nutrition support have a diminished potential for devastating outcomes. The principal values and goals leading to an ethical framework for a uniform, fair, and objective approach are reviewed in this article, with a focus on nutrition support. Some historical aspects of shortages in nutrition supplies and products during normal circumstances, as well as others during national crises, are outlined. The development and implementation of protocols using a scoring system seems best addressed by multidisciplinary ethics and triage committees with synergistic but disparate functions. Triage committees should alleviate the burdens of unilateral decisions by the healthcare team caring for patients. The treating team should make every attempt to have patients and the public at large update or execute/develop advance directives. Legal considerations, as the third component of the Troubling Trichotomy, are of some concern when rationing care. The likelihood that criminal or civil charges could be brought against individual healthcare professionals or institutions can be minimized, if fair protocols are uniformly applied and deliberations well documented.", "qid": 11, "docid": "2onxj1oe", "rank": 38, "score": 7.59660005569458}, {"content": "Title: Ethical Framework for Nutrition Support Resource Allocation During Shortages: Lessons From COVID\u201019 Content: The coronavirus disease (COVID\u201019) pandemic has impacted all aspects of our population. The \u201cTroubling Trichotomy\u201d of what can be done technologically, what should be done ethically, and what must be done legally is a reality during these unusual circumstances. Recent ethical considerations regarding allocation of scarce resources, such as mechanical ventilators, have been proposed. These can apply to other disciplines such as nutrition support, although decisions regarding nutrition support have a diminished potential for devastating outcomes. The principal values and goals leading to an ethical framework for a uniform, fair, and objective approach are reviewed in this article, with a focus on nutrition support. Some historical aspects of shortages in nutrition supplies and products during normal circumstances, as well as others during national crises, are outlined. The development and implementation of protocols using a scoring system seems best addressed by multidisciplinary ethics and triage committees with synergistic but disparate functions. Triage committees should alleviate the burdens of unilateral decisions by the healthcare team caring for patients. The treating team should make every attempt to have patients and the public at large update or execute/develop advance directives. Legal considerations, as the third component of the Troubling Trichotomy, are of some concern when rationing care. The likelihood that criminal or civil charges could be brought against individual healthcare professionals or institutions can be minimized, if fair protocols are uniformly applied and deliberations well documented.", "qid": 11, "docid": "w10y5sf9", "rank": 39, "score": 7.596599102020264}, {"content": "Title: Recommendations for the organization of electrophysiology and cardiac pacing services during the COVID-19 pandemic : Latin American Heart Rhythm Society (LAHRS) in collaboration with: Colombian College Of Electrophysiology, Argentinian Society of Cardiac Electrophysiology (SADEC), Brazilian Society Of Cardiac Arrhythmias (SOBRAC), Mexican Society Of Cardiac Electrophysiology (SOMEEC) Content: COVID-19 is a rapidly evolving public health emergency that has largely impacted the provision of healthcare services around the world. The challenge for electrophysiology teams is double; on one side preventing disease spread by limiting all nonessential face-to-face interactions, but at the same time ensuring continued care for patients who need it. These guidelines contain recommendations regarding triaging in order to define what procedures, device checks and clinic visits can be postponed during the pandemic. We also discuss best practices to protect patients and healthcare workers and provide guidance for the management of COVID-19 patients with arrhythmic conditions.", "qid": 11, "docid": "7jxwn2y6", "rank": 40, "score": 7.578400135040283}, {"content": "Title: Recommendations for the organization of electrophysiology and cardiac pacing services during the COVID-19 pandemic: Latin American Heart Rhythm Society (LAHRS) in collaboration with: Colombian College Of Electrophysiology, Argentinian Society of Cardiac Electrophysiology (SADEC), Brazilian Society Of Cardiac Arrhythmias (SOBRAC), Mexican Society Of Cardiac Electrophysiology (SOMEEC) Content: COVID-19 is a rapidly evolving public health emergency that has largely impacted the provision of healthcare services around the world. The challenge for electrophysiology teams is double; on one side preventing disease spread by limiting all nonessential face-to-face interactions, but at the same time ensuring continued care for patients who need it. These guidelines contain recommendations regarding triaging in order to define what procedures, device checks and clinic visits can be postponed during the pandemic. We also discuss best practices to protect patients and healthcare workers and provide guidance for the management of COVID-19 patients with arrhythmic conditions.", "qid": 11, "docid": "wydt1ykq", "rank": 41, "score": 7.578399181365967}, {"content": "Title: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists Content: Abstract Context The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Objective To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. Evidence acquisition A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. Evidence synthesis A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. Conclusions PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes.", "qid": 11, "docid": "bsbz3a1l", "rank": 42, "score": 7.497099876403809}, {"content": "Title: Head and neck surgical oncology in the time of a pandemic: Subsite-specific triage guidelines during the COVID-19 pandemic Content: BACKGROUND: COVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel. METHODS: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular. RECOMMENDATIONS: Each subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred. CONCLUSION: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.", "qid": 11, "docid": "3fs7r79z", "rank": 43, "score": 7.457099914550781}, {"content": "Title: Head and neck surgical oncology in the time of a pandemic: Subsite\u2010specific triage guidelines during the COVID\u201019 pandemic Content: BACKGROUND: COVID\u201019 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel. METHODS: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular. RECOMMENDATIONS: Each subsite is presented separately with disease\u2010specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred. CONCLUSION: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID\u201019 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.", "qid": 11, "docid": "tbxjodu0", "rank": 44, "score": 7.457098960876465}, {"content": "Title: Diagnosis and rational approach to emergency vascular surgery in the shadow of novel coronavirus pneumonia/ \u4e2d\u534e\u666e\u901a\u5916\u79d1\u6742\u5fd7 Content: Objective@#To explore a safe, effective and rapid rescue method and key points for the management of vascular surgical emergencies in an area under guaranting Covid-19 (corona virus disease 2019) .@*Methods@#Under the guidance of COVID-19 diagnosis and treatment guidelines , 4 cases of vascular surgical emergency patients admitted to our department from Feb 1 to Feb 10, 2020 were screened for COVID-19 and given emergency vascular surgical treatment.@*Results@#Two patients had acute thoracic aortic dissection, one patient had acute left foot ulcer with infection, one patient had severe carotid artery stenosis and frequent TIA. All patients were diagnosed quickly according to the three-level triage process. Endovascular repair (TEVAR) was performed in 2 cases, carotid stenting in 1 case, and left foot amputation in 1 case. Two patients running postoperative fever below 38\u2103 were safely excluded COVID-19 and cured. There were no other major morbidities nor mortality.@*Conclusions@#Under the COVID-19 prevention and control guidelines, the establishing of a comprehensive prevention and control system of patient-medicine-care-management helps to perform confine operation on vascular surgical emergency.", "qid": 11, "docid": "kyvggk83", "rank": 45, "score": 7.410900115966797}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 11, "docid": "5gd0q8yq", "rank": 46, "score": 7.4045000076293945}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care. Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 11, "docid": "nj0ue2c2", "rank": 47, "score": 7.404499053955078}, {"content": "Title: Way Forward: Gastrointestinal Tract Endoscopy Work Flow Postlockdown Era Content: Gastrointestinal tract endoscopy being an aerosol generating procedure increases the risk to staff and uninfected patients from a coronavirus disease 2019 patient. Social and physical distancing through \u201clockdown\u201d has suppressed the spread of disease but will not eradicate it. Various endoscopy societies formulated guidelines to triage the patients and limit the work to only emergency and urgent cases and postpone \u201croutine\u201d endoscopies. Postlockdown infected vector pool will persist till an effective vaccine is widely available. Nonurgent cases cannot be postponed indefinitely. We need to identify infected symptomatic and asymptomatic individuals and create a safe environment for uninfected patients. Endoscopy staff protection through education, optimized manpower flow, and personal protective equipment usage and hand hygiene needs urgent attention. Proper environment sanitization, endoscope, and device reprocessing will remain important.", "qid": 11, "docid": "sqqxvqi8", "rank": 48, "score": 7.394199848175049}, {"content": "Title: Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review Content: Importance: During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. Objective: To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. Evidence Review: This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. Findings: As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). Conclusions and Relevance: These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.", "qid": 11, "docid": "m7761w4f", "rank": 49, "score": 7.39169979095459}, {"content": "Title: Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review Content: IMPORTANCE: During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. OBJECTIVE: To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. EVIDENCE REVIEW: This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. FINDINGS: As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). CONCLUSIONS AND RELEVANCE: These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.", "qid": 11, "docid": "ocd2i2j6", "rank": 50, "score": 7.391698837280273}, {"content": "Title: [Bioethics guide on scarce medical resource allocation in Mexico]. Content: The bioethical inquiry about allocating fairly scarce health resources is not new, all countries around the world that were seriously afflicted by SARS-CoV-2 have issued triage guidelines in order to address the dilemmas raised by the pandemic. There is no question about the need to create bioethical guidelines, since its creation provides a degree of certainty that fair and ethical decisions are taken. This also prevents that decisions are made in solitary and maybe motivated by corrupted actions. In Mexico, the creation of this guidelines was a proactive and preventive measure to what was unavoidable, the exponential contagion phase of the pandemical scenario caused by Covid-19. On April 30, 2020 the General Sanitary Council published the Bioethical Guide to Allocate Scarce Resources on Critical Care Medicine in Emergency Situation. This guide has at the core of its principal that of upmost importance: social justice principle which main thesis is \"All lives have the same value\". The aim of this contribution is to provide the ethical and legal principles established in the aforementioned bioethical guideline. In sum, a brief exploration of the ethical reasons that supports a specific way to allocate scarce health resources is provided, as well as the foundations of the procedural part from a human rights-based approach.", "qid": 11, "docid": "0u56njnr", "rank": 51, "score": 7.383600234985352}, {"content": "Title: Dermatological consultations in the COVID-19 era: is teledermatology the key to social distancing? An Egyptian experience Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has received marked attention globally. A worldwide call for social distancing occurred. Although the reduction of face-to-face consultation is required in order to reduce the risk of infection, dermatological services must be maintained in action and 'teledermatology' should be the solution. Materials & methods: We introduce a cross sectional observational study, demonstrating the patients' behavior regarding dermatological consultations in Cairo, Egypt in both private and Public practice. Synchronous (live interaction via What's app and Zoom) and asynchronous (What's app, emails) teledermatology models were used. After the end of the teleconsultation, patients were asked to fill a questionnaire adapted from the Telehealth Usability Questionnaire (TUQ). RESULTS: There was an overall satisfaction and future use score among the interviewed patients that received Teledermatology services of 91.0%, a usefulness score of 93.7%, interface and interaction quality scores of 85.9% and 87.0%, ease and use learnability score of 87.8% and reliability score of 86.7%. CONCLUSION: Teledermatology was efficient in triaging and treatment, hence, decreasing risk of COVID-19 exposure for the physician, the patient and the paramedical personel in heavily populated third world countries. Legislation is needed to sanction physician compensation for tele dermatology where this does not exist.", "qid": 11, "docid": "bxbfmyx8", "rank": 52, "score": 7.338799953460693}, {"content": "Title: Dermatological consultations in the COVID-19 era: Is teledermatology the key to social distancing? An Egyptian experience. Content: Background: Coronavirus disease 2019 (COVID-19) has received marked attention globally. A worldwide call for social distancing occurred. Although the reduction of face-to-face consultation is required in order to reduce the risk of infection, dermatological services must be maintained in action and \"teledermatology\" should be the solution.Materials & Methods: We introduce a cross sectional observational study, demonstrating the patients' behavior regarding dermatological consultations in Cairo, Egypt in both private and Public practice. Synchronous (live interaction via What's app and Zoom) and asynchronous (What's app, emails) teledermatology models were used. After the end of the teleconsultation, patients were asked to fill a questionnaire adapted from the Telehealth Usability Questionnaire (TUQ)Results: There was an overall satisfaction and future use score among the interviewed patients that received Teledermatology services of 91.0%, a usefulness score of 93.7%, interface and interaction quality scores of 85.9% and 87.0%, ease and use learnability score of 87.8% and reliability score of 86.7%.Conclusion: Teledermatology was efficient in triaging and treatment, hence, decreasing risk of COVID-19 exposure for the physician, the patient and the paramedical personel in heavily populated third world countries. Legislation is needed to sanction physician compensation for tele dermatology where this does not exist.", "qid": 11, "docid": "h0nzsla0", "rank": 53, "score": 7.338798999786377}, {"content": "Title: [What are the highlights of \"Diagnosis and treatment of Disease 2019 novel coronavirus infection suitable for Military support Hubei medical team\"]. Content: Thousands of medical workers in the Military support Hubei medical team are exerting themselves in many hospitals in Hubei Province. They are diligent in treating patients, at the same time, they constantly summarize experience and combine the characteristics of military hospitals. According to \" the Diagnosis and Treatment of New Coronavirus Pneumonia \"(6th edition) of the National Health Commission of the People's Republic of China, a new guideline for the diagnosis and treatment of 2019 novel coronavirus infection suitable for the military (first trial version) was established. Some unique opinions and suggestions are put forward in terms of disease name, diagnosis criteria, antiviral treatment, glucocorticoid application, etc. This article will make a proper interpretation in order to understand the guideline better and help guide the diagnosis and treatment of diseases.", "qid": 11, "docid": "prozgpn8", "rank": 54, "score": 7.285299777984619}, {"content": "Title: [What are the highlights of \"Diagnosis and treatment of disease 2019 novel coronavirus infection suitable for Military support Hubei medical team\"] Content: Thousands of medical workers in the Military support Hubei medical team are exerting themselves in many hospitals in Hubei Province. They are diligent in treating patients, at the same time, they constantly summarize experience and combine the characteristics of military hospitals. According to \"the Diagnosis and Treatment of New Coronavirus Pneumonia \"(6th edition) of the National Health Commission of the People's Republic of China, a new guideline for the diagnosis and treatment of 2019 novel coronavirus infection suitable for the military (first trial version) was established. Some unique opinions and suggestions are put forward in terms of disease name, diagnosis criteria, antiviral treatment, glucocorticoid application, etc. This article will make a proper interpretation in order to understand the guideline better and help guide the diagnosis and treatment of diseases.", "qid": 11, "docid": "w8qtzjbl", "rank": 55, "score": 7.285298824310303}, {"content": "Title: Transmission routes of SARS-CoV-2 and protective measures in dental clinics during the COVID-19 pandemic Content: RESULTS: The outbreak of coronavirus disease 2019 (COVID-19) has become a primary challenging public health issue for not only China but also the world On March 11, 2020, the World Health Organization declared that the pandemic of COVID-19 had become a public health emergency of global concern As of May 12, 2020 COVID-19 has been reported in over 180 countries/regions, with a total of 4,178,156 confirmed cases and over 280,000 deaths The risk of cross-infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be elevated between dental specialists and patients due to the peculiarity of dental practice Therefore, detailed and effective infection control measures are imminently needed to prevent nosocomial coronavirus infection This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics Classification schemes as well as color identification according to the results of the questionnaire survey and temperature measurement in precheck and triages are innovations proposed in this paper CLINICAL SIGNIFICANCE: This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics", "qid": 11, "docid": "au0sfe8g", "rank": 56, "score": 7.275100231170654}, {"content": "Title: Transmission routes of SARS-CoV-2 and protective measures in dental clinics during the COVID-19 pandemic. Content: RESULTS The outbreak of coronavirus disease 2019 (COVID-19) has become a primary challenging public health issue for not only China but also the world. On March 11, 2020, the World Health Organization declared that the pandemic of COVID-19 had become a public health emergency of global concern. As of May 12, 2020 COVID-19 has been reported in over 180 countries/regions, with a total of 4,178,156 confirmed cases and over 280,000 deaths. The risk of cross-infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be elevated between dental specialists and patients due to the peculiarity of dental practice. Therefore, detailed and effective infection control measures are imminently needed to prevent nosocomial coronavirus infection. This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics. Classification schemes as well as color identification according to the results of the questionnaire survey and temperature measurement in precheck and triages are innovations proposed in this paper. CLINICAL SIGNIFICANCE This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics.", "qid": 11, "docid": "jxi0mvbi", "rank": 57, "score": 7.275099277496338}, {"content": "Title: Ebola Preparedness in the Netherlands: The Need for Coordination Between the Public Health and the Curative Sector Content: CONTEXT: During the Ebola outbreak in West Africa in 2014-2015, close cooperation between the curative sector and the public health sector in the Netherlands was necessary for timely identification, referral, and investigation of patients with suspected Ebola virus disease (EVD). OBJECTIVE: In this study, we evaluated experiences in preparedness among stakeholders of both curative and public health sectors to formulate recommendations for optimizing preparedness protocols. Timeliness of referred patients with suspected EVD was used as indicator for preparedness. DESIGN: In focus group sessions and semistructured interviews, experiences of curative and public health stakeholders about the regional and national process of preparedness and response were listed. Timeliness recordings of all referred patients with suspected EVD (13) were collected from first date of illness until arrival in the referral academic hospital. RESULTS: Ebola preparedness was considered extensive compared with the risk of an actual patient, however necessary. Regional coordination varied between regions. More standardization of regional preparation and operational guidelines was requested, as well as nationally standardized contingency criteria, and the National Centre for Infectious Disease Control was expected to coordinate the development of these guidelines. For the timeliness of referred patients with suspected EVD, the median delay between first date of illness until triage was 2.0 days (range: 0-10 days), and between triage and arrival in the referral hospital, it was 5.0 hours (range: 2-7.5 hours). In none of these patients Ebola infection was confirmed. CONCLUSIONS: Coordination between the public health sector and the curative sector needs improvement to reduce delay in patient management in emerging infectious diseases. Standardization of preparedness and response practices, through guidelines for institutional preparedness and blueprints for regional and national coordination, is necessary, as preparedness for emerging infectious diseases needs a multidisciplinary approach overarching both the public health sector and the curative sector. In the Netherlands a national platform for preparedness is established, in which both the curative sector and public health sector participate, in order to implement the outcomes of this study.", "qid": 11, "docid": "9kw5r0bw", "rank": 58, "score": 7.2621002197265625}, {"content": "Title: Organizing a COVID-19 triage unit: a Swiss perspective Content: Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p < 0.001). Conclusion: Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "qid": 11, "docid": "holb6bk3", "rank": 59, "score": 7.259300231933594}, {"content": "Title: Organising a COVID-19 Triage Unit: a Swiss Perspective. Content: BACKGROUND With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. METHODS Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. OBSERVATIONS A total of 1,265 patients were screened between March 10th 2020 and April 12th 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p<0.001). CONCLUSION Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "qid": 11, "docid": "lom4jdcj", "rank": 60, "score": 7.259299278259277}, {"content": "Title: Gu\u00eda bio\u00e9tica de asignaci\u00f3n de recursos de medicina cr\u00edtica del Consejo de Salubridad General en M\u00e9xico./ [Bioethics guide on scarce medical resource allocation in Mexico] Content: The bioethical inquiry about allocating fairly scarce health resources is not new, all countries around the world that were seriously afflicted by SARS-CoV-2 have issued triage guidelines in order to address the dilemmas raised by the pandemic. There is no question about the need to create bioethical guidelines, since its creation provides a degree of certainty that fair and ethical decisions are taken. This also prevents that decisions are made in solitary and maybe motivated by corrupted actions. In Mexico, the creation of this guidelines was a proactive and preventive measure to what was unavoidable, the exponential contagion phase of the pandemical scenario caused by Covid-19. On April 30, 2020 the General Sanitary Council published the Bioethical Guide to Allocate Scarce Resources on Critical Care Medicine in Emergency Situation. This guide has at the core of its principal that of upmost importance: social justice principle which main thesis is \"All lives have the same value\". The aim of this contribution is to provide the ethical and legal principles established in the aforementioned bioethical guideline. In sum, a brief exploration of the ethical reasons that supports a specific way to allocate scarce health resources is provided, as well as the foundations of the procedural part from a human rights-based approach.", "qid": 11, "docid": "xp7fxceo", "rank": 61, "score": 7.2494001388549805}, {"content": "Title: Possibilities of telemedicine regarding the COVID-19 pandemic in light of the international and Hungarian experiences and recommendations Content: The COVID-19 outbreak was formally announced as a pandemic by WHO on the 11th of March, 2020. This attracts attention to the possibilities of telemedicine again. In support of stopping the spread of the novel coronavirus infection, whilst keeping the healthcare system running and minimizing the risk of being infected, we also need to find new ways, methods, and platforms to deal with this pandemic. By providing a literature overview and sharing practical guidelines, including the special example of Hungarian teledentistry, we present both international and Hungarian initiatives to involve telemedicine on different levels of healthcare systems regarding COVID-19. Both international and national data show that telemedicine can play a major role in the triage process, early identification, diagnosis and treatment of infected individuals, and management of patient pathways in a way that ensures the medical team does not come into contact with potentially infected patients. It also plays an important role in remote monitoring of medical conditions and care of patients with chronic diseases and reconnects vulnerable groups of healthcare personnel to the care system. In addition to the potential benefits of telemedicine, we must not forget the limitations of this method. However, it is important to emphasize that due to its wide availability, telemedicine services can provide sufficient flexibility for both primary and specialist care (outpatient and inpatient clinical care). For that very reason, it is an urgent need to define the national professional guidelines, legal and financing possibilities in this field in a long-term sustainable way.* Orv Hetil. 2020; 161(24): 983-992. *Disclaimer: We closed the writing of this manuscript on the 30th of April, 2020. The COVID-19 pandemic and related research studies still have been changing dynamically since then.", "qid": 11, "docid": "yxa8z17c", "rank": 62, "score": 7.238699913024902}, {"content": "Title: Impact of the coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation) Content: The Coronavirus (COVID-19) Pandemic represents a once in a century challenge to human healthcare with 2.4 million cases and 165,000 deaths thus far. Surgical practice has been significantly impacted with all specialties writing guidelines for how to manage during this crisis. All specialties have had to triage the urgency of their daily surgical procedures and consider non-surgical management options where possible. The Pandemic has had ramifications for ways of working, surgical techniques, open vs minimally invasive, theatre workflow, patient and staff safety, training and education. With guidelines specific to each specialty being implemented and followed, surgeons should be able to continue to provide safe and effective care to their patients during the COVID-19 pandemic. In this comprehensive and up to date review we assess changes to working practices through the lens of each surgical specialty.", "qid": 11, "docid": "dgysimh5", "rank": 63, "score": 7.222400188446045}, {"content": "Title: Proposed Modifications in the 6-minutue Walk Test for Potential Application in Patients with mild Coronavirus Disease 2019 (COVID-19): A Step to Optimize Triage Guidelines Content:", "qid": 11, "docid": "ss8yikca", "rank": 64, "score": 7.174300193786621}, {"content": "Title: Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation) Content: The Coronavirus (COVID-19) Pandemic represents a once in a century challenge to human healthcare with over 4.5 million cases and over 300,000 deaths thus far. Surgical practice has been significantly impacted with all specialties writing guidelines for how to manage during this crisis. All specialties have had to triage the urgency of their daily surgical procedures and consider non-surgical management options where possible. The Pandemic has had ramifications for ways of working, surgical techniques, open vs minimally invasive, theatre workflow, patient and staff safety, training and education. With guidelines specific to each specialty being implemented and followed, surgeons should be able to continue to provide safe and effective care to their patients during the COVID-19 pandemic. In this comprehensive and up to date review we assess changes to working practices through the lens of each surgical specialty.", "qid": 11, "docid": "m5oh91ha", "rank": 65, "score": 7.150700092315674}, {"content": "Title: Should Extremely Premature Babies Get Ventilators During the COVID-19 Crisis? Content: In a crisis, societal needs take precedence over a patient's best interests. Triage guidelines, however, differ on whether limited resources should focus on maximizing lives or life-years. Choosing between these two approaches has implications for neonatology. Neonatal units have ventilators, some adaptable for adults. This raises the question of whether, in crisis conditions, guidelines for treating extremely premature babies should be altered to free-up ventilators. Some adults who need ventilators will have a survival rate higher than some extremely premature babies. But surviving babies will likely live longer, maximizing life-years. Empiric evidence demonstrates that these babies can derive significant survival benefits from ventilation when compared to adults. When \"triaging\" or choosing between patients, justice demands fair guidelines. Premature babies do not deserve special consideration; they deserve equal consideration. Solidarity is crucial but must consider needs specific to patient populations and avoid biases against people with disabilities and extremely premature babies.", "qid": 11, "docid": "l3tmzksv", "rank": 66, "score": 7.144000053405762}, {"content": "Title: Policies and Guidelines for COVID-19 Preparedness: Experiences from the University of Washington Content: The Coronavirus Disease 2019 (COVID-19) pandemic initially presented in the United States in the greater Seattle area, and has rapidly progressed across the nation in the past 2 months, with the United States having the highest number of cases in the world. Radiology departments play a critical role in policy and guideline development both for the department and for the institutions, specifically in planning diagnostic screening, triage, and management of patients. In addition, radiology workflows, volumes and access must be optimized in preparation for the expected COVID-19 patient surges. This article discusses the processes that have been implemented at the University of Washington in managing the COVID-19 pandemic as well in preparing for patient surges, which may provide important guidance for other radiology departments who are in the early stages of preparation and management.", "qid": 11, "docid": "v9zrivd3", "rank": 67, "score": 7.132800102233887}, {"content": "Title: Does triage to critical care during a pandemic necessarily result in more survivors? Content: OBJECTIVE The 2009 H1N1 pandemic reinforced the need for a planned response to increased demand for critical care. Triage protocols have been proposed incorporating the exclusion of specified subgroups of patients from critical care. There have been no studies that explore the theoretical underpinning of triage at referral, and it is not clear under what circumstances triage would confer the intended benefits. We sought to explore the mechanisms whereby triage could lead to fewer deaths across a critical care population in the context of a pandemic. DESIGN We constructed a mathematical model based on queuing theory to compare the estimated short-term survival achieved by using a critical care service with and without triage at referral. Illustrative scenarios concerning a hypothetical critical care population were constructed to explore the roles of length of stay and critical care survival in determining the impact of triage and to identify \"tipping points\" of demand at which triage would result in more survivors. SETTING Not applicable as this was a data-free mathematical modeling exercise. MAIN RESULTS We identified circumstances in which triage would be expected to result in more survivors and circumstances in which it would not. In some scenarios, excluding patient groups solely on the basis of anticipated length of stay could be effective due to a more efficient use of critical care bed days. CONCLUSIONS The impact of triage is dependent on the level of demand and on the scale of achievable differences between included and excluded groups in terms of anticipated length of stay and critical care survival. It cannot be assumed that triage can or will result in fewer deaths. It should be remembered that there are considerations other than population-level short-term survival when determining the objectives of triage and its ethical implementation.", "qid": 11, "docid": "w0qs3lm1", "rank": 68, "score": 7.103400230407715}, {"content": "Title: [Interpretation of \"Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)\"]. Content: the National Health Commission of the People's Republic of China publish the guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 5) .With the awareness and understanding of the disease, the guidelines have been revised for recognize, treat, and prevent diseases. Then, what are the contents of the fifth edition of the guide issued updated compared to the fourth edition, now, learn together.", "qid": 11, "docid": "5wwlur3m", "rank": 69, "score": 7.100900173187256}, {"content": "Title: [Interpretation of \"Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)\"] Content: the National Health Commission of the People's Republic of China publish the guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 5) .With the awareness and understanding of the disease, the guidelines have been revised for recognize, treat, and prevent diseases. Then, what are the contents of the fifth edition of the guide issued updated compared to the fourth edition, now, learn together.", "qid": 11, "docid": "zt0s6vo8", "rank": 70, "score": 7.1008992195129395}, {"content": "Title: Interventional Stroke Care in the Era of COVID-19 Content: The current coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to immense strain on healthcare systems and workers. Patients with severe symptoms of COVID-19 may also present with acute neurological emergencies such as ischemic stroke. Ischemic stroke in these patients may result from COVID-19 related complications or decompensation of previously asymptomatic cerebrovascular disorders, or concurrent ischemic stroke from common stroke risk factors in a patient with COVID-19. Acute ischemic stroke patients with large vessel occlusions require emergent triage, intensive care, and mechanical thrombectomy. Management of patients with large vessel occlusions (LVO) requires special considerations in the current pandemic. Physicians must now account for prognosis of severe COVID-19, resource utilization, and risk of infection to healthcare workers when determining eligibility for mechanical thrombectomy (MT). Here, we describe important prognostic factors including age, laboratory, and imaging findings to consider for MT selection and provide suggestions for taking care of patients with LVO and possible or confirmed COVID-19. It is recommended to perform MT in patients within the established guidelines, and consider a conservative approach in cases where there is clinical equipoise to minimize futile reperfusion. Lastly, we describe an illustrative case of a patient with ischemic stroke and COVID-19.", "qid": 11, "docid": "hyevq5r0", "rank": 71, "score": 7.093800067901611}, {"content": "Title: Response of ophthalmologists in Israel to the novel coronavirus (2019-nCoV) outbreak Content: PURPOSE: The coronavirus disease (COVID-19) pandemic has evolved into a formidable healthcare crisis. Ophthalmologists are at daily personal risk of acquiring and transmitting the virus. Implementation of official practical and protective guidelines can be challenging and is often absent. The purpose of this study was to describe the status of ophthalmology practice in Israel, at the early stages of the outbreak. METHODS: A 17-item questionnaire was distributed to ophthalmologists practicing in Israel. Data was obtained regarding demographics and clinical and surgical practice during the pandemic. RESULTS: One hundred and sixty-seven ophthalmologists completed the survey from all regions of Israel. The survey was distributed during the early stages of the outbreak. At this time, no official government guidelines were in place. Most respondents reported no reduction of elective clinic visits and surgeries and no utilization of triage questionnaires. COVID-19 guidelines were reportedly promulgated to hospital ophthalmologists but not to community and private physicians. Personal protective equipment (PPE) measures were reportedly utilized; however, many respondents often acquired them individually. A majority of respondents advocated that healthcare institutions limit clinic and surgery services to emergency services. CONCLUSION: During the critical early stages of the COVID-19 outbreak in Israel, this study emphasizes the delay in development of emergency guidelines, necessary to protect patients and ophthalmologists from this highly transmissible disease.", "qid": 11, "docid": "9qls6bgw", "rank": 72, "score": 7.091599941253662}, {"content": "Title: Assessment of paediatric dental guidelines and caries management alternatives in the post COVID-19 period. A critical review and clinical recommendations Content: PURPOSE: The first aim of this paper is to provide dental professionals caring for children and adolescents during and after the COVID-19 pandemic with a reference to international dental guidelines. The second aim is to suggest minimally invasive treatment alternatives for caries management, minimising the risk of viral cross-infection and offering a safer clinical environment. METHODS: An evidence-based pertinent literature search of different electronic databases was performed in addition to leading global dental authorities, royal colleges, and programmes. RESULTS: All guidelines released in response to COVID-19 centred around minimising Aerosol Generating Procedures (AGP) impacting the provision of regular dental treatment of paediatric patients. There was an emphasis on triaging and only treating emergency and urgent cases. Special attention was given to medically compromised children in the guidelines. Detailed guidelines for the dental environment and equipment were given. This paper also summarised the relevant evidence-based guidelines for the use of non-invasive and minimally invasive caries management techniques. CONCLUSION: Specific recommendations for dental management of paediatric patients during and in the post-COVID-19 era are suggested. Minimisation of AGP procedures, and case-based selection of biological, non-invasive or minimally invasive methods are recommended.", "qid": 11, "docid": "oubaezfi", "rank": 73, "score": 7.047900199890137}, {"content": "Title: Cardiovascular disease in COVID-19: a systematic review and meta-analysis of 10,898 patients and proposal of a triage risk stratification tool Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has drastically affected global health. Despite several studies, there is yet a dearth of data regarding the mechanisms of cardiac injury, clinical presentation, risk factors, and treatment of COVID-19-associated cardiovascular disease. This systematic review and meta-analysis is aimed at defining the clinical, electrocardiographic, and pathologic spectrum of cardiovascular disease (CVD), frequency of elevated cardiac and inflammatory biomarkers, and their frequency and relationship with severity of the disease and mortality in COVID-19 patients and to develop a triage risk stratification tool (TRST) that can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy. We conducted an online search in databases of PubMed and Embase to identify relevant studies. Data selection was in concordance with PRISMA guidelines. Results were presented as pooled frequencies, odds ratio, standardized mean difference (SMD), and forest and funnel plots. RESULTS: We gathered a total of 54 studies and included 35 of them in our meta-analysis. Acute cardiac injury occurred in more than 25% of cases, mortality was 20 times higher, and admission to intensive care unit increased by 13.5 times. Hypertension was the most common pre-existing comorbidity with a frequency of 29.2%, followed by diabetes mellitus (13.5%). The deceased group of patients had higher cardiac and inflammatory biomarkers, with statistically significant SMD, compared with survivors. Pediatric patients were predominantly mildly affected. However, less frequently, the presentation was very similar to Kawasaki disease or Kawasaki shock syndrome. This latter presentation hass been called as multisystem inflammatory syndrome in children (MIS-C). CONCLUSIONS: There is a wide spectrum of cardiac involvement in COVID-19 patients, and hence a Triage Risk Stratification Tool can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy.", "qid": 11, "docid": "ynel6ore", "rank": 74, "score": 7.043700218200684}, {"content": "Title: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community Content: Abstract Background The coronavirus disease of 2019 (COVID-19) that is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020 with over 187,000 deaths. A growing body of evidence supports central nervous system (CNS) involvement. Methods We conducted a review of the literature for articles concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. Results CNS manifestations range from vague non-focal complaints to severe neurologic impairment associated with encephalitis. It is unclear whether neurological dysfunction is due to direct viral injury or systemic disease. The virus may affect brainstem pathways that lead to indirect respiratory dysfunction in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of ongoing scientific and clinical findings. Conclusions This review consolidates the current body of literature regarding the neurological impact of coronaviruses, discusses the reported neurologic manifestations of COVID-19, and highlights recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons are provided.", "qid": 11, "docid": "pocccocr", "rank": 75, "score": 7.035900115966797}, {"content": "Title: Crisis management of SARS in a hospital Content: Abstract Introduction: A large general hospital was suddenly disabled by an in-hospital outbreak of Severe Acute Respiratory Distress Syndrome (SARS). Method: The crisis was successfully managed by a Standard Operation Procedure (SOP) that included: (a) containment of SARS patients on a special floor and evacuation of the patients from the infected and near-around floors; (b) sorting of the hospital into areas and floors to avoid cross contact of people; (c) triage of patients into groups according to risks; (d) closure of the emergency room and outpatient clinics; and (e) set up of an outdoor fever screening station and emergency service. Results: The situation was quickly controlled after the implementation of these procedures. The central argument in this case is that crisis managerial behavior is the result of how managers channel and distribute the attention of their crisis sense. Impact on industry: What managers should do depends on what risk issues and actions related to risk independency, efficiency, safety priority, and transparency they take. What risk issues and actions they take depends on the crisis sense and on how management responds to leadership, resource, and execution.", "qid": 11, "docid": "2c114qbp", "rank": 76, "score": 7.029399871826172}, {"content": "Title: Ophthalmic Manifestations Of Coronavirus (COVID-19) Content: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] There have been several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis may be an ocular manifestation of SARS-CoV-2 infection A study conducted during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak detected SARS-CoV in tear samples in SARS patients in Singapore [2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions [3][[4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19 As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19 Indeed, one of the first providers to voice concerns regarding the spread of Coronavirus in Chinese patients was Li Wenliang, MD, an ophthalmologist He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission", "qid": 11, "docid": "vzxutyii", "rank": 77, "score": 7.015200138092041}, {"content": "Title: Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement. Content: BACKGROUND The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.", "qid": 11, "docid": "96mkzzh9", "rank": 78, "score": 7.012199878692627}, {"content": "Title: Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement Content: BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.", "qid": 11, "docid": "mm7amtch", "rank": 79, "score": 7.0121989250183105}, {"content": "Title: Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement Content: BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk\u2013benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.", "qid": 11, "docid": "qrcv4iuq", "rank": 80, "score": 7.012197971343994}, {"content": "Title: Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement Content: BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.", "qid": 11, "docid": "r9srhj4q", "rank": 81, "score": 7.012197017669678}, {"content": "Title: Addressing Coronavirus Disease 2019 in Spine Surgery: A Rapid National Consensus Using the Delphi Method via Teleconference Content: The magnitude and potential duration of the current coronavirus disease 2019 (COVID-19) pandemic is something that most doctors currently in practice have yet to experience. While considerable information regarding COVID-19 is being published every day, it is challenging to filter out the most relevant or appropriate information for our individual practice. The Spine Society of Singapore convened via a teleconference on April 24, 2020 to collaborate on a national level and share collective wisdom in order to tackle the ongoing crisis. In the teleconference, 13 spine surgeons from across various hospitals in Singapore constituted the panel of experts. The following topics were discussed: repurposing of surgeons, continuity of spine services, introduction of telemedicine, triaging of spinal surgeries, preoperative testing, new challenges in performing spine surgery, and preparing for the post-pandemic era. While some issues required only the sharing of best practices, the Delphi panel method was adopted to form a consensus on others. Existing spine specific triage guidelines were debated and a locally accepted set of guidelines was established. Although preoperative testing is currently not performed routinely, the panel voted in favor of its implementation because they concluded that it is vital to protect themselves, their colleagues, and their patients. Solutions to operating room specific concerns were also discussed. This article reflects the opinions and insights shared during this meeting and reviews the evidence relevant to the issues that were raised. The rapid consensus reached during the teleconference has enabled us to be concerted, and thus stronger, in our national efforts to provide the best standard of care via our spine services in these challenging times. We believe that this article will provide some guidance for addressing COVID-19 in spine surgery and encourage other national/regional societies to conduct similar discussions that would help their navigation of this pandemic.", "qid": 11, "docid": "zsv0tt1l", "rank": 82, "score": 7.0005998611450195}, {"content": "Title: Anticoagulation Options for Coronavirus Disease 2019 (COVID-19)-Induced Coagulopathy Content: As the coronavirus disease 2019 (COVID-19) pandemic is evolving, coagulopathy induced by the disease and its severe complications are raising concerns in the medical community. Because coagulopathy caused by COVID-19 has been difficult to control, it is important to have a better understanding of what therapies have been studied thus far and what therapies have demonstrated better outcomes for hospitalized patients. This review is focused on literature, research, and expert clinical judgments published in 2020 with a few references to articles published earlier. The review introduces the interim guidelines of the International Society of Thrombosis and Haemostasis (ISTH) for management of COVID-19-induced coagulopathy, discusses the efficacy of these guidelines in clinical settings, and summarizes the response of the scientific community to these guidelines and their clinical implications. Due to the failure of patients to respond to the prophylactic doses of heparin recommended by ISTH, higher doses of heparin may be necessary to achieve adequate anticoagulation. Patients\u2019 resistance to prophylactic doses of heparin could be due to low levels of anti-thrombin and high levels of fibrinogen, which would reinforce the use of therapeutic doses of heparin in the early stages of hospitalization. The review also compares low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as anticoagulant choices for COVID-19 patients. Given the complications specific to COVID-19, UFH may be a better choice of anticoagulant. Outpatient anticoagulation options are also reviewed. Changing qualified patients from vitamin K antagonists (VKA) to direct-acting oral anticoagulant (DOAC) for the convenience of less frequent monitoring may be appropriate. New anticoagulant, nafamostat, used in Japan is also discussed as a possible potentiate for heparin therapy.", "qid": 11, "docid": "dip71w25", "rank": 83, "score": 6.984499931335449}, {"content": "Title: Triaging patients in the outbreak of the 2019 novel coronavirus Content: In the end of 2019, the epidemic of a new coronavirus (SARS-CoV-2) occurred in Wuhan and spread rapidly. Changsha, a city located south to the epicenter, was soon impacted. To control the transmission of the coronavirus and avoid nosocomial infection, triage procedures based on epidemiology were implemented in a local hospital of the city. This retrospective study analyzed the data collected during the triage period and found that COVID-19 patients were enriched seven folds into the Section A designated for rapid detection and quarantine. On the other side, roughly triple amounts of visits were received at the Section B for patients without obvious epidemiological history. Eight COVID-19 cases were spotted out of 247 suspected patients. More than 50% of the suspected patients were submitted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection. Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as a COVID-19 case. Of the eight COVID-19 patients, three were confirmed only after multiple rounds of nucleic acid analysis. Besides comorbidities, delayed sharing of epidemiological history added another layer of complexity to the diagnosis in practice. While SARS-CoV-2 epidemic is being alerted in many countries, our report will be helpful to other colleagues in rapid identification of COVID-19 cases and controlling the transmission of the disease.", "qid": 11, "docid": "tof0so67", "rank": 84, "score": 6.979499816894531}, {"content": "Title: Infection control practices in children during COVID-19 pandemic: Differences from adults Content: BACKGROUND: Limited studies have been published on practices and management of Coronavirus Disease 2019 (COVID-19) in children. Despite the fact that COVID-19 rarely caused any severe disease in children, the asymptomatic children might be playing an important role for spreading COVID-19 in healthcare facilities. This review aimed at sharing our experience of how to handle patients with COVID-19 in a pediatric referral and tertiary care hospital to prevent the possible transmissions to the healthcare workers (HCWs). METHODS: This review sought to identify infection control practices measures during COVID-19 pandemic comes from our daily practice combined with the most recent guidelines with the new experience and information. RESULTS: Prevention the transmission of COVID-19 to the HCWs, 4 primary themes should be taken into consideration; (1) ongoing education and importance of the organization of the healthcare facility, (2) proper clinical triage and isolation of the suspected or confirmed COVID-19 patients in the outpatient clinics and in the emergency departments, (3) necessity of the organization of the COVID-19 wards, and (4) utilization of personal protective equipment. CONCLUSIONS: Infection control precautions to prevent the possible transmissions to HCWs as well as the other patients and their caregivers from children with COVID-19 are very critical. If sufficient precautions are not taken, healthcare settings may serve as additional source of transmission and spread of COVID-19 in the society.", "qid": 11, "docid": "q1zyesvx", "rank": 85, "score": 6.9710001945495605}, {"content": "Title: Neurological Impact of Coronavirus Disease of 2019: Practical Considerations for the Neuroscience Community Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020, with more than 187,000 deaths. An increasing body of evidence has supported central nervous system involvement. METHODS: We conducted a review of the reported data for studies concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. RESULTS: Central nervous system manifestations range from vague nonfocal complaints to severe neurological impairment associated with encephalitis. It is unclear whether the neurological dysfunction results from direct viral injury or systemic disease. The virus could affect brainstem pathways that lead to indirect respiratory dysfunction, in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of the ongoing scientific and clinical findings. CONCLUSIONS: The present review has consolidated the current body of data regarding the neurological impact of coronaviruses, discussed the reported neurological manifestations of COVID-19, and highlighted the recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons have also been provided.", "qid": 11, "docid": "idxxu82o", "rank": 86, "score": 6.962500095367432}, {"content": "Title: Asymptomatic carriage and transmission of SARS-CoV-2: What do we know? Content: PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.", "qid": 11, "docid": "f76ypfma", "rank": 87, "score": 6.929599761962891}, {"content": "Title: COVID-19: Preliminary Clinical Guidelines for Ophthalmology Practices Content: The zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant human coronavirus disease (COVID-19) recently appeared as a global health threat that can cause severe respiratory infection and terminal respiratory distress. By the first week of April, more than 1.3 million people had been globally infected and more than 70,000 had lost their lives to this contagious virus. Clinical manifestations occur shortly after exposure, or a few days later. There is controversy regarding the transmission of the virus through the tear and conjunctiva; however, there are reports that the ocular surface might be a potential target for COVID-19. The ease of transmission of this virus at close proximity presents a risk to eyecare workers. Several recommendations have been issued by local and national organizations to address the issue of safe ophthalmic practice during the ongoing COVID-19 pandemic. These guidelines have numerous similarities; however, subtle differences exist. The purpose of this paper was to discuss measures, with a specific focus on standard precautions, to prevent further dissemination of COVID-19 at Eye Clinics. We have proposed procedures to triage suspected cases of COVID-19, considering emergency conditions.", "qid": 11, "docid": "2qqkoeo9", "rank": 88, "score": 6.901100158691406}, {"content": "Title: COVID-19: Preliminary Clinical Guidelines for Ophthalmology Practices Content: The zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant human coronavirus disease (COVID-19) recently appeared as a global health threat that can cause severe respiratory infection and terminal respiratory distress By the first week of April, more than 1 3 million people had been globally infected and more than 70,000 had lost their lives to this contagious virus Clinical manifestations occur shortly after exposure, or a few days later There is controversy regarding the transmission of the virus through the tear and conjunctiva;however, there are reports that the ocular surface might be a potential target for COVID-19 The ease of transmission of this virus at close proximity presents a risk to eyecare workers Several recommendations have been issued by local and national organizations to address the issue of safe ophthalmic practice during the ongoing COVID-19 pandemic These guidelines have numerous similarities;however, subtle differences exist The purpose of this paper was to discuss measures, with a specific focus on standard precautions, to prevent further dissemination of COVID-19 at Eye Clinics We have proposed procedures to triage suspected cases of COVID-19, considering emergency conditions", "qid": 11, "docid": "5l308s0c", "rank": 89, "score": 6.90109920501709}, {"content": "Title: COVID-19: Preliminary Clinical Guidelines for Ophthalmology Practices. Content: The zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant human coronavirus disease (COVID-19) recently appeared as a global health threat that can cause severe respiratory infection and terminal respiratory distress. By the first week of April, more than 1.3 million people had been globally infected and more than 70,000 had lost their lives to this contagious virus. Clinical manifestations occur shortly after exposure, or a few days later. There is controversy regarding the transmission of the virus through the tear and conjunctiva; however, there are reports that the ocular surface might be a potential target for COVID-19. The ease of transmission of this virus at close proximity presents a risk to eyecare workers. Several recommendations have been issued by local and national organizations to address the issue of safe ophthalmic practice during the ongoing COVID-19 pandemic. These guidelines have numerous similarities; however, subtle differences exist. The purpose of this paper was to discuss measures, with a specific focus on standard precautions, to prevent further dissemination of COVID-19 at Eye Clinics. We have proposed procedures to triage suspected cases of COVID-19, considering emergency conditions.", "qid": 11, "docid": "8jhubc2q", "rank": 90, "score": 6.901098251342773}, {"content": "Title: Evaluation of visual triage for screening of Middle East respiratory syndrome coronavirus patients Content: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 in Saudi Arabia had attracted the attention of the global health community. In 2017 the Saudi Ministry of Health released a visual triage system with scoring to alert healthcare workers in emergency departments (EDs) and haemodialysis units for the possibility of occurrence of MERS-CoV infection. We performed a retrospective analysis of this visual score to determine its sensitivity and specificity. The study included all cases from 2014 to 2017 in a MERS-CoV referral centre in Riyadh, Saudi Arabia. During the study period there were a total of 2435 suspected MERS cases. Of these, 1823 (75%) tested negative and the remaining 25% tested positive for MERS-CoV by PCR assay. The application of the visual triage score found a similar percentage of MERS-CoV and non\u2013MERS-CoV patients, with each score from 0 to 11. The percentage of patients with a cutoff score of \u22654 was 75% in patients with MERS-CoV infection and 85% in patients without MERS-CoV infection (p 0.0001). The sensitivity and specificity of this cutoff score for MERS-CoV infection were 74.1% and 18.6%, respectively. The sensitivity and specificity of the scoring system were low, and further refinement of the score is needed for better prediction of MERS-CoV infection.", "qid": 11, "docid": "4hk736ev", "rank": 91, "score": 6.900100231170654}, {"content": "Title: The good, the bad and the ugly: pandemic priority decisions and triage Content: In this analysis we discuss the change in criteria for triage of patients during three different phases of a pandemic like COVID-19, seen from the critical care point of view. Availability of critical care beds has become a hot topic, and in many countries, we have seen a huge increase in the provision of temporary intensive care bed capacity. However, there is a limit where the hospitals may run out of resources to provide critical care, which is heavily dependent on trained staff, just-in-time supply chains for clinical consumables and drugs and advanced equipment. In the first (good) phase, we can still do clinical prioritisation and decision-making as usual, based on the need for intensive care and prognostication: what are the odds for a good result with regard to survival and quality of life. In the next (bad phase), the resources are mostly available, but the system is stressed by many patients arriving over a short time period and auxiliary beds in different places in the hospital being used. We may have to abandon admittance of patients with doubtful prognosis. In the last (ugly) phase, usual medical triage and priority setting may not be sufficient to decrease inflow and there may not be enough intensive care unit beds available. In this phase different criteria must be applied using a utilitarian approach for triage. We argue that this is an important transition where society, and not physicians, must provide guidance to support triage that is no longer based on medical priorities alone.", "qid": 11, "docid": "dvmv5u5j", "rank": 92, "score": 6.870999813079834}, {"content": "Title: How can dentistry get back to work safely? Content: Data sources Narrative review Study abstract This review provides a synopsis of our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease, COVID-19. The virus is shed in the nasopharyngeal and salivary secretions of carriers, and this puts dental professionals at risk for increased exposure of SARS-CoV-2. The paper summarises the current guidelines outlined by the CDC and presents the triaging protocols to identify potential carriers and how to safely limit treatment to low-risk patients.", "qid": 11, "docid": "6p6v6z9q", "rank": 93, "score": 6.866499900817871}, {"content": "Title: How can dentistry get back to work safely? Content: Data sources Narrative reviewStudy abstract This review provides a synopsis of our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease, COVID-19. The virus is shed in the nasopharyngeal and salivary secretions of carriers, and this puts dental professionals at risk for increased exposure of SARS-CoV-2. The paper summarises the current guidelines outlined by the CDC and presents the triaging protocols to identify potential carriers and how to safely limit treatment to low-risk patients.", "qid": 11, "docid": "cu2f91rf", "rank": 94, "score": 6.866498947143555}, {"content": "Title: Will the guidelines and recommendations for surgery during COVID-19 pandemic still be valid if it becomes endemic? Content: The current COVID-19 pandemic has impacted all the healthcare sectors all over the world. The WHO and various other health organizations have been issuing recommendations and guidelines for surgical practice and patient management during the current pandemic. Some of these guidelines include triaging of the patients, prioritizing emergency surgery and delaying the elective surgical procedures till the COVID-19 pandemic is over. However, it seems that COVID-19 might become endemic in the community and current guidelines might not hold true. Surgical practices cannot remain suspended forever as it will have a deleterious effect on surgeons and patients. Therefore we need novel guidelines so that the surgeons can resume their general surgical practice as soon as possible.", "qid": 11, "docid": "7b72491d", "rank": 95, "score": 6.858399868011475}, {"content": "Title: Will the Guidelines and Recommendations for Surgery During COVID-19 Pandemic still be valid if it Becomes Endemic? Content: The current COVID-19 pandemic has impacted all the healthcare sectors all over the world. The WHO and various other health organizations have been issuing recommendations and guidelines for surgical practice and patient management during the current pandemic. Some of these guidelines include triaging of the patients, prioritizing emergency surgery and delaying the elective surgical procedures till the COVID-19 pandemic is over. However, it seems that COVID-19 might become endemic in the community and current guidelines might not hold true. Surgical practices cannot remain suspended forever as it will have a deleterious effect on surgeons and patients. Therefore we need novel guidelines so that the surgeons can resume their general surgical practice as soon as possible.", "qid": 11, "docid": "ndngpmpw", "rank": 96, "score": 6.858398914337158}, {"content": "Title: Patients asymptomatiques du SARS-CoV-2 et transmission du virus : O\u00f9 en sont nos connaissances?/ Asymptomatic carriage and transmission of SARS-CoV-2: What do we know? Content: PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.", "qid": 11, "docid": "7h7v6abe", "rank": 97, "score": 6.843100070953369}, {"content": "Title: Patient-Led COVID-19 Triage Systems and Case Fatality Rates: A Comparative Study Between Singapore, Japan, Norway, the USA and the UK. Content: Introduction: The case fatality rate from COVID-19 differs markedly around the world. There are likely a number of factors one can attribute to such disparity, not least of which is differing healthcare models and approaches. Here, we examine the COVID-19 related health advice issued by six different countries, specifically examining the patient-led triage pathways in each country. Methods: A simulation study was conducted on current, nationwide, patient-led triage systems from three countries with low case fatality rates (Singapore, Norway and Japan) and two countries with high case fatality rates (the USA and the UK). 36 case scenarios were designed to imitate common presentations of COVID-19 with varying degrees of severity. These scenarios were then fed into each countrys patient-led triage system. The advice for each scenario was recorded and then compared. Results: Patient-led triage systems from Singapore, Japan and Norway maintained a low threshold for advising clinical contact for patients with possible COVID-19 (88 to 100% of cases were referred). Patient-led triage systems from the USA and the UK maintained high thresholds for advising contact with either call centre support or clinical contact (28 and 33% of cases were referred, respectively), and triaged the majority of cases home with no further healthcare input. There was a strong inverse correlation between percentage of cases referred and the nations case fatality rate (Pearsons Correlation = -0.642, p = 0.01). Conclusion: In this simulation study, countries with low case fatality rates - Singapore, Norway and Japan -, performed well, successfully identifying severe COVID-19 and triaging such cases to medical care. The USA triage system (CDCs Coronavirus Self-Checker) and the UKs triage system (NHS 111 online) performed poorly, failing to identify Severe COVID-19 infection and sepsis in the case simulations, and triaging the majority of cases to self-care with no further healthcare input. Such poorly performing triage systems are likely to be contributing to the high case fatality rates in the US and the UK.", "qid": 11, "docid": "6xer2cty", "rank": 98, "score": 6.840700149536133}, {"content": "Title: Key Strategies for Clinical Management and Improvement of Healthcare Services for Cardiovascular Disease and Diabetes Patients in the Coronavirus (COVID-19) Settings: Recommendations From the REPROGRAM Consortium Content: Patients with cardiovascular disease and diabetes are at potentially higher risk of infection and fatality due to COVID-19. Given the social and economic costs associated with disability due to these conditions, it is imperative that specific considerations for clinical management of these patients be observed. Moreover, the reorganization of health services around the pandemic response further exacerbates the growing crisis around limited access, treatment compliance, acute medical needs, and mental health of patients in this specific subgroup. Existing recommendations and guidelines emanating from respective bodies have addressed some of the pressure points; however, there are variations and limitations vis a vis patient with multiple comorbidities such as obesity. This article will pull together a comprehensive assessment of the association of cardiovascular disease, diabetes, obesity and COVID-19, its impact on the health systems and how best health systems can respond to mitigate current challenges and future needs. We anticipate that in the context of this pandemic, the cardiovascular disease and diabetes patients need a targeted strategy to ensure the harm to this group does not translate to huge costs to society and to the economy. Finally, we propose a triage and management protocol for patients with cardiovascular disease and diabetes in the COVID-19 settings to minimize harm to patients, health systems and healthcare workers alike.", "qid": 11, "docid": "iu2rgpb0", "rank": 99, "score": 6.829999923706055}, {"content": "Title: To Do or Not to Do?-A Review of Cancer Surgery Triage Guidelines in COVID-19 Pandemic Content: COVID-19 pandemic has emerged as a global health emergency involving more than 200 countries so far. The number of affected population is on rising, so is the mortality. This crisis has overwhelmed the healthcare infrastructures in many affected countries. Due to overall rising cancer incidence and specific concerns, a cohort of cancer patients forms a distinct subset of the population in whom a correct and timely treatment has a huge impact on the outcome. During this period, oncology care is definitely affected owing to many factors like lockdowns, reduced beds and deferral of elective cases to halt the spread of the pandemic. Surgery remains the best line of defence in many solid organ tumours especially in early stage and is potentially curative. China, the source of this pandemic, has taken more than 3 months to enter the post transitional phase of this pandemic. Deferring cancer surgeries for this long period may have a direct impact on the long-term outcomes of cancer patients. Many surgical oncology associations across the globe have come up with triage guidelines for surgical care of cancer patients; however, these are based on expert opinion rather than actual data. Herein, we intend to review these guidelines with respect to the risk of disease progression in cancer patients. In the absence of actual data on cancer surgery care during this pandemic, clinical decisions should be based on careful consideration of disease-related and patient-related factors. While some of the cancer surgeries can be safely delayed for some time, how long we can delay surgeries safely cannot be answered/ explained by any means. Thorough evaluation and discussion by an expert and experienced multidisciplinary team appears to be the most effective way forward.", "qid": 11, "docid": "1ogglaa3", "rank": 100, "score": 6.824100017547607}]}
{"query": "what are best practices in hospitals and at home in maintaining quarantine?", "hits": [{"content": "Title: Functional assessment and function-based treatment delivered via telehealth: A brief summary Content: As the world navigates the COVID-19 health crisis, behavior analysts are considering how best to support families while maintaining services and ensuring the health and safety of everyone involved. Telehealth is one service delivery option that provides families with access to care in their own communities and homes. In this article, we provide a brief summary of the telehealth literature in applied behavior analysis that provided coaching and training to families for individuals who displayed challenging behavior. These studies targeted functional assessment and function-based treatment for challenging behavior. We briefly summarize what is known relative to the assessment and treatment of challenging behavior via telehealth, place these results within a descriptive context of the decisions made by the research team at the University of Iowa, and discuss what we, as behavior analysts, should consider next to advance our understanding and practice of telehealth.", "qid": 12, "docid": "rb416bbs", "rank": 1, "score": 10.191699981689453}, {"content": "Title: Functional assessment and function\u2010based treatment delivered via telehealth: A brief summary Content: As the world navigates the COVID\u201019 health crisis, behavior analysts are considering how best to support families while maintaining services and ensuring the health and safety of everyone involved. Telehealth is one service delivery option that provides families with access to care in their own communities and homes. In this article, we provide a brief summary of the telehealth literature in applied behavior analysis that provided coaching and training to families for individuals who displayed challenging behavior. These studies targeted functional assessment and function\u2010based treatment for challenging behavior. We briefly summarize what is known relative to the assessment and treatment of challenging behavior via telehealth, place these results within a descriptive context of the decisions made by the research team at the University of Iowa, and discuss what we, as behavior analysts, should consider next to advance our understanding and practice of telehealth.", "qid": 12, "docid": "x70u9gz6", "rank": 2, "score": 10.191699028015137}, {"content": "Title: 2018 AAHA Infection Control, Prevention, and Biosecurity Guidelines. Content: A veterinary team's best work can be undone by a breach in infection control, prevention, and biosecurity (ICPB). Such a breach, in the practice or home-care setting, can lead to medical, social, and financial impacts on patients, clients, and staff, as well as damage the reputation of the hospital. To mitigate these negative outcomes, the AAHA ICPB Guidelines Task Force believes that hospital teams should improve upon their current efforts by limiting pathogen exposure from entering or being transmitted throughout the hospital population and using surveillance methods to detect any new entry of a pathogen into the practice. To support these recommendations, these practice-oriented guidelines include step-by-step instructions to upgrade ICPB efforts in any hospital, including recommendations on the following: establishing an infection control practitioner to coordinate and implement the ICPB program; developing evidence-based standard operating procedures related to tasks performed frequently by the veterinary team (hand hygiene, cleaning and disinfection, phone triage, etc.); assessing the facility's ICPB strengths and areas of improvement; creating a staff education and training plan; cataloging client education material specific for use in the practice; implementing a surveillance program; and maintaining a compliance evaluation program. Practices with few or no ICPB protocols should be encouraged to take small steps. Creating visible evidence that these protocols are consistently implemented within the hospital will invariably strengthen the loyalties of clients to the hospital as well as deepen the pride the staff have in their roles, both of which are the basis of successful veterinary practice.", "qid": 12, "docid": "8z3l5k4l", "rank": 3, "score": 9.829099655151367}, {"content": "Title: Impact of Home Quarantine on Physical Activity Among Older Adults Living at Home During the COVID-19 Pandemic: Qualitative Interview Study Content: BACKGROUND: Older adults and those with pre-existing medical conditions are at risk of death from severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). In this period of quarantine, one of the reasons for going out is physical activity. This issue is important, as the impact of a sedentary lifestyle might be lower for children and young adults, but is far more severe for older adults. Although older adults need to stay at home because they have a higher risk of coronavirus disease (COVID-19), they need to avoid a sedentary lifestyle. Physical activity is important for older adults, especially to maintain their level of independence, mental health, and well-being. Maintaining mobility in old age is necessary, as it may predict loss of independence in older adults. OBJECTIVE: Our first objective was to evaluate the impact of this quarantine period on physical activity programs and on the physical and mental health of older adults. Our second objective was to discuss alternatives to physical activity programs that could be suggested for this population to avoid a sedentary lifestyle. METHODS: We conducted a qualitative survey using semistructured interviews with professionals (managers in charge of physical activity programs for older adults and sports trainers who run these physical activity programs) from the French Federation of Physical Education and Voluntary Gymnastics (FFPEVG) and older adults participating in a physical activity program of the FFPEVG. We followed a common interview guide. For analysis, we carried out a thematic analysis of the interviews. RESULTS: This study suggests that the COVID-19 epidemic has affected, before quarantine measures, the number of seniors attending group physical activity programs in the two study territories. In addition, despite the decline in their participation in group physical activities before the quarantine, older adults expressed the need to perform physical activity at home. There is a need to help older adults integrate simple and safe ways to stay physically active in a limited space. A national policy to support older adults for physical activity at home appears essential in this context. CONCLUSIONS: Given the results of our study, it seems necessary to globally communicate how important it is for older adults to maintain physical activity at home. We are concerned about the level of independence and mental health state of older adults after the end of quarantine if there is no appropriate campaign to promote physical activity among them at home.", "qid": 12, "docid": "0ojan1ey", "rank": 4, "score": 9.300600051879883}, {"content": "Title: Understanding the current status of patients with pulmonary hypertension during COVID-19 outbreak: a small-scale national survey from China Content: Pulmonary hypertension is a chronic disease developing progressively with high mortality. Pulmonary hypertension patients need persistent medical care; however, limited reports focused on them when there was an outbreak of coronavirus disease 2019 in China. This national survey was aimed to evaluate the overall condition of pulmonary hypertension patients during this period. A questionnaire regarding the living condition of pulmonary hypertension patients during coronavirus disease 2019 was designed by pulmonary hypertension diagnostic experts in Wuhan Asia Heart Hospital. Pulmonary hypertension patients and their family members were invited to participate in this survey online. One-hundred twenty pulmonary hypertension patients and 23 family members participated in the survey; 64.8% (n = 87) participants came from Hubei, and others were from 15 other provinces; 98.6% (n = 141) participants were in home quarantine; 65.8% (n = 79) were pulmonary arterial hypertension associated with congenital heart disease; and 76.7% (n = 92) patients proclaimed their heart function was well maintained at class I or II. One (0.8%) patient was confirmed severe acute respiratory syndrome coronavirus 2 infection. Two (1.7%) patients were hospitalized due to heart function worsening. Nearly 70% (n = 100) participants implied shortage in medications during coronavirus disease 2019 outbreak. A total of 24.2% (n = 29) patients indicated that medications were discontinued due to the insufficient supply. Most of the participants stayed optimistic on either coronavirus disease 2019 outbreak or their pulmonary hypertension disease, and 61.7% (n = 74) patients would go to the hospital for follow-up immediately after outbreak. These preliminary data show pulmonary hypertension patients are able to avoid severe disease when they are in home quarantine. Medication supplement is important for pulmonary hypertension patients when their heart function is well maintained. In addition, there might be increasing requirements of medical care for pulmonary hypertension patients after the outbreak.", "qid": 12, "docid": "1nxfh9yt", "rank": 5, "score": 8.928799629211426}, {"content": "Title: A home hospitalization system based on the Internet of things, Fog computing and cloud computing Content: In recent years, the world has witnessed a significant increase in the number of elderly who often suffer from chronic diseases, and has witnessed in recent months a major spread of the new coronavirus (COVID-19), which has led to thousands of deaths, especially among the elderly and people who suffer from chronic diseases. Coronavirus has also caused many problems in hospitals, where these are no longer able to accommodate a large number of patients. This virus has also begun to spread between medical and paramedical teams, and this causes a major risk to the health of patients staying in hospitals. To reduce the spread of the virus and maintain the health of patients who need a hospital stay, home hospitalization is one of the best possible solutions. This paper proposes a home hospitalization system based on the Internet of Things (IoT), Fog computing, and Cloud computing, which are among the most important technologies that have contributed to the development of the healthcare sector in a significant way. These systems allow patients to recover and receive treatment in their homes and among their families, where patient health and the hospitalization room environmental state are monitored, to enable doctors to follow the hospitalization process and make recommendations to patients and their supervisors, through monitoring units and mobile applications developed for this purpose. The results of evaluation have shown great acceptance of this system by patients and doctors alike.", "qid": 12, "docid": "azgfda21", "rank": 6, "score": 8.831100463867188}, {"content": "Title: FORECASTING COVID-19 PANDEMIC: A DATA-DRIVEN ANALYSIS Content: In this paper, a new Susceptible-Exposed-Symptomatic Infectious-Asymptomatic Infectious-Quarantined-Hospitalized-Recovered-Dead (SEIDIUQHRD) deterministic compartmental model has been proposed and calibrated for describing the transmission dynamics of the novel coronavirus disease (COVID-19). A calibration process is executed through the solution of an inverse problem with the help of a Trust-Region-Reflective algorithm, used to determine the best parameter values that would fit the model response. The purpose of this study is to give a tentative prediction of the epidemic peak for Russia, Brazil, India and Bangladesh which could become the next COVID-19 hotspots in no time. Based on the publicly available epidemiological data from late January until 10 May, it has been estimated that the number of daily new symptomatic infectious cases for the above mentioned countries could reach the peak around the beginning of June with the peak size of {approx}15,774 symptomatic infectious cases in Russia, {approx}26,449 cases in Brazil, {approx}9,504 cases in India and {approx}2,209 cases in Bangladesh. Based on our analysis, the estimated value of the basic reproduction number (R0) as of May 11, 2020 was found to be {approx}4.234 in Russia, {approx}5.347 in Brazil, {approx}5.218 in India, {approx}4.649 in the United Kingdom and {approx}3.5 in Bangladesh. Moreover, with an aim to quantify the uncertainty of our model parameters, Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) which is a global sensitivity analysis (GSA) method is applied which elucidates that, for Russia, the recovery rate of undetected asymptomatic carriers, the rate of getting home-quarantined or self-quarantined and the transition rate from quarantined class to susceptible class are the most influential parameters, whereas the rate of getting home-quarantined or self-quarantined and the inverse of the COVID-19 incubation period are highly sensitive parameters in Brazil, India, Bangladesh and the United Kingdom which could significantly affect the transmission dynamics of the novel coronavirus. Our analysis also suggests that relaxing social distancing restrictions too quickly could exacerbate the epidemic outbreak in the above mentioned countries.", "qid": 12, "docid": "cgde85eo", "rank": 7, "score": 8.62090015411377}, {"content": "Title: epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England Content: Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were originally commissioned by the Department of Health and developed during 1998\u20132000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were first published in January 2001 1 and updated in 2007. 2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective for the prevention of HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. The Department of Health commissioned a review of new evidence and we have updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the epic2 guidelines published in 2007 remain robust, relevant and appropriate, but some guideline recommendations required adjustments to enhance clarity and a number of new recommendations were required. These have been clearly identified in the text. In addition, the synopses of evidence underpinning the guideline recommendations have been updated. These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence. National evidence-based guidelines are broad principles of best practice that need to be integrated into local practice guidelines and audited to reduce variation in practice and maintain patient safety. Clinically effective infection prevention and control practice is an essential feature of patient protection. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of health care in NHS hospitals in England can be minimised.", "qid": 12, "docid": "nb0j6k3h", "rank": 8, "score": 8.611700057983398}, {"content": "Title: Best Practices for Healthcare Facility and Regional Stockpile Maintenance and Sustainment: A Literature Review. Content: Preparing for mass casualty incidents is essential to maximizing community resilience. Many US-based organizations and regions have developed stockpiles of medications, supplies, and equipment for mass casualty incident preparedness. The Centers for Disease Control and Prevention (CDC) assess and manage federally stockpiled materials, but hospitals, healthcare systems, and regional organizations are responsible for maintaining locally owned caches. The CDC has protocols for assessing and managing the Strategic National Stockpile, but no such guidance exists for local or geographical/regional stockpiles. This article outlines best practices and recommendations identified in the literature related to maintaining and sustaining a local or regional stockpile. Recommendations are provided on the timing and procedures for assessing, inventorying, storing, managing, tracking, and deploying materials stockpiled on site, in a trailer, or in a warehouse. In addition, alternative approaches for maintaining a local or regional cache, such as vendor- or user-managed inventory methods, are addressed. Management of local or regional caches requires an investment in infrastructure and training but is necessary to ensure the integrity of stockpiled medication and supplies and to enable rapid and appropriate activation during a mass casualty incident. Hospitals, healthcare systems, businesses, academic institutions, public health agencies, organizations, and regions can use the recommendations here to develop protocols or policies to properly manage their existing stockpiles, which should minimize costs related to damaged supplies.", "qid": 12, "docid": "e4sshkgk", "rank": 9, "score": 8.591699600219727}, {"content": "Title: Dealing with sleep problems during home confinement due to the COVID-19 outbreak: Practical recommendations from a task force of the European CBT-I Academy Content: In the current global home confinement situation due to the COVID-19 outbreak, most individuals are exposed to an unprecedented stressful situation of unknown duration. This may not only increase daytime stress, anxiety and depression levels, but also disrupt sleep. Importantly, because of the fundamental role that sleep plays in emotion regulation, sleep disturbance can have direct consequences upon next day emotional functioning. In this paper, we summarize what is known about the stress-sleep link and confinement as well as effective insomnia treatment. We discuss those effects of the current home confinement situation that can disrupt sleep but also those that could benefit sleep quality. We suggest adaptions of cognitive behavioural therapy elements that are feasible to implement for those facing changed work schedules and requirements, those with health anxiety and those handling childcare and home-schooling, whilst also recognizing the general limitations imposed on physical exercise and social interaction. Managing sleep problems as best as possible during home confinement can limit stress and possibly prevent disruptions of social relationships.", "qid": 12, "docid": "lf6t8xmm", "rank": 10, "score": 8.455300331115723}, {"content": "Title: Home Birth in the Era of COVID-19: Counseling and Preparation for Pregnant Persons Living with HIV Content: With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted \"shelter-in-place\" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: \u00b7 Coronavirus disease 2019 pandemic has increased interest in home birth.. \u00b7 Women living with HIV are pursuing home birth.. \u00b7 Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..", "qid": 12, "docid": "as5d3hk4", "rank": 11, "score": 8.407600402832031}, {"content": "Title: Home Birth in the Era of COVID-19: Counseling and Preparation for Pregnant Persons Living with HIV. Content: With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted \"shelter-in-place\" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: \u00b7 Coronavirus disease 2019 pandemic has increased interest in home birth.. \u00b7 Women living with HIV are pursuing home birth.. \u00b7 Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..", "qid": 12, "docid": "wyuz1az9", "rank": 12, "score": 8.407599449157715}, {"content": "Title: How long does Coronavirus survive on different surfaces? Content: Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices", "qid": 12, "docid": "7ftq02ev", "rank": 13, "score": 8.389900207519531}, {"content": "Title: Monitoring and Management of Home-Quarantined Patients With COVID-19 Using a WeChat-Based Telemedicine System: Retrospective Cohort Study Content: BACKGROUND: Most patients with coronavirus disease (COVID-19) who show mild symptoms are sent home by physicians to recover. However, the condition of some of these patients becomes severe or critical as the disease progresses. OBJECTIVE: The aim of this study was to evaluate a telemedicine model that was developed to address the challenges of treating patients with progressive COVID-19 who are home-quarantined and shortages in the medical workforce. METHODS: A telemedicine system was developed to continuously monitor the progression of home-quarantined patients with COVID-19. The system was built based on a popular social media smartphone app called WeChat; the app was used to establish two-way communication between a multidisciplinary team consisting of 7 medical workers and 188 home-quarantined individuals (including 74 confirmed patients with COVID-19). The system helped patients self-assess their conditions and update the multidisciplinary team through a telemedicine form stored on a cloud service, based on which the multidisciplinary team made treatment decisions. We evaluated this telemedicine system via a single-center retrospective study conducted at Tongji Hospital in Wuhan, China, in January 2020. RESULTS: Among 188 individuals using the telemedicine system, 114 (60.6%) were not infected with COVID-19 and were dismissed. Of the 74 confirmed patients with COVID-19, 26 (35%) recovered during the study period and voluntarily stopped using the system. The remaining 48/76 confirmed patients with COVID-19 (63%) used the system until the end of the study, including 6 patients whose conditions progressed to severe or critical. These 6 patients were admitted to hospital and were stabilized (one received extracorporeal membrane oxygenation support for 17 days). All 74 patients with COVID-19 eventually recovered. Through a comparison of the monitored symptoms between hospitalized and nonhospitalized patients, we found prolonged persistence and deterioration of fever, dyspnea, lack of strength, and muscle soreness to be diagnostic of need for hospitalization. CONCLUSIONS: By continuously monitoring the changes in several key symptoms, the telemedicine system reduces the risks of delayed hospitalization due to disease progression for patients with COVID-19 quarantined at home. The system uses a set of scales for quarantine management assessment that enables patients to self-assess their conditions. The results are useful for medical staff to identify disease progression and, hence, make appropriate and timely treatment decisions. The system requires few staff to manage a large cohort of patients. In addition, the system can solicit help from recovered but self-quarantined medical workers to alleviate shortages in the medical workforce and free healthy medical workers to fight COVID-19 on the front line. Thus, it optimizes the usage of local medical resources and prevents cross-infections among medical workers and patients.", "qid": 12, "docid": "k6qbxrg6", "rank": 14, "score": 8.38949966430664}, {"content": "Title: Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy. Content: In the current global home confinement situation due to the COVID-19 outbreak, most individuals are exposed to an unprecedented stressful situation of unknown duration. This may not only increase daytime stress, anxiety and depression levels but also disrupt sleep. Importantly, because of the fundamental role that sleep plays in emotion regulation, sleep disturbance can have direct consequences upon next day emotional functioning. In this paper we summarize what is known about the stress-sleep link and confinement as well as effective insomnia treatment. We discuss those effects of the current home confinement situation that can disrupt sleep but also those that could benefit sleep quality. We suggest adaptions of cognitive behavioral therapy elements that are feasible to implement for those facing changed work schedules and requirements, those with health anxiety and those handling childcare and homeschooling, whilst also recognizing the general limitations imposed on physical exercise and social interaction. Managing sleep problems as best as possible during home confinement can limit stress and possibly prevent disruptions of social relationships.", "qid": 12, "docid": "x1ffjbvi", "rank": 15, "score": 8.326399803161621}, {"content": "Title: Methicillin-resistant Staphylococcus aureus, Clostridium difficile, and extended-spectrum \u03b2-lactamase\u2013producing Escherichia coli in the community: Assessing the problem and controlling the spread Content: Although health care-associated methicillin resistant staphylococcus aureus and clostridium difficile strains are primarily a risk to hospital patients, people are increasingly concerned about their potential to circulate in the community and the home. They are thus looking for support in order to understand the extent of the risk, and guidance on how to deal with situations where preventing infection from these species becomes their responsibility. A further concern are the community-acquired MRSA and C. difficile strains, and other antibiotic resistant strains circulating in the community such as the Extended-spectrum \u03b2-lactamase (ESBL) Escherichia coli. In response to concerns about such organisms in the community, the International Scientific Forum on Home Hygiene has produced a report evaluating MRSA, C. difficile, and ESBL-producing E. coli from a community viewpoint. The report summarizes what is known about their prevalence in the community, their mode of transmission in the home, and the extent to which they represent a risk. It also includes \u201cadvice sheets\u201d giving practical guidance on what to do when there is a risk of infection transmission in the home.", "qid": 12, "docid": "kln3t3ru", "rank": 16, "score": 8.296899795532227}, {"content": "Title: Response to the COVID-19 Pandemic: Practical Guide to Rapidly Deploying Home Workstations to Guarantee Radiology Services During Quarantine, Social Distancing, and Stay Home Orders Content: OBJECTIVE. The purpose of this article is to share an experience in the rapid deployment of home workstations that illustrates a creative solution that transcended typical administrative barriers. CONCLUSION. In response to the global coronavirus disease (COVID-19) pandemic, radiology departments need to rapidly deploy home PACS workstations to facilitate physical distancing and to guarantee radiologic expertise despite possible home quarantining or stay home, work safe orders.", "qid": 12, "docid": "0vkuxggb", "rank": 17, "score": 8.261500358581543}, {"content": "Title: Response to the COVID-19 Pandemic: Practical Guide to Rapidly Deploying Home Workstations to Guarantee Radiology Services During Quarantine, Social Distancing, and Stay Home Orders. Content: OBJECTIVE. The purpose of this article is to share an experience in the rapid deployment of home workstations that illustrates a creative solution that transcended typical administrative barriers. CONCLUSION. In response to the global coronavirus disease (COVID-19) pandemic, radiology departments need to rapidly deploy home PACS workstations to facilitate physical distancing and to guarantee radiologic expertise despite possible home quarantining or stay home, work safe orders.", "qid": 12, "docid": "nlfr3lth", "rank": 18, "score": 8.261499404907227}, {"content": "Title: Achieving Safe, Effective, and Compassionate Quarantine or Isolation of Older Adults With Dementia in Nursing Homes Content: Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight, and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe, and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.", "qid": 12, "docid": "iphuh7wp", "rank": 19, "score": 8.235199928283691}, {"content": "Title: Achieving Safe, Effective and Compassionate Quarantine or Isolation of Older Adults with Dementia in Nursing Homes. Content: Abstract Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.", "qid": 12, "docid": "q03884i9", "rank": 20, "score": 8.235198974609375}, {"content": "Title: Negative impact of the COVID-19 pandemic on sleep quantitative parameters, quality, and circadian alignment: Implications for psychological well-being and emotional regulation Content: Background The COVID-19 pandemic has spread worldwide, affecting millions of people and exposing them to home quarantine, isolation, and social distancing. While recent reports showed increased distress and depressive/anxiety state related to COVID-19 crisis, we investigated how home quarantine affected sleep parameters in healthy individuals. Methods 160 healthy individuals who were in home quarantine in April 2020 for at least one month participated in this study. Participants rated and compared their quantitative sleep parameters (time to go to bed, sleep duration, getting-up time) and sleep quality factors, pre-and during home quarantine due to the COVID-19 pandemic. Furthermore, participants chronotype was determined to see if sleep parameters are differentially affected in different chronotypes. Results The time to fall asleep and get-up in the morning were significantly delayed in all participants, indicating a significant circadian misalignment. Sleep quality was reported to be significantly poorer in all participants and chronotypes, and included more daily disturbances (more sleep disturbances, higher daily dysfunctions due to low quality of sleep) and less perceived sleep quality (lower subjective sleep quality, longer time taken to fall asleep at night, more use of sleep medication for improving sleep quality) during home quarantine. Conclusions Home quarantine due to COVID-19 pandemic has a detrimental impact on sleep quality. Online interventions including self-help sleep programs, stress management, relaxation practices, stimulus control, sleep hygiene, and mindfulness training are available interventions in the current situation.", "qid": 12, "docid": "agwhkfcb", "rank": 21, "score": 8.217000007629395}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index &#8805;40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 12, "docid": "3jwl97qb", "rank": 22, "score": 8.089599609375}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy. Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index \u226540), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 12, "docid": "7ofa04l1", "rank": 23, "score": 8.089598655700684}, {"content": "Title: Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic Content: The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems. COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation. People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important.", "qid": 12, "docid": "i5b0k41k", "rank": 24, "score": 8.075799942016602}, {"content": "Title: Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic Content: The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems.COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation.People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important.", "qid": 12, "docid": "wldxibrt", "rank": 25, "score": 8.075798988342285}, {"content": "Title: The TVBG-SEIR spline model for analysis of COVID-19 spread, and a Tool for prediction scenarios Content: Mathematical models are traditionally used to analyze the long-term global evolution of epidemics, to determine the potential and severity of an outbreak, and to provide critical information for identifying the type of disease interventions and intensity. One of the widely used mathematical models of long-term spreading of epidemics are the so-called deterministic compartmental models (SIR/SEIR type models). One of the main purposes of applying such models is to assess how the expensive restriction measures imposed by the authorities (home and social isolation/quarantine, travel restrictions, etc.) can effectively reduce the control reproduction number of the disease and its transmission risk. However the classical SIR/SEIR models have been primarily studied in what may be called stationary case, where the main parameters, the Transmission rate Beta (reflecting the virus spread by infected individuals) and the Removed rate Gamma (reflecting the hospitalization/isolation measures) remain constant during the whole period of interest. Hence, it is important to extend the classical SIR/SEIR models by creating new ansatzes for the dynamics of the transmission rates Beta(t) (which we will call further just Beta) and removed rates Gamma(t) (which we will call further just Gamma). The main purpose of the present research is to introduce a spline-based SEIR model with Time-varying Beta and Gamma parameters, or abbreviated TVBG-SEIR model, which is used to estimate the practical implications of the public health interventions and measures. We have designed a Tool based on the TVBG-SEIR model, which may be used as a Decision Support Tool to assist the health decision- and policy-makers in creating predictive scenarios.", "qid": 12, "docid": "9b49796l", "rank": 26, "score": 8.067000389099121}, {"content": "Title: If you ask them, will they come? Predictors of quarantine compliance during a hypothetical avian influenza pandemic: results from a statewide survey. Content: BACKGROUND An influenza pandemic, such as that of the H1N1 virus, raises questions about how to respond effectively to a lethal outbreak. Most plans have focused on minimizing impact by containing the virus through quarantine, but quarantine has not been used widely in the United States and little is known about what would be the public's response. The purpose of this study was to investigate factors that influence an individual's decision to comply with a hypothetical avian influenza quarantine order. METHODS A total of 1204 adult Pennsylvania residents participated in a random digit dial telephone sample. The residents were interviewed regarding their attitudes about and knowledge of avian influenza and about compliance with quarantine orders, including staying at home or traveling to a government-designated facility. RESULTS Analysis of variance showed differences among demographic groups in willingness to comply with quarantine orders, with women and individuals not presently employed more willing to stay at home or to travel to a government-designated facility if ordered. Those who did not regularly attend religious services were significantly less willing than those who did attend regularly to comply with any type of quarantine order. Regression analysis indicated that demographic variables, overall knowledge of avian influenza, attitudes about its severity, and the belief that the respondent and/or his or her significant other(s) may contract it were predictive. CONCLUSIONS The results of this study can provide health planners and policy makers with information for improving their efforts to conduct a quarantine successfully, including crafting messages and targeting information to certain groups of people to communicate risk about the epidemic.", "qid": 12, "docid": "5jjstgkl", "rank": 27, "score": 8.038000106811523}, {"content": "Title: Addressing the Gaps in Preparation for Quarantine Content: INTRODUCTION: In the event of an outbreak of a communicable respiratory illness, quarantine may become necessary. The New York Institute for All Hazard Preparedness (NYIAHP) of the State University of New York (SUNY) Downstate Medical Center, in cooperation with the New York City Department of Health and Mental Hygiene's Healthcare Emergency Preparedness Program, (NYC DOHMH-HEPP) quarantine working group, has developed a series of clinical protocols to help health care facilities respond to such an event. PROBLEM: Two full-scale exercises (FSEs) were designed and conducted a year apart in the quarantine unit at Kings County Hospital Center (KCHC) to test the efficacy and feasibility of these quarantine protocols. The goal of these exercises was to identify the gaps in preparedness for quarantine and increase hospital readiness for such an event. METHODS: Evaluators monitored for efficient management of critical physical plants, personnel and material resources. Players were expected to integrate and practice emergency response plans and protocols specific to quarantine. In developing the exercise objectives, five activities were selected for evaluation: Activation of the Unit, Staffing, Charting/Admission, Symptom Monitoring and Infection Control, and Client Management. RESULTS: The results of the initial FSE found that there were incomplete critical tasks within all five protocols: These deficiencies were detailed in an After Action Report and an Improvement Plan was presented to the KCHC Disaster Preparedness Committee a month after the initial FSE. In the second FSE a year later, all critical tasks for Activation of the unit, Staffing and Charting/Admission were achieved. Completion of critical tasks related to Symptom Monitoring and Infection Control and Client Management was improved in the second FSE, but some tasks were still not performed appropriately. CONCLUSION: In short, these exercises identified critical needs in disaster preparedness of the KCHC Quarantine Unit. The lessons learned from this logistical exercise enabled the planning group to have a better understanding of leadership needs, communication capabilities, and infection control procedures. Kings County Hospital Center performed well during these exercises. It was clear that performance in the second exercise was improved, and many problems noted in the first exercise were corrected. Staff also felt better prepared the second time. This supports the idea that frequent exercises are vital to maintain disaster readiness. R Nathawad, PM Roblin, D Pruitt, B Arquilla. Addressing the gaps in preparation for quarantine. Prehosp Disaster Med. 2013;28(2):1-7 23158909.", "qid": 12, "docid": "hdbbgee2", "rank": 28, "score": 8.028900146484375}, {"content": "Title: All Feet On Deck-The Role of Podiatry During the COVID-19 Pandemic: Preventing hospitalizations in an overburdened healthcare system, reducing amputation and death in people with diabetes. Content: The COVID-19 pandemic is driving significant change in the healthcare system and disrupting the best practices for diabetic limb preservation, leaving large numbers of patients without care. Patients with diabetes and foot ulcers are at increased risk for infections, hospitalization, amputations, and death. Podiatric care is associated with fewer diabetes-related amputations, ER visits, hospitalizations, length-of-stay, and costs. But podiatrists must mobilize and adopt the new paradigm of shifts away from hospital care to community-based care. Implementing the proposed Pandemic Diabetic Foot Triage System, in-home visits, higher acuity office visits, telemedicine, and remote patient monitoring can help podiatrists manage patients while reducing the COVID-19 risk. The goal of podiatrists during the pandemic is to reduce the burden on the healthcare system by keeping diabetic foot and wound patients safe, functional, and at home.", "qid": 12, "docid": "0mhznhsl", "rank": 29, "score": 8.027600288391113}, {"content": "Title: All Feet On Deck-The Role of Podiatry During the COVID-19 Pandemic: Preventing hospitalizations in an overburdened healthcare system, reducing amputation and death in people with diabetes Content: The COVID-19 pandemic is driving significant change in the healthcare system and disrupting the best practices for diabetic limb preservation, leaving large numbers of patients without care. Patients with diabetes and foot ulcers are at increased risk for infections, hospitalization, amputations, and death. Podiatric care is associated with fewer diabetes-related amputations, ER visits, hospitalizations, length-of-stay, and costs. But podiatrists must mobilize and adopt the new paradigm of shifts away from hospital care to community-based care. Implementing the proposed Pandemic Diabetic Foot Triage System, in-home visits, higher acuity office visits, telemedicine, and remote patient monitoring can help podiatrists manage patients while reducing the COVID-19 risk. The goal of podiatrists during the pandemic is to reduce the burden on the healthcare system by keeping diabetic foot and wound patients safe, functional, and at home.", "qid": 12, "docid": "1yv3v8w7", "rank": 30, "score": 8.027599334716797}, {"content": "Title: Impacts of Early Interventions on the Age-Specific Incidence of COVID-19 in New York, Los Angeles, Daegu and Nairobi Content: Background COVID-19 has caused an unprecedented public health crisis and economic shock to the global economy. While many countries were affected, regions with an older population and weaker public health interventions tended to suffer more morbidity and mortality. Here we model and quantify the age-specific incidence of COVID-19 in four pandemic cities under different interventions. Methods We developed an age-specific and multiple-stage susceptible-exposed-infected-recovered-hospitalized-quarantined-dead (SEIR-HQD) dynamical systems model expanded from the more basic SEIR model by incorporating location- and age-specific contact matrices to estimate the outcomes of COVID-19. Utilizing latest estimates of epidemiological parameters and demographic data, we model the potential effects of various interventions in four representative cities with different population structures - New York, Los Angeles, Daegu and Nairobi. We compared the effects of different interventions in the age-structure populations specific to each city. These policy options are then applied to determine the potential for effective containment. We model these dynamic policy scenarios to assess the risks of less-stringent social distancing, as has been proposed by those arguing to enhance economic activity over public health and safety. Finally, we explored the health impacts of different policy action timelines to understand the benefits of early interventions. Findings We find the spread of COVID-19 to be dramatically different in the regions modeled, with the primary drivers the variation of population age structures, and the dynamics of interactions of the younger demographics, whose higher interaction rates can lead to increasing transmission rates across these communities. A city with younger citizens may also have fewer hospitalized cases and deaths. Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities. The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections. Interpretation Moderate social distancing together with high quarantine rates was effective in each of the four cities. COVID-19 caused more deaths and hospitalization in cities with an ageing population than those with a younger population. However, in the cities with a younger population, there is a clear need to implement a social distancing strategy that is even more strict due to the higher transmission rates among younger people. Cities with more older people should prepare more hospital beds and healthcare facilities to save people who are in critical conditions. Cities with ageing population should take targeted action for the elderly to avoid the severe impacts on the vulnerable populations. Increasing quarantine rate is an effective strategy to avoid the substantial infection while also does not influence the economy fiercely. We recommend countries or regions experiencing, or likely to experience the rapid spread of COVID-19, to implement combination of multiple strategies in the early stage of the breakout which can avoid over 90% of infected cases.", "qid": 12, "docid": "5zg3xr69", "rank": 31, "score": 8.024299621582031}, {"content": "Title: Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients Content: Abstract Objectives This study aimed to assess the immediate stress and psychological impact experienced by quarantined patients undergoing hemodialysis and university hospital workers who treated patients Middle East respiratory syndrome (MERS) during its outbreak. Design The group of subjects consisted of 1800 hospital practitioners and 73 quarantined patients undergoing hemodialysis. The Impact of Events Scale\u2013Revised (IES-R) was administered to the practitioners twice, once during the hospital shutdown and again one month after the shutdown. The Mini International Neuropsychiatric Interview and Hospital Anxiety and Depression Scale were administered to patients undergoing hemodialysis. Results During the initial stages of the MERS outbreak, healthcare workers who performed MERS-related tasks scored significantly higher on the total IES-R and its subscales. In the second assessment of the high-risk group, the sleep and numbness subscale scores from the IES-R differed depending on the implementation of home quarantine, and the intrusion subscale scores differed depending on the performance of MERS-related tasks. Conclusion Medical staff that performed MERS-related tasks showed the highest risk for post-traumatic stress disorder symptoms even after time had elapsed. The risk increased even after home quarantine. Prompt and continuous psychiatric intervention is needed in high mortality infectious disease outbreaks.", "qid": 12, "docid": "zmfcfbo8", "rank": 32, "score": 8.02299976348877}, {"content": "Title: Glycemic control in type 1 diabetes mellitus during COVID-19 quarantine and the role of in-home physical activity. Content: BACKGROUND In order to limit the spread of COVID-19, governments have ordered a series of restrictions that may affect glycemic control in individuals with T1DM, since physical activity (PA) was not allowed outside home. MATERIALS AND METHODS We retrospectively evaluated glycemic control of individuals with T1DM using HCL system in the period before the SARS-CoV-2 outbreak in Italy (February 10th - 23rd, 2020 - Time 1), when movements were only reduced (February 24th - March 8th, 2020 - Time 2) and during complete lockdown (March 9th-22nd, 2020 - Time 3). Information about regular PA (at least 3 hours per week) prior and during the quarantine were collected. RESULTS The study included 13 individuals with a median age of 14.2 years and a good glycemic control at baseline (GMI 7%, TIR 68%, TBR 2%). All individuals continued to show good glycemic control throughout the study period. There was an increase in TIR during the study period (+3%) and TIR was significantly higher in Time 3 (72%) than in Time 2 (66%). TBR was significantly lower in Time 3 (1%) both compared to Time 1 and Time 2 (2%). A meaningful variance in TIR at Time 3 between individuals who performed or not PA during quarantine and a significant increase in TIR between Time 2 and Time 3 both in individuals doing PA at baseline and during quarantine, was found. At logistic regression, only the presence of PA during quarantine significantly predicted a TIR >70 %. CONCLUSIONS Glycemic control of T1DM in adolescents using HCL system did not worsen during the restrictions due to COVID-19 pandemics and further improved in those who continued physical activity during the quarantine. Maintaining regular physical activity in a safe home environment is an essential strategy for young individuals with T1DM during the COVID-19 crisis.", "qid": 12, "docid": "4vhlgqig", "rank": 33, "score": 7.990799903869629}, {"content": "Title: Philippine Teachers\u2019 Practices to Deal with Anxiety amid COVID-19 Content: School closures, home quarantine, and social distancing implemented worldwide can cause a sudden anxiety even among teachers. A designed online survey collected data from Filipino teachers\u2019 practices on how they deal with anxiety due to the COVID-19 outbreak. The practices include information seeking, preventive measures, and other coping mechanisms to deal with anxiety during the quarantine period. Results revealed that teachers practice virtual learning, communicate with the professional community, adhere to quarantine requirements, and find purposeful activities to deal with anxiety due to the suspension of national school-related activities in the country brought by the pandemic.", "qid": 12, "docid": "csd3p35k", "rank": 34, "score": 7.982999801635742}, {"content": "Title: Redesigning Primary Care to Address the COVID-19 Pandemic in the Midst of the Pandemic. Content: During a pandemic, primary care is the first line of defense. It is able to reinforce public health messages, help patients manage at home, and identify those in need of hospital care. In response to the COVID-19 pandemic, primary care scrambled to rapidly transform itself and protect clinicians, staff, and patients while remaining connected to patients. Using the established public health framework for addressing a pandemic, we describe the actions primary care needs to take in a pandemic. Recommended actions are based on observed experiences of the authors' primary care practices and networks. Early in the COVID-19 pandemic, tasks focused on promoting physical distancing and encouraging patients with suspected illness or exposure to self-quarantine. Testing was not available and contract tracing was not possible. As the pandemic spread, in-person care was converted to virtual care using telehealth. Practices remained connected to patients using registries to reach out to those at risk for infection, with uncontrolled chronic conditions, or were socially vulnerable. Practices managed most patients with suspected COVID-19 at home. As the pandemic decelerates, practices are now preparing to address the direct and indirect consequences-complications from COVID-19 infections, missed treatment for acute problems, inadequate prevention, uncontrolled chronic disease, mental illness, and greater social needs. Throughout, practices bore tremendous financial burden, laying off staff or even closing at a time when most needed. Primary care must learn from this experience and be ready for the next pandemic. Policymakers and payers cannot fail primary care during their next time of need.", "qid": 12, "docid": "d7jmakcj", "rank": 35, "score": 7.960999965667725}, {"content": "Title: Reflection on SARS precautions in a severe intellectual disabilities hospital in Hong Kong Content: Background Hong Kong went through a battle with a new respiratory disease, severe acute respiratory syndrome (SARS), from March to June 2003. All clinical settings, including rehabilitative and infirmary setting, have actively involved in fighting against the infection. The intent of this paper was to reflect on the SARS precautionary measures that had been taken in a severe intellectual disabilities hospital in Hong Kong. Methods A review on six SARS precautionary measures were conducted. They were assessment of risk, formulation of operational guidelines, implementation of infection control measures, education and training of staff, conducting audits and carrying out environmental improvement work. Results Patients were at risk of getting infected from carers, visitors, volunteers, and staff and patients of general hospitals. A SARS Quarantine Unit, isolation ward, was opened to isolate patients who might have had close contact with SARS patients during a stay in a general hospital or when they returned from home leave. Undoubtedly, both staff and relatives participated in preventing the patients from being infected. No day leave and home leave was reported and the number of hospitalization in general hospital was decreased during the critical period. Three infection control audits were conducted and improvement work was carried out subsequently. Conclusion The practice of grouping within a standard isolation room is recommended to continue in the future. Moreover, intensive infection control training for all staff is of highest importance to safeguard the health of both staff and patient.", "qid": 12, "docid": "ax7tm4os", "rank": 36, "score": 7.937600135803223}, {"content": "Title: Glycemic Control in Type 1 Diabetes Mellitus During COVID-19 Quarantine and the Role of In-Home Physical Activity Content: Background: To limit the spread of coronavirus disease 2019 (COVID-19), governments have ordered a series of restrictions that may affect glycemic control in individuals with type 1 diabetes mellitus (T1DM), since physical activity (PA) was not allowed outside home. Methods: We retrospectively evaluated glycemic control of individuals with T1DM using hybrid closed loop (HCL) system in the period before the SARS-CoV-2 outbreak in Italy (February 10-23, 2020-Time 1), when movements were only reduced (February 24-March 8, 2020-Time 2) and during complete lockdown (March 9-22, 2020-Time 3). Information about regular PA (at least 3 h per week) prior and during the quarantine was collected. Results: The study included 13 individuals with a median age of 14.2 years and a good glycemic control at baseline (glucose management indicator of 7%, time in range [TIR] of 68%, time below range [TBR] of 2%). All individuals continued to show good glycemic control throughout the study period. There was an increase in TIR during the study period (+3%) and TIR was significantly higher during Time 3 (72%) than during Time 2 (66%). TBR was significantly lower during Time 3 (1%) both compared with Time 1 and Time 2 (2%). A meaningful variance in TIR at Time 3 between individuals who performed or not PA during quarantine and a significant increase in TIR between Time 2 and Time 3 in individuals both doing PA at baseline and during quarantine was found. At logistic regression, only the presence of PA during quarantine significantly predicted a TIR >70%. Conclusions: Glycemic control of T1DM in adolescents using HCL system did not worsen during the restrictions due to COVID-19 pandemics and further improved in those who continued PA during the quarantine. Maintaining regular PA in a safe home environment is an essential strategy for young individuals with T1DM during the COVID-19 crisis.", "qid": 12, "docid": "f6kaef4a", "rank": 37, "score": 7.902100086212158}, {"content": "Title: The psychological impact of quarantine and how to reduce it: rapid review of the evidence Content: The December, 2019 coronavirus disease outbreak has seen many countries ask people who have potentially come into contact with the infection to isolate themselves at home or in a dedicated quarantine facility. Decisions on how to apply quarantine should be based on the best available evidence. We did a Review of the psychological impact of quarantine using three electronic databases. Of 3166 papers found, 24 are included in this Review. Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.", "qid": 12, "docid": "nyan7jnt", "rank": 38, "score": 7.898399829864502}, {"content": "Title: Chapter 7 Indoor Environmental Quality (IEQ) Content: Abstract From the outset, Chapter 7 tries to explain what is understood by indoor environmental quality (IEQ) and the various factors that impact it, as well as the best current approaches employed to achieving optimum IEQ. The causes of building-related illness (BRI) and sick building syndrome (SBS), which appear to be on the increase, are explained and analyzed. The chapter also focuses on the need for a building\u2019s interior air quality, as this is one of the most pivotal factors in maintaining building occupants\u2019 safety, productivity, and well-being. Other important factors that are focused on are ventilation and filtration, including air cleaners and ventilation systems. The leading inorganic indoor contaminants are discussed such as asbestos, radon, and lead, exposure to which can create significant health risks. Likewise, organic contaminants including aldehydes, volatile organic compounds/semivolatile organic compounds, and pesticides are examined and analyzed. Several combustion-generated contaminates such as carbon dioxide, water, carbon monoxide, and nitrogen oxides are also looked into. Toward the end of the chapter, the best practices for IEQ are outlined and discussed.", "qid": 12, "docid": "3zzqfy1e", "rank": 39, "score": 7.886600017547607}, {"content": "Title: COVID-19 created chaos across the globe: Three novel quarantine epidemic models Content: The latest version of human coronavirus said to be COVID-19 came out as a sudden pandemic disease within human population and in the absence of vaccination and proper treatment till date, it daunting threats heavily to human lives, infecting more than 12, 11, 214 people and death more than 67, 666 people in 208 countries across the globe as on April 06, 2020, which is highly alarming. When no treatment or vaccine is available till date and to avoid COVID-19 to be transmitted in the community, social distancing is the only way to prevent the disease, which is well taken into account in our novel epidemic models as a special compartment, that is, home isolation. Based on the transmitting behaviour of COVID-19 in the human population, we develop three quarantine models of this pandemic taking into account the compartments: susceptible population, immigrant population, home isolation population, infectious population, hospital quarantine population, and recovered population. Local and global asymptotic stability is proved for all the three models. Extensive numerical simulations are performed to establish the analytical results with suitable examples. Our research reveals that home isolation and quarantine to hospitals are the two pivot force-control policies under the present situation when no treatment is available for this pandemic.", "qid": 12, "docid": "8y92vh5y", "rank": 40, "score": 7.846099853515625}, {"content": "Title: COVID-19 created chaos across the globe: Three novel quarantine epidemic models Content: The latest version of human coronavirus said to be COVID-19 came out as a sudden pandemic disease within human population and in the absence of vaccination and proper treatment till date, it daunting threats heavily to human lives, infecting more than 12, 11, 214 people and death more than 67, 666 people in 208 countries across the globe as on April 06, 2020, which is highly alarming. When no treatment or vaccine is available till date and to avoid COVID-19 to be transmitted in the community, social distancing is the only way to prevent the disease, which is well taken into account in our novel epidemic models as a special compartment, that is, home isolation. Based on the transmitting behavior of COVID-19 in the human population, we develop three quarantine models of this pandemic taking into account the compartments: susceptible population, immigrant population, home isolation population, infectious population, hospital quarantine population, and recovered population. Local and global asymptotic stability is proved for all the three models. Extensive numerical simulations are performed to establish the analytical results with suitable examples. Our research reveals that home isolation and quarantine to hospitals are the two pivot force-control policies under the present situation when no treatment is available for this pandemic.", "qid": 12, "docid": "ilkmkun5", "rank": 41, "score": 7.846098899841309}, {"content": "Title: [The application of a systematic-dynamic model to study the computer simulation of severe acute respiratory syndrome transmission and the impact of control measures]. Content: OBJECTIVE (1) Building a macroscopical systematic-dynamic model of severe acute respiratory syndrome (SARS) transmission and disease control process. (2) To determine key variables on the control of SARS epidemic through computer simulation methodology, especially to analyze the effect of \"screening for fever\" practice during the epidemics. (3) To provide evidence for related decision-making. METHODS Parameters in the model were collected from local hospitals and municapal CDC through interview, questionnaire survey, literature review and case analysis. A systematic-dynamic model was built under similar studies. 'What-if' analysis was used during the simulation process. RESULTS (1) The mean duration between disease onset and hospital admission, rate of contacts of each infectious individual as well as the rate of contacts in hospital of each infectious individual appeared to be the key variables in the process of SARS transmission. (2) Physician's alertness/sense and practice of self-protection on SARS, measures on quarantine and isolation to the patients, ventilation and disinfection process in the wards appeared to be the key variables for the control of epidemics. (3) \"Screening for fever\" practice on each patient at the entrance of the hospital did not seem to act as an important factor to the control of the epidemics. CONCLUSION The health system in Beijing can control SARS epidemic rapidly based on current applied disease control measures and plan.", "qid": 12, "docid": "21deuayd", "rank": 42, "score": 7.822500228881836}, {"content": "Title: Impact of COVID-19 pandemic on the daily management of biotechnological therapy in inflammatory bowel disease patients: Reorganisational response in a high-volume Italian inflammatory bowel disease centre Content: The coronavirus disease 2019 (COVID-19) pandemic is having a major clinical as well as organisational impact on the national health-care system in Italy, particularly in high-volume hospitals which are usually active for many essential clinical needs, including inflammatory bowel disease (IBD). Here, we report major clinical and organisational challenges at a high-volume Italian IBD centre one month after the start of the Italian government's restrictions due to the COVID-19 pandemic. All routine follow-up IBD visits of patients in remission were cancelled or rescheduled for 8-12 weeks' time. However, access to the hospital for therapy or for unstable/relapsing patients was not considered postponable. Everyone attending the centre (e.g. physicians, nurses, administrative personnel and patients) were advised to respect the general recommended rules for hand hygiene and social distancing, to disclose if they had a fever or cough or flu-like symptoms and to wear a surgical mask and gloves. At the entrance of the therapy area, a control station was set up in order to double-check all patients with a clinical interview and conduct thermal scanning. A total of 1451 IBD patients under biotechnological or experimental therapy actively followed in the CEMAD IBD centre were included in the study. About 65% of patients maintained their appointment schedules without major problems, while in 20% of cases planned infusions were delayed because of the patient's decision or practical issues. About 10% of patients receiving subcutaneous therapy were allowed to collect their medicine without a follow-up visit. Finally, 10% of patients living outside the Lazio region requested access to their therapy at a local centre closer to their home. At present, five patients have been found to be positive for SARS-CoV-2 infection but with minimal symptoms, 22 are in 'quarantine' for contact considered to be 'at risk' for the infection. Up to now, none of them has experienced significant symptoms. This study represents the first observational detailed report about short-term impact of the COVID-19 pandemic on patient organisation and management in a high-volume IBD centre.", "qid": 12, "docid": "itqk0ju3", "rank": 43, "score": 7.8043999671936035}, {"content": "Title: Impact of COVID-19 pandemic on the daily management of biotechnological therapy in inflammatory bowel disease patients: Reorganisational response in a high-volume Italian inflammatory bowel disease centre. Content: The coronavirus disease 2019 (COVID-19) pandemic is having a major clinical as well as organisational impact on the national health-care system in Italy, particularly in high-volume hospitals which are usually active for many essential clinical needs, including inflammatory bowel disease (IBD). Here, we report major clinical and organisational challenges at a high-volume Italian IBD centre one month after the start of the Italian government's restrictions due to the COVID-19 pandemic. All routine follow-up IBD visits of patients in remission were cancelled or rescheduled for 8-12 weeks' time. However, access to the hospital for therapy or for unstable/relapsing patients was not considered postponable. Everyone attending the centre (e.g. physicians, nurses, administrative personnel and patients) were advised to respect the general recommended rules for hand hygiene and social distancing, to disclose if they had a fever or cough or flu-like symptoms and to wear a surgical mask and gloves. At the entrance of the therapy area, a control station was set up in order to double-check all patients with a clinical interview and conduct thermal scanning. A total of 1451 IBD patients under biotechnological or experimental therapy actively followed in the CEMAD IBD centre were included in the study. About 65% of patients maintained their appointment schedules without major problems, while in 20% of cases planned infusions were delayed because of the patient's decision or practical issues. About 10% of patients receiving subcutaneous therapy were allowed to collect their medicine without a follow-up visit. Finally, 10% of patients living outside the Lazio region requested access to their therapy at a local centre closer to their home. At present, five patients have been found to be positive for SARS-CoV-2 infection but with minimal symptoms, 22 are in 'quarantine' for contact considered to be 'at risk' for the infection. Up to now, none of them has experienced significant symptoms. This study represents the first observational detailed report about short-term impact of the COVID-19 pandemic on patient organisation and management in a high-volume IBD centre.", "qid": 12, "docid": "m2ewf7wt", "rank": 44, "score": 7.804399013519287}, {"content": "Title: COVID-19: A case report from Bangladesh perspective Content: Abstract A 34-year-old man without any significant medical history or comorbidities, suddenly developed fever, and shortness of breath, thereby admitted to the emergency department of a tertiary care hospital, Dhaka, Bangladesh. He had neither a history of traveling to Coronavirus disease (COVID) prone areas nor a direct contact of COVID positive patients. His chest X-ray revealed ground-glass opacity in the right middle and lower zone of the lung. The first polymerase chain reaction (PCR) test on throat and nasal swabs for the COVID upon admission was negative. Based on the chest X-ray result, RT-PCR was done again resulted positive. The patient was primarily treated with chloroquine and azithromycin. On full recovery, he was discharged from the hospital on day 12, after two subsequent throat swab samples tested negative by PCR (24 hours apart). He was encouraged to maintain home quarantine for at least the next 14 days. SARS-CoV-2 RNA by swab remained negative and the blood sample shows the presence of antibody (both IgM and IgG) in his follow-up visit (after 7 days of hospital discharge).", "qid": 12, "docid": "0i5zlvgn", "rank": 45, "score": 7.792099952697754}, {"content": "Title: COVID-19: A case report from Bangladesh perspective Content: A 34-year-old man without any significant medical history or comorbidities, suddenly developed fever, and shortness of breath, thereby admitted to the emergency department of a tertiary care hospital, Dhaka, Bangladesh. He had neither a history of traveling to Coronavirus disease (COVID) prone areas nor a direct contact of COVID positive patients. His chest X-ray revealed ground-glass opacity in the right middle and lower zone of the lung. The first polymerase chain reaction (PCR) test on throat and nasal swabs for the COVID upon admission was negative. Based on the chest X-ray result, RT-PCR was done again resulted positive. The patient was primarily treated with chloroquine and azithromycin. On full recovery, he was discharged from the hospital on day 12, after two subsequent throat swab samples tested negative by PCR (24 hours apart). He was encouraged to maintain home quarantine for at least the next 14 days. SARS-CoV-2 RNA by swab remained negative and the blood sample shows the presence of antibody (both IgM and IgG) in his follow-up visit (after 7 days of hospital discharge).", "qid": 12, "docid": "vr0xoohd", "rank": 46, "score": 7.7920989990234375}, {"content": "Title: \u201cQuarantine during COVID-19 outbreak: changes in Diet and physical activity increase the risk of cardiovascular disease\u201d Content: Abstract Aims CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several Governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. Data Synthesis Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behaviour while at home. Conclusions Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy Diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.", "qid": 12, "docid": "0croajal", "rank": 47, "score": 7.742599964141846}, {"content": "Title: \"Quarantine during COVID-19 outbreak: Changes in diet and physical activity increase the risk of cardiovascular disease\" Content: AIMS: CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. DATA SYNTHESIS: Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home. CONCLUSION: Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.", "qid": 12, "docid": "jt7ctj2z", "rank": 48, "score": 7.742599010467529}, {"content": "Title: epic2: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England Content: Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001.1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and non-experimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Healthand Clinical Excellence).2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be made to some guideline recommendations following a synopsis of the evidence underpinning the guidelines. These updated national guidelines (epic2) provide comprehensive recommendations for preventing HCAI in hospitals and other acute care settings based on the best currently available evidence. Because this is not always the best possible evidence, we have included a suggested agenda for further research in each section of the guidelines. National evidence-based guidelines are broad principles of best practice which need to be integrated into local practice guidelines. To monitor implementation, we have suggested key audit criteria for each section of recommendations. Clinically effective infection prevention and control practice is an essential feature of protecting patients. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of healthcare in NHS hospitals in England can be minimised.", "qid": 12, "docid": "757mh2mh", "rank": 49, "score": 7.7332000732421875}, {"content": "Title: COVID-19 and quarantine orders: A practical approach Content: Quarantine is a very effective method for containing the spread of highly infectious diseases in large populations during a pandemic, but it is only effective if properly implemented. The co-operation and compliance of people entering quarantine are critical to its success. However, owing to the isolating and social distancing nature of quarantine, it often leads to extreme economic hardship and shortages in basic needs such as food, medicine, water and communication- A nd to the curtailment of certain universal social norms such as attending a parent's funeral. To escape these hardships, people often refuse to enter voluntary quarantine, or breach quarantine rules. In these circumstances, health authorities are obliged to act in the best interests of the public and obtain court orders to force some people into quarantine. In further extreme circumstances, when a national lockdown is ordered, non-compliance with quarantine measures may result in arrests and penalties. The scope of this article is limited to the period prior to and following such a lockdown, during which quarantine may still be vital for the containment of COVID-19. Because a quarantine order will deprive an individual of his or her freedom, this must be carefully balanced with the public interest. This article explains the legal and ethical considerations of this balancing exercise and provides practical guidance for obtaining quarantine orders.", "qid": 12, "docid": "q49c71l1", "rank": 50, "score": 7.723800182342529}, {"content": "Title: Kidney Allograft Recipients Diagnosed with Coronavirus Disease-2019: A Single Center Report Content: Background: Organ graft recipients receiving immunosuppressive therapy are likely to be at heighted risk for the Coronavirus Disease 2019 (Covid-19) and adverse outcomes including death. It is therefore important to characterize the clinical course and outcome of Covid-19 in this vulnerable population and identify therapeutic strategies that are safe. Methods: We performed a retrospective chart review of 54 adult kidney transplant patients diagnosed with Covid-19 and managed in New York State, the epicenter of Covid-19 pandemic. The patients were evaluated by video visits, phone interviews, or in the Emergency Room for respiratory illness symptoms consistent with Covid-19 from March 13, 2020 to April 20, 2020. Characteristics of the patients were stratified by hospitalization status and disease severity. Clinical course including alterations in immunosuppressive therapy were retrieved from their electronic medical records. Primary outcomes included recovery from Covid-19 symptoms, acute kidney injury, graft failure, and case fatality rate. Results: Of the 54 SARS-Cov-2 positive kidney transplant recipients, 39 with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. Hospitalized patients compared to non-hospitalized patients were more likely to be male, of Hispanic ethnicity, and to have cardiovascular disease. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients, and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs. 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients and only one of 15 non-hospitalized patients. Acute kidney injury occurred in 51% of hospitalized patients. Patients with severe disease were more likely to have elevations in inflammatory biomarkers at presentation. At a median of 21 days follow up, 67% of patients have had their symptoms resolved or improved and 33% have persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired. Conclusions: Clinical presentation of Covid-19 in kidney transplant recipients was similar to what has been described in the general population. The case fatality rate in our entire cohort of 54 kidney transplant recipients was reassuringly low and patients with mild symptomology could be successfully managed at home. Data from the pilot study suggest that a strategy of systematic screening and triage to inpatient or outpatient care, close monitoring, and judicious use of immunosuppressive drugs rather than cessation is beneficial.", "qid": 12, "docid": "y6rfq2mx", "rank": 51, "score": 7.718500137329102}, {"content": "Title: Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings Content: Isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures - including novel digital tracing approaches and less intensive physical distancing - may be required to reduce transmission. Using a model of individual-level transmission stratified by setting (household, work, school, other) based on BBC Pandemic data from 40,162 UK participants, we simulated the impact of a range of different testing, isolation, tracing and physical distancing scenarios. As well as estimating reduction in effective reproduction number, we estimated, for a given level of COVID-19 incidence, the number of contacts that would be newly quarantined each day under different strategies. Under optimistic but plausible assumptions, we estimated that combined testing and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50-65% compared to 2-30%). If limits are placed on gatherings outside of home/school/work (e.g. maximum of 4 daily contacts in other settings), then manual contact tracing of acquaintances only could have a similar effect on transmission reduction as detailed contact tracing. In a scenario where there were 10,000 new symptomatic cases per day, we estimated in most contact tracing strategies, 140,000 to 390,000 contacts would be newly quarantined each day. Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimates that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number that is below one in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control.", "qid": 12, "docid": "bwmpamea", "rank": 52, "score": 7.688700199127197}, {"content": "Title: Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study Content: BACKGROUND: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40\u00e2\u0080\u0088162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15\u00e2\u0080\u0088000-41\u00e2\u0080\u0088000 contacts would be newly quarantined each day. INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.", "qid": 12, "docid": "29pj30j9", "rank": 53, "score": 7.639400005340576}, {"content": "Title: Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study. Content: BACKGROUND The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000-41 000 contacts would be newly quarantined each day. INTERPRETATION Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.", "qid": 12, "docid": "s4lsbl1j", "rank": 54, "score": 7.63939905166626}, {"content": "Title: Clinical Practice Guideline for the Evaluation of Fever and Infection in Older Adult Residents of Long\u2010Term Care Facilities: 2008 Update by the Infectious Diseases Society of America Content: Residents of long\u2010term care facilities (LTCFs) are at great risk for infection. Most residents are older and have multiple comorbidities that complicate recognition of infection; for example, typically defined fever is absent in more than one\u2010half of LTCF residents with serious infection. Furthermore, LTCFs often do not have the on\u2010site equipment or personnel to evaluate suspected infection in the fashion typically performed in acute care hospitals. In recognition of the differences between LTCFs and hospitals with regard to hosts and resources present, the Infectious Diseases Society of America first provided guidelines for evaluation of fever and infection in LTCF residents in 2000. The guideline presented here represents the second edition, updated by data generated over the intervening 8 years. It focuses on the typical elderly person institutionalized with multiple chronic comorbidities and functional disabilities (e.g., a nursing home resident). Specific topic reviews and recommendations are provided with regard to what resources are typically available to evaluate suspected infection, what symptoms and signs suggest infection in a resident of an LTCF, who should initially evaluate the resident with suspected infection, what clinical evaluation should be performed, how LTCF staff can effectively communicate about possible infection with clinicians, and what laboratory tests should be ordered. Finally, a general outline of how a suspected outbreak of a specific infectious disease should be investigated in an LTCF is provided.", "qid": 12, "docid": "wkhxbcue", "rank": 55, "score": 7.632800102233887}, {"content": "Title: Do Quarantine Experiences and Attitudes Towards COVID-19 Affect the Distribution of Mental Health in China? A Quantile Regression Analysis Content: While quarantine has become a widely used control strategy during the outbreak of the 2019 novel coronavirus disease (COVID-19), empirical research on whether and to what extent quarantine and attitudes towards COVID-19 affect mental health is scant. Using a cross-sectional online survey, this paper is the first from the Chinese outbreak to investigate how quarantine experiences and attitudes towards COVID-19 are related to mental health, and how these relationships change across the distribution of mental health scores. Using quantile regression analysis, we found that home self-quarantine is associated with a decrease in depression and an increase in happiness, while community-level quarantine is associated with decreased happiness, especially for those in the lower happiness quantile. We also found that favorable attitudes towards COVID-19 regarding the credibility of real-time updates and confidence in the epidemic control are associated with lower levels of depression and higher levels of happiness. These effects are stronger in the upper quantile of depression and the median quantile of happiness.", "qid": 12, "docid": "2pcc8dmt", "rank": 56, "score": 7.627999782562256}, {"content": "Title: Rapid Implementation of Inpatient Telepalliative Medicine Consultations During COVID-19 Pandemic Content: As coronavirus disease 2019 cases increase throughout the country and health care systems grapple with the need to decrease provider exposure and minimize personal protective equipment use while maintaining high-quality patient care, our specialty is called on to consider new methods of delivering inpatient palliative care (PC). Telepalliative medicine has been used to great effect in outpatient and home-based PC but has had fewer applications in the inpatient setting. As we plan for decreased provider availability because of quarantine and redeployment and seek to reach increasingly isolated hospitalized patients in the face of coronavirus disease 2019, the need for telepalliative medicine in the inpatient setting is now clear. We describe our rapid and ongoing implementation of telepalliative medicine consultation for our inpatient PC teams and discuss lessons learned and recommendations for programs considering similar care models.", "qid": 12, "docid": "mucsf9op", "rank": 57, "score": 7.623700141906738}, {"content": "Title: Hygiene: new hopes, new horizons Content: Summary Although promotion of safe hygiene is the single most cost-effective means of preventing infectious disease, investment in hygiene is low both in the health and in the water and sanitation sectors. Evidence shows the benefit of improved hygiene, especially for improved handwashing and safe stool disposal. A growing understanding of what drives hygiene behaviour and creative partnerships are providing fresh approaches to change behaviour. However, some important gaps in our knowledge exist. For example, almost no trials of the effectiveness of interventions to improve food hygiene in developing countries are available. We also need to figure out how best to make safe hygiene practices matters of daily routine that are sustained by social norms on a mass scale. Full and active involvement of the health sector in getting safe hygiene to all homes, schools, and institutions will bring major gains to public health.", "qid": 12, "docid": "x7s6ahy6", "rank": 58, "score": 7.611700057983398}, {"content": "Title: Optimizing your telemedicine visit during the COVID\u201019 pandemic: Practice guidelines for patients with head and neck cancer Content: The COVID\u201019 epidemic has resulted in many hospitals and practices to cancel in\u2010person outpatient clinic visits, where head and neck patients receive their critical longitudinal care. Out of necessity, most practices have been encouraged to use telemedicine as a method to maintain a continuum of care with their patients. As a result, the prevalence of telemedicine has grown rapidly during this pandemic, without allowing the physicians and patients to be adequately educated on how best to utilize the services. There is a steep learning curve as we have learned, and our goal is to provide guidelines for both patients and physicians, as well as a valuable patient handout in preparation for their visit.", "qid": 12, "docid": "njlo6g78", "rank": 59, "score": 7.578800201416016}, {"content": "Title: Optimizing your telemedicine visit during the COVID-19 pandemic: Practice guidelines for patients with head and neck cancer Content: The COVID-19 epidemic has resulted in many hospitals and practices to cancel in-person outpatient clinic visits, where head and neck patients receive their critical longitudinal care. Out of necessity, most practices have been encouraged to use telemedicine as a method to maintain a continuum of care with their patients. As a result, the prevalence of telemedicine has grown rapidly during this pandemic, without allowing the physicians and patients to be adequately educated on how best to utilize the services. There is a steep learning curve as we have learned, and our goal is to provide guidelines for both patients and physicians, as well as a valuable patient handout in preparation for their visit.", "qid": 12, "docid": "tcvm715u", "rank": 60, "score": 7.578799247741699}, {"content": "Title: Biologics increase the risk of SARS\u2010CoV\u20102 infection and hospitalization, but not ICU admission and death: Real\u2010life data from a large cohort during red\u2010zone declaration Content: During COVID\u201019 outbreak there are discordant opinions toward the impact on biologics in psoriatic (PsO) patients. Thus we performed a single\u2010center case\u2010control study in Lombardia, the Italian region with the higher number of COVID\u201019 confirmed cases. We enrolled 1193 PsO patients treated with biologics and small molecules and we used the entire Lombardia population as controls. Notably, 17 PsO patients COVID\u201019 confirmed were quarantined at home and five hospitalized, no PsO patients were admitted to intensive care unit (ICU) or died. With respect to the general population of Lombardy, patients on biologics were at higher risk to test positive for COVID\u201019 (odds ratio [OR] 3.43 [95% confidence interval (CI) 2.25\u20105.73], P < .0001), to be self\u2010quarantined at home (OR 9.05 [95% CI 5.61\u201014.61], P < .0001) and hospitalized (OR 3.59 [95% CI 1.49\u20108.63], P = .0044), however, not increased risk of ICU admission or death were found. PsO patients on biologics should be carefully monitored with telemedicine during COVID\u201019 outbreak and early treated at home to limit hospital overwhelm.", "qid": 12, "docid": "vb9ks4mq", "rank": 61, "score": 7.573299884796143}, {"content": "Title: Biologics increase the risk of SARS-CoV-2 infection and hospitalization, but not ICU admission and death: Real-life data from a large cohort during red-zone declaration Content: During COVID-19 outbreak there are discordant opinions toward the impact of biologics in psoriatic (PsO) patients. Thus we performed a single-center case-control study in Lombardia, the Italian region with the higher number of COVID-19 confirmed cases. We enrolled 1193 PsO patients treated with biologics and small molecules and we used the entire Lombardia population as controls. Notably, 17 PsO patients COVID-19 confirmed were quarantined at home and five hospitalized, no PsO patients were admitted to intensive care unit (ICU) or died. With respect to the general population of Lombardy, patients on biologics were at higher risk to test positive for COVID-19 (odds ratio [OR] 3.43 [95% confidence interval (CI) 2.25-5.73], P < .0001), to be self-quarantined at home (OR 9.05 [95% CI 5.61-14.61], P < .0001) and hospitalized (OR 3.59 [95% CI 1.49-8.63], P = .0044), however, not increased risk of ICU admission or death were found. PsO patients on biologics should be carefully monitored with telemedicine during COVID-19 outbreak and early treated at home to limit hospital overwhelm.", "qid": 12, "docid": "y84qrr2x", "rank": 62, "score": 7.573298931121826}, {"content": "Title: Practical measures to prevent COVID-19: A mini-review Content: In view of the global COVID-19 pandemic, this study focuses on the most up-to-date epidemiology, transmission, clinical manifestations, effective management, prevention and maintaining social distancing worldwide. The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease was first reported from Wuhan, China, in December, 2019. Till now this pandemic had spread to 209 countries and territories around the world and 2 international conveyances with 1,455,519 confirmed cases, including 83,664 deaths, as of April 08, 2020, so the World Health Organization declared it as a Public Health Emergency of worldwide (https://www.worldometers.info/coronavirus/). The main clinical manifestations are included fever, coughing, sore throat, fatigue, headache, diarrhea, hemoptysis, trouble breathing, blue lips or face, persistent pain or pressure in the chest, confusion and excessive drowsiness. Preventive measures such as; masks, frequent hand washing, staying at home, avoid public contact and quarantines are being recommended for reducing the transmission. To date, no specific antiviral treatment is proven yet. The countries with a high risk of infection, they need proper awareness and management for good protection.", "qid": 12, "docid": "wyliojb7", "rank": 63, "score": 7.567599773406982}, {"content": "Title: Efficiency of quarantine during an epidemic of severe acute respiratory syndrome--Beijing, China, 2003. Content: During March--July 2003, an epidemic of severe acute respiratory syndrome (SARS) in Beijing, China, accounted for 2,521 probable cases (attack rate: 19 per 100,000 population). To control the epidemic, public health officials initiated enhanced surveillance, isolation of SARS patients, use of personal protective equipment (PPE) by health-care workers, and quarantine of contacts of known SARS patients. Approximately 30,000 Beijing residents were quarantined in their homes or quarantine sites. To guide future quarantine policy, the Chinese Field Epidemiology Training Program (China FETP) of the Chinese Center for Disease Control and Prevention (China CDC) conducted a survey to estimate the risk for acquiring SARS among quarantined residents of Haidian District (2001 population: 2.24 million), Beijing, in May 2003, 1 month after the epidemic peaked. This report summarizes the results of that survey, which indicate that, as a component of a comprehensive SARS-control program, quarantine should be limited to persons who have contact with an actively ill SARS patient in the home or hospital, allowing for better focus of resources in future outbreaks.", "qid": 12, "docid": "2nqava5a", "rank": 64, "score": 7.561200141906738}, {"content": "Title: Quantifying the effects of quarantine using an IBM SEIR model on scalefree networks Content: The COVID-19 pandemic led several countries to resort to social distancing, the only known way to slow down the spread of the virus and keep the health system under control. Here we use an individual based model (IBM) to study how the duration, start date and intensity of quarantine affect the height and position of the peak of the infection curve. We show that stochastic effects, inherent to the model dynamics, lead to variable outcomes for the same set of parameters, making it crucial to compute the probability of each result. To simplify the analysis we divide the outcomes in only two categories, that we call best and worst scenarios. Although long and intense quarantine is the best way to end the epidemic, it is very hard to implement in practice. Here we show that relatively short and intense quarantine periods can also be very effective in flattening the infection curve and even killing the virus, but the likelihood of such outcomes are low. Long quarantines of relatively low intensity, on the other hand, can delay the infection peak and reduce its size considerably with more than 50% probability, being a more effective policy than complete lockdown for short periods.", "qid": 12, "docid": "ofccakya", "rank": 65, "score": 7.530700206756592}, {"content": "Title: Rapid Implementation of Inpatient Telepalliative Medicine Consultations during COVID-19 Pandemic Content: Abstract As COVID-19 cases increase throughout the country and healthcare systems grapple with the need to decrease provider exposure and minimize personal protective equipment (PPE) use while maintaining high quality patient care, our specialty is called upon to consider new methods of delivering inpatient palliative care. Telepalliative medicine has been used to great effect in outpatient and home-based palliative care, but has had fewer applications in the inpatient setting. As we plan for decreased provider availability due to quarantine and redeployment and seek to reach increasingly isolated hospitalized patients in the face of COVID-19, the need for telepalliative medicine in the inpatient setting is now clear. We describe our rapid and ongoing implementation of telepalliative medicine consultation for our inpatient palliative care teams and discuss lessons learned and recommendations for programs considering similar care models.", "qid": 12, "docid": "kjx03hju", "rank": 66, "score": 7.527200222015381}, {"content": "Title: Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. Content: OBJECTIVE To determine what risk factors, other than genetic predisposition, contribute to the incidence of feline infectious peritonitis (FIP) in private breeding catteries and animal shelters. DESIGN Cats from 7 catteries and a shelter were observed monthly for 1 year. At each visit, cats were examined, fecal samples were collected for determination of feline coronavirus shedding, and blood samples were collected for determination of coronavirus antibody titers. Diagnostic tests were performed on all cats that died of FIP. ANIMALS 275 purebred or random-bred cats that were kept by private breeder-owners in homes. RESULTS 24 cats died of FIP during the study. Development of FIP was not associated with cattery, mean cat number, mean age, sex, cattery median coronavirus antibody titer, husbandry and quarantine practices, caging and breeding practices, or prevalence of concurrent diseases. However, risk factors for FIP included individual cat age individual cat coronavirus titer, overall frequency of fecal coronarvirus shedding, and the proportion of cats in the cattery that were chronic coronavirus shedders. Deaths from FIP were more frequent in fall and winter, and on the basis of analysis of cattery records, the number of deaths varied yearly. Epidemics (> 10% mortality rate) were reported at least once in 5 years in 4 catteries. CLINICAL IMPLICATIONS Elimination of FIP from a cattery is only possible by total elimination of endemic feline enteric coronavirus (FECV) infection. The most important procedure to reduce FECV from catteries is elimination of chronic FECV shedders.", "qid": 12, "docid": "srxjkp0v", "rank": 67, "score": 7.48799991607666}, {"content": "Title: Development of an interactive, agent-based local stochastic model of COVID-19 transmission and evaluation of mitigation strategies illustrated for the state of Massachusetts, USA Content: Since its discovery in the Hubei province of China, the global spread of the novel coronavirus SARS-CoV-2 has resulted in millions of COVID-19 cases and hundreds of thousands of deaths. The spread throughout Asia, Europe, and the Americas has presented one of the greatest infectious disease threats in recent history and has tested the capacity of global health infrastructures. Since no effective vaccine is available, isolation techniques to prevent infection such as home quarantine and social distancing while in public have remained the cornerstone of public health interventions. While government and health officials were charged with implementing stay-at-home strategies, many of which had little guidance as to the consequences of how quickly to begin them. Moreover, as the local epidemic curves have been flattened, the same officials must wrestle with when to ease or cease such restrictions as to not impose economic turmoil. To evaluate the effects of quarantine strategies during the initial epidemic, an agent based modeling framework was created to take into account local spread based on geographic and population data with a corresponding interactive desktop and web-based application. Using the state of Massachusetts in the United States of America, we have illustrated the consequences of implementing quarantines at different time points after the initial seeding of the state with COVID-19 cases. Furthermore, we suggest that this application can be adapted to other states, small countries, or regions within a country to provide decision makers with critical information necessary to best protect human health.", "qid": 12, "docid": "mdpyzr7c", "rank": 68, "score": 7.454100131988525}, {"content": "Title: Working from home in medicine during coronavirus: What equipment do you need to get started and what can you do to help from home? Content: The COVID-19 pandemic looks set to significantly change how we practice medicine. It is vital that the vulnerable and immunocompromised members of our workforce are protected, which may mean that they do not go into clinical areas. While the medical field has been slower than many professional areas to catch on to working from home, many trusts are already moving towards telephone or video outpatient appointments during COVID-19. We describe the equipment needed to set up working from home for healthcare practitioners (HCPs) and discuss a variety of other opportunities for home-based HCPs, including teaching, learning, carrying out audit and quality improvement work and offering psychological support for colleagues working on the front line.", "qid": 12, "docid": "2j591gq0", "rank": 69, "score": 7.436600208282471}, {"content": "Title: Acute Stroke Care in the Coronavirus Disease 2019 Pandemic Content: Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with serious public health risk and has taken the world off-guard with its rapid spread. As the COVID-19 pandemic intensifies, overwhelming the healthcare system and the medical community, current practice for the management of acute ischemic stroke (AIS) will require modification, and guidelines should be relaxed while maintaining high standard quality of care. The aim of these suggestions is to avoid contributing to the rapid spread of COVID-19 as well as to conserve what are likely to be very limited resources (including personnel, intensive care/hospital beds as well as physicians) while maintaining high quality care for patients with AIS. We present our recommendations for the management of acute stroke during the COVID-19 pandemics.", "qid": 12, "docid": "lpy7mh95", "rank": 70, "score": 7.422299861907959}, {"content": "Title: Ensuring mental health care during the SARS-CoV-2 epidemic in France: a narrative review Content: Abstract Objective: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. Methods: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. Results: We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: 1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; 2) age (the elderly form the population most vulnerable to the coronavirus); 3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and 4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of \"COVID+ units\". These units are under the dual supervision of a psychiatrist and an internist / infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. Discussion: French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.", "qid": 12, "docid": "w8oixzdg", "rank": 71, "score": 7.415900230407715}, {"content": "Title: The Impact of Hospital Visiting Hour Policies on Pediatric and Adult Patients and their Visitors. Content: BACKGROUND Policies concerning restricted or open visiting hours are being challenged in health care institutions internationally, with no apparent consensus on the appropriateness of the visiting hour policies for pediatric and adult patients. The rules that govern practice are often based on the institutional precedent and assumptions of staff, and may have little or no evidence to support them. Policy and practice related to visiting hours is of pressing concern in Canada, and in Ontario specifically, following the reaction to the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 and subsequent changes in visiting policies in most health care settings. A systematic investigation of the impact of hospital visiting hours on visitors (including patients, families, and significant others) would inform decision-makers who are responsible for hospital policies about the best available evidence. OBJECTIVES The objective of this review was to appraise and synthesize the best available evidence on the impact of hospital visiting hours on patients and their visitors. INCLUSION CRITERIA Types of participants This review considered studies that included both pediatric and adult hospital patients and their visitors. Participants were either patients, visitors, or health care providers in the following hospital settings: medical/surgical units, critical care (ICU, CCU, NICU), pediatrics, maternity, or general hospital wards.Articles were excluded if participants came from the following settings: post-operative and post-anaesthesia care units (PACU), dementia wards, long-term care settings or retirement homes, or delivery rooms. PACUs were excluded because there are aspects of the presence of visitors to these units that are very specific, and differ from the general visits to patients who are not in the immediate post-operative stage. Dementia wards, long-term care settings and retirement homes were excluded because these were considered to be their \"home\", so visiting would be quite different from that on acute care hospital wards. Finally, delivery rooms were excluded because this review does not evaluate the impact of the outcomes of presence during \"delivery\" (or other \"procedures\").Types of interventions Studies were considered for inclusion in this review if they evaluated the effect or impact of visiting policies. This included interventions targeted at limiting or expanding patient visiting. We anticipated a paucity of experimental studies regarding this review question, thus included observational studies where the impact of visiting policy on patients and/or visitors was a focus, but testing intervention(s) may not have been the primary aim. We did not consider observational studies that focused only on the presence of visitors during specific procedures, resuscitation, or childbirth. The reason is that this limited aspect of the presence of a significant other was not considered \"visiting\" per se, and would be best examined in another systematic review.Types of outcome measures For this review, outcome measures related to both patients and visitors as a result of visiting hour policies were considered, including but not limited to: patient and/or visitor satisfaction; attitudes; beliefs; perceptions; mood; or patient physiological outcomes. These also included health care provider beliefs, perceptions, and attitudes about the impact of visiting policies on patients and/or visitors. Studies were excluded if they examined the trend of current visiting hour policies (with no evaluation of their impact), or if they focused on visitor presence only during emergency procedures, resuscitation, or childbirth.Types of studies Randomized controlled trials (RCTs) or quasi-experimental studies were included. However, given the expected scarcity of these designs relevant to our review question, other quantitative research designs were considered, such as non-randomized controlled trials, before-and-after studies, and descriptive/observational studies. SEARCH STRATEGY Using a defined search and retrieval method the following databases from 1995-2007 were accessed: Medline, CINAHL, Embase, PsycINFO, HealthSTAR, Cochrane Database of Systematic Reviews, AMED, and ERIC. METHODOLOGICAL QUALITY Each paper was assessed by two independent reviewers for methodological quality prior to inclusion in the review using standardized critical appraisal instruments for evidence of effectiveness, from the Joanna Briggs Institute. Disagreements were dealt with by consultations with a third reviewer. DATA COLLECTION Information was extracted from each paper independently by two reviewers using the standardized data extraction tool developed by the Joanna Briggs Institute. Disagreements were dealt with by consultations with a third reviewer. DATA SYNTHESIS Due to type of designs and quality of available studies, it was not possible to pool quantitative research study results in a statistical meta-analysis. Since statistical pooling was not possible, the findings are presented in a descriptive narrative form. RESULTS Fifteen studies met the inclusion criteria for this review. The study designs were varied, and included one pilot randomized trial, two quasi-experimental studies, eight descriptive studies/cross-sectional surveys, and four pre-post intervention questionnaires. Findings were inconsistent across studies. Nurses inconsistently enforced visiting policies. In ICU settings, liberalized visiting hours did not increase septic complications. One study reinforced the need for increased patient control over visiting (individual visit contracts, devices). Flexible (open) visitation policies increased patient and visitor satisfaction, and sibling visitation was beneficial to the patient and family. In maternity settings, a 'combination policy' was useful (open visiting for partner, more restricted visiting for others). CONCLUSION Key recommendations are provided that refer to clinical practice in critical care, maternity, and general ward settings, as well as recommendations for future research. In critical care settings, policy makers/administrators need to be aware of their staff nurses' beliefs and attitudes about visiting policies, educate them about the rationale for these policies and consider program development to assist nurses to work with families. Open visitation, and ways to increase patient control of visiting should be considered. No connection was found between liberal visiting hours and increased infection rates. When facilitating sibling visitation in the NICU, a pre-visit education process is recommended. Maternity settings may wish to consider a 'combination' policy, where the women's partners and/or significant other would have open visiting (all day), with restricted visiting for others. In other general hospital ward settings, open visiting with a 'quiet hour' is suggested.", "qid": 12, "docid": "zu7i1et3", "rank": 72, "score": 7.411200046539307}, {"content": "Title: COVID19 REAL-WORLD DATA FOR THE US AND LESSONS TO RE-OPEN BUSINESSRevisedMEDRXIV/2020/109538 Content: In March of 2020, the COVID19 pandemic had expanded to the United States of America (US). Companies designated as essential for the US had to maintain productivity in spite of the growing threat created by the SARS-CoV-2 virus. With this report, we present the response of one such company, the Lennar Corporation, a major homebuilder in the US. Within days, Lennar had implemented a morning health check via its enterprise resource planning system , to identify associates (employees) who were sick, or not in their usual state of health. With this survey, Lennar was able to ensure that no one sick would show up to work, and instead, would self-quarantine at home. Furthermore, with thorough contact tracking, associates exposed to COVID19 patients (suspected or RT-PCR test-confirmed), were also asked to self-quarantine. This survey, in addition to other safety measures, such as an overhaul of the company with nearly 50% of the company working from home, prolific communication, and many more measures, Lennar was able to function safely for its associates and successfully as an enterprise. The data that we present here are real world data collected in the context of working throughout a dreadful pandemic, and the lessons learned could be helpful to other companies that are preparing to return to work.", "qid": 12, "docid": "xxbnu979", "rank": 73, "score": 7.407100200653076}, {"content": "Title: COVID\u201019 and hypertension\u2014evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID\u201019). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin\u2010angiotensin system (RAS) inhibitors due to a key role of angiotensin\u2010converting enzyme 2 receptors in the entry of the SARS\u2010CoV\u20102 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS\u2010CoV\u20102 virus infection or worsens the course of COVID\u201019. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID\u201019 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N\u2010terminal pro\u2010B\u2010type natriuretic peptide, D\u2010dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID\u201019 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well\u2010being. For the ongoing management of patients with hypertension, telemedicine\u2010based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID\u201019 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 12, "docid": "254z62e4", "rank": 74, "score": 7.406599998474121}, {"content": "Title: COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 12, "docid": "jhkc8of3", "rank": 75, "score": 7.406599044799805}, {"content": "Title: Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary Content: Staying at home for the prevention of Covid-19 virus is an accepted fact for everyone. Office workers are a group of people, who had to wake up early in the morning and at least had a fixed pattern of sleeping and working. In this situation, complaints about neck, shoulder and lower back tend to increase and this is a good time to learn and do some practical exercise at home. This letter presents some of the home-based exercise notes for prevention of musculoskeletal disorders among office workers, following the guidelines prepared by American College of Sports Medicine.", "qid": 12, "docid": "sj4ohk38", "rank": 76, "score": 7.3516998291015625}, {"content": "Title: Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary. Content: Staying at home for the prevention of Covid-19 virus is an accepted fact for everyone. Office workers are a group of people, who had to wake up early in the morning and at least had a fixed pattern of sleeping and working. In this situation, complaints about neck, shoulder and lower back tend to increase and this is a good time to learn and do some practical exercise at home. This letter presents some of the home-based exercise notes for prevention of musculoskeletal disorders among office workers, following the guidelines prepared by American College of Sports Medicine.", "qid": 12, "docid": "tg02icy0", "rank": 77, "score": 7.351698875427246}, {"content": "Title: Acute Stroke Care in the Coronavirus Disease 2019 Pandemic Content: Abstract Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with serious public health risk, and has taken the world off guard with its rapid spread. As the COVID-19 pandemic intensifies, overwhelming the healthcare system and the medical community, current practice for the management of acute ischemic stroke (AIS) will require modification, and guidelines should be relaxed while maintaining high standard quality of care. The aim of these suggestions is to avoid contributing to the rapid spread of COVID-19 as well as to conserve what are likely to be very limited resources (including personnel, intensive care/hospital beds as well as physicians) while maintain high quality care for patients with AIS. We present our recommendations for the management of acute stroke during the COVID-19 pandemics.", "qid": 12, "docid": "sroy543x", "rank": 78, "score": 7.3379998207092285}, {"content": "Title: Variability and limitations in home-based exercise program descriptions in oncology: a scoping review. Content: BACKGROUND The literature reflects considerable heterogeneity in what constitutes home-based exercise interventions. The variability for where and what \"home-based\" exercise can represent challenges interpretation of findings and appropriate advocacy, referral, or development of these models of care. Therefore, the objective of this review was to provide a comprehensive summary of how home-based exercise is defined and reported in the literature and summarize the range of supportive elements utilized in home-based exercise trials. METHODS We followed methodology for scoping reviews. Relevant research databases were searched from inception to March 2019. Two reviewers independently screened articles to determine eligibility and extracted terminology used to describe home-based exercise and intervention details for intervention delivery. RESULTS Of the 9432 records identified, 229 articles met inclusion criteria. Across the literature, exercise interventions were described as home-based if they were completed at-home, outdoors in the neighbourhood, and in community facilities; or in self-selected environments; or if they were unsupervised. Supportive elements for home-based models ranged with respect to the amount of supervision and resources utilized, including the provision of print materials, exercise equipment, telephone support, home visits, and technology. CONCLUSIONS This review provides a comprehensive summary of strategies previously utilized to deliver home-based exercise interventions in oncology, along with the various definitions of the home-based environment for exercise reported by researchers. Specific recommendations to improve the prescription and reporting of home-based exercise interventions are provided in order to facilitate the delivery, evaluation, and translation of findings into clinical practice.", "qid": 12, "docid": "3gsczkua", "rank": 79, "score": 7.337600231170654}, {"content": "Title: Control of Severe Acute Respiratory Syndrome in Singapore Content: A Severe Acute Respiratory Syndrome (SARS) outbreak occurred in Singapore from February to May 2003. A high vigilance for the disease, frequent and regular temperature monitoring, early case identification and isolation of patients, as well as tracing and home quarantine of contacts, played major roles in controlling the outbreak. Hospitals were dedicated to the screening and treatment of SARS patients. Within and between hospitals, movement by healthcare workers, patients and visitors were restricted, as was the number of hospital visitors. Staff education and audits of infection control practices also featured prominently. To prevent cross-border transmission, incoming travellers from SARS affected areas had to complete health declaration cards. They, as well as all outgoing travellers from Singapore, were monitored for fever. In the meantime, the public was urged to refrain from travelling to SARS affected regions. Containment elements targeting the community included school closure, public education on good hygiene and readily accessible public information. In response to a laboratory acquired SARS infection, laboratories were audited, and directives issued on the mandatory use of biosafety level 3 laboratories for SARS virus culture, and compliance of laboratory workers to biosafety guidelines.", "qid": 12, "docid": "zwjiv8lm", "rank": 80, "score": 7.337399959564209}, {"content": "Title: Canadian Society of Nephrology COVID-19 Rapid Response Team Home Dialysis Recommendations Content: PURPOSE OF PROGRAM: This paper will provide guidance on how to best manage patients with end-stage kidney disease who will be or are being treated with home dialysis during the COVID-19 pandemic. SOURCES OF INFORMATION: Program-specific documents, pre-existing, and related to COVID-19; documents from national and international kidney agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature. METHODS: Members of the Canadian Society of Nephrology (CSN) Board of Directors solicited a team of clinicians and administrators with expertise in home dialysis. Specific COVID-19-related themes in home dialysis were determined by the Canadian senior renal leaders community of practice, a group compromising medical and administrative leaders of provincial and health authority renal programs. We then developed consensus-based recommendations virtually by the CSN work-group with input from ethicists with nephrology training. The recommendations were further reviewed by community nephrologists and over a CSN-sponsored webinar, attended by 225 kidney health care professionals, for further peer input. The final consensus recommendations also incorporated review by the editors at the Canadian Journal of Kidney Health and Disease (CJKHD). KEY FINDINGS: We identified 7 broad areas of home dialysis practice management that may be affected by the COVID-19 pandemic: (1) peritoneal dialysis catheter placement, (2) home dialysis training, (3) home dialysis management, (4) personal protective equipment, (5) product delivery, (6) minimizing direct health care provider and patient contact, and (7) assisted peritoneal dialysis in the community. We make specific suggestions and recommendations for each of these areas. LIMITATIONS: This suggestions and recommendations in this paper are expert opinion, and subject to the biases associated with this level of evidence. To expedite the publication of this work, a parallel review process was created that may not be as robust as standard arms\u2019 length peer-review processes. IMPLICATIONS: These recommendations are intended to provide the best care possible during a time of altered priorities and reduced resources.", "qid": 12, "docid": "jq1p5t8w", "rank": 81, "score": 7.313600063323975}, {"content": "Title: Perioperative fluid therapy: a statement from the international Fluid Optimization Group. Content: BACKGROUND Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered. METHODS Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them. RESULTS The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration. CONCLUSIONS We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.", "qid": 12, "docid": "e7xymovf", "rank": 82, "score": 7.309000015258789}, {"content": "Title: COVID-19 Pandemic: What Every Otolaryngologist-Head and Neck Surgeon Needs to Know for Safe Airway Management Content: The novel coronavirus disease 2019 (COVID-19) pandemic has unfolded with remarkable speed, posing unprecedented challenges for health care systems and society. Otolaryngologists have a special role in responding to this crisis by virtue of expertise in airway management. Against the backdrop of nations struggling to contain the virus's spread and to manage hospital strain, otolaryngologists must partner with anesthesiologists and front-line health care teams to provide expert services in high-risk situations while reducing transmission. Airway management and airway endoscopy, whether awake or sedated, expose operators to infectious aerosols, posing risks to staff. This commentary provides background on the outbreak, highlights critical considerations around mitigating infectious aerosol contact, and outlines best practices for airway-related clinical decision making during the COVID-19 pandemic. What otolaryngologists need to know and what actions are required are considered alongside the implications of increasing demand for tracheostomy. Approaches to managing the airway are presented, emphasizing safety of patients and the health care team.", "qid": 12, "docid": "6mzv33vv", "rank": 83, "score": 7.297599792480469}, {"content": "Title: COVID-19 Pandemic: What Every Otolaryngologist-Head and Neck Surgeon Needs to Know for Safe Airway Management. Content: The novel coronavirus disease 2019 (COVID-19) pandemic has unfolded with remarkable speed, posing unprecedented challenges for health care systems and society. Otolaryngologists have a special role in responding to this crisis by virtue of expertise in airway management. Against the backdrop of nations struggling to contain the virus's spread and to manage hospital strain, otolaryngologists must partner with anesthesiologists and front-line health care teams to provide expert services in high-risk situations while reducing transmission. Airway management and airway endoscopy, whether awake or sedated, expose operators to infectious aerosols, posing risks to staff. This commentary provides background on the outbreak, highlights critical considerations around mitigating infectious aerosol contact, and outlines best practices for airway-related clinical decision making during the COVID-19 pandemic. What otolaryngologists need to know and what actions are required are considered alongside the implications of increasing demand for tracheostomy. Approaches to managing the airway are presented, emphasizing safety of patients and the health care team.", "qid": 12, "docid": "deuqg5ud", "rank": 84, "score": 7.297598838806152}, {"content": "Title: Projection of hospitalization by COVID-19 in Brazilfollowing different social distances policies Content: Following the first infections in the Wuhan City, COVID-19 became a global pandemic as declared by the World Health Organization (WHO). Since it is an airborne disease transmitted between humans, many countries adopted a quarantine on their own population as well as closing borders measures. In Brazil many are discussing the best way to manage the opening of the quarantine under the constraints of hospitals infrastructure. In this work we implement a forecast of the demand for hospital beds for the next 30 days for every state in Brazil for different quarantine flexibilization scenarios and analyse how long it would take for the demand to exceed current available hospital beds.", "qid": 12, "docid": "obehsz2z", "rank": 85, "score": 7.291600227355957}, {"content": "Title: The experience of quarantine for individuals affected by SARS in Toronto. Content: OBJECTIVE The purpose of this study was to explore the experience of home quarantine during the severe acute respiratory syndrome (SARS) outbreak in Toronto in 2003. DESIGN Qualitative descriptive design. SAMPLE Stratified random sampling techniques were used to generate a list of potential participants, who varied in terms of gender and closeness of exposure to someone with suspected SARS (contact level). Twenty-one individuals participated in the study. MEASUREMENTS All interviews were audiotaped and followed a semistructured interview guide. Participants were invited to describe their experience of quarantine in detail including their advice for Public Health. RESULTS The experience followed a trajectory of stages beginning before quarantine and ending after quarantine. Despite individual differences, common themes of uncertainty, isolation, and coping intersected the data. CONCLUSIONS Public Health has a dual role of monitoring compliance and providing support to people in quarantine. This study has implications for public health policy and practice in planning for future public health emergencies in terms of the information and the resources required to mount an effective response.", "qid": 12, "docid": "xdgd11k6", "rank": 86, "score": 7.264999866485596}, {"content": "Title: Systems modeling in support of evidence-based disaster planning for rural areas Content: Abstract The objective of this communication is to introduce a conceptual framework for a study that applies a rigorous systems approach to rural disaster preparedness and planning. System Dynamics is a well-established computer-based simulation modeling methodology for analyzing complex social systems that are difficult to change and predict. This approach has been applied for decades to a wide variety of issues of healthcare and other types of service capacity and delivery, and more recently, to some issues of disaster planning and mitigation. The study will use the System Dynamics approach to create computer simulation models as \u201cwhat-if\u201d tools for disaster preparedness planners. We have recently applied the approach to the issue of hospital surge capacity, and have reached some preliminary conclusions \u2013 for example, on the question of where in the hospital to place supplementary nursing staff during a severe infectious disease outbreak\u2014some of which we had not expected. Other hospital disaster preparedness issues well suited to System Dynamics analysis include sustaining employee competence and reducing turnover, coordination of medical care and public health resources, and hospital coordination with the wider community to address mass casualties. The approach may also be applied to preparedness issues for agencies other than hospitals, and could help to improve the interactions among all agencies represented in a community's local emergency planning committee. The simulation models will support an evidence-based approach to rural disaster planning, helping to tie empirical data to decision-making. Disaster planners will be able to simulate a wide variety of scenarios, learn responses to each and develop principles or best practices that apply to a broad spectrum of disaster scenarios. These skills and insights would improve public health practice and be of particular use in the promotion of injury and disease prevention programs and practices.", "qid": 12, "docid": "ij3faz52", "rank": 87, "score": 7.254899978637695}, {"content": "Title: Clinical Practice Update: Expert Review on Endoscopic Bariatric Therapies. Content: BACKGROUND & AIMS Multiple endoscopic bariatric therapies (EBTs) currently are being evaluated or are in clinical use in the United States. EBTs are well positioned to fill an important gap in the management of obesity and metabolic disease. The purpose of this expert review is to update gastroenterologists on these therapies and provide practice advice on how to incorporate them into clinical practice. METHODS The evidence reviewed in this work is a distillation of comprehensive search of several English-language databases and a manual review of relevant publications (including systematic reviews and meeting abstracts). Best Practice Advice 1: EBTs should be considered in patients with obesity who have been unsuccessful in losing or maintaining weight loss with lifestyle interventions. Best Practice Advice 2: EBTs can be used in patients with severe obesity as a bridge to traditional bariatric surgery. They also can be used as a bridge to allow unrelated interventions that are unable to be performed because of weight limits (ie, orthopedic surgery, organ transplantation). Best Practice Advice 3: Clinicians should use EBTs as part of a structured weight loss program that includes dietary intervention, exercise therapy, and behavior modification, in both the active weight loss phase and the long-term maintenance phase. Best Practice Advice 4: Clinicians should screen all potential EBT candidates with a comprehensive evaluation for medical conditions, comorbidities, and psychosocial or behavioral patterns that contribute to their condition before enrolling patients in a weight loss program that includes EBTs. Best Practice Advice 5: Clinicians incorporating EBTs into their clinical practice should follow up patients prospectively to capture the impact of the EBT program on weight and weight-related comorbidities, and all related adverse outcomes. Poor responders should be identified and offered a detailed evaluation and alternative therapy. Best Practice Advice 6: Clinicians embarking on incorporating EBTs into their clinical practice should have a comprehensive knowledge of the indications, contraindications, risks, benefits, and outcomes of individual EBTs, as well as a practical knowledge of the risks and benefits of alternative therapies for obesity. Best Practice Advice 7: Institutions should establish specific guidelines that are applied consistently across disciplines for granting privileges in EBTs that reflect the necessary knowledge and technical skill a clinician must achieve before being granted privileges to perform these procedures.", "qid": 12, "docid": "dlaoshff", "rank": 88, "score": 7.244900226593018}, {"content": "Title: Coping with diabetes during the COVID - 19 lockdown in India: Results of an online pilot survey Content: AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients.", "qid": 12, "docid": "1lfm24wz", "rank": 89, "score": 7.237400054931641}, {"content": "Title: Coping with diabetes during the COVID \u2013 19 lockdown in India: Results of an online pilot survey Content: AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients.", "qid": 12, "docid": "v8z5jyz2", "rank": 90, "score": 7.237399101257324}, {"content": "Title: Practice Management During the COVID-19 Pandemic Content: On March 14, 2020, the Surgeon General of the United States urged a widespread cessation of all elective surgery across the country. The suddenness of this mandate and the concomitant spread of the COVID-19 virus left many hospital systems, orthopaedic practices, and patients with notable anxiety and confusion as to the near, intermediate, and long-term future of our healthcare system. As with most businesses in the United States during this time, many orthopaedic practices have been emotionally and fiscally devastated because of this crisis. Furthermore, this pandemic is occurring at a time where small and midsized orthopaedic groups are already struggling to cover practice overhead and to maintain autonomy from larger health systems. It is anticipated that many groups will experience financial demise, leading to substantial global consolidation. Because the authors represent some of the larger musculoskeletal multispecialty groups in the country, we are uniquely positioned to provide a framework with recommendations to best weather the ensuing months. We think these recommendations will allow providers and their staff to return to an infrastructure that can adjust immediately to the pent-up healthcare demand that may occur after the COVID-19 pandemic. In this editorial, we address practice finances, staffing, telehealth, operational plans after the crisis, and ethical considerations.", "qid": 12, "docid": "l2mwdqw0", "rank": 91, "score": 7.224599838256836}, {"content": "Title: Identification of patient venous thromboembolism risk across the continuum of care. Content: Venous thromboembolism (VTE) complications are the leading cause of preventable in-hospital mortality and morbidity in the United States. Initiatives by the National Quality Forum, the Joint Commission, and the Surgical Care Improvement Project aim to improve the prevention of VTE and emphasize the need to recognize the risk of the condition in hospitalized patients. In clinical practice, individual risk assessment using a validated scoring system provides patients with the best care in the prevention of VTE. This is accomplished by a weighted scoring of risk factors, selection of the most appropriate prevention strategy for patients at risk, and regular risk review across the continuum of care. All hospitals should have a local, written, care pathway which assesses inpatient risk of VTE as early as possible upon admission and identifies members of the health care team responsible for applying risk assessment. Venous thromboembolism risk should be regularly reassessed for any changes in the level of risk, with extended out-of-hospital prophylaxis considered for patients with continued risk factors, such as prolonged immobility or illness, treated at home, or in a long-term care facility. Finally, a mandatory alert system requiring the clinician to address the issue of prophylaxis before any orders are carried out by the nursing staff is one way to protect all hospitalized patients.", "qid": 12, "docid": "evdvghkk", "rank": 92, "score": 7.154699802398682}, {"content": "Title: Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak Content: The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.", "qid": 12, "docid": "roa7l6c0", "rank": 93, "score": 7.145699977874756}, {"content": "Title: Scholar in the SEPR spotlight: Ian Douglas Content: In this reflective essay of intellectual autobiography, I respond to a series of questions the journal editor Wei-Ning Xiang asked about my 55-year journey from applied geography to socio-ecological practice research. These are (1) what and/or who had inspired your career most in geography and socio-ecological practice research? (2) Throughout your 55-year academic journey, did you ever reorient your ambitions in scholarly pursuit, or even reinvent yourself in your academic life? What motivated you in each of these instances? (3) How do you measure success in your work? Among many accomplishments, what are the top three that you are most proud of? (4) From your personal experience, what would be the most important attributes for a well-lived, fully realised, and meaningful life? Do you have any tips for maintaining work-life balance? (5) Do you have any specific advice for younger scholars in geography and socio-ecological practice research? (6) What are the three most interesting images reflecting turning points in your career? I hope that my experiences and insights showcased in this essay are helpful to the younger generations of geographers and socio-ecological practice researchers.", "qid": 12, "docid": "ymokohct", "rank": 94, "score": 7.123000144958496}, {"content": "Title: Forecasting the impact of the first wave of the COVID-19 pandemic on hospital demand and deaths for the USA and European Economic Area countries Content: Summary Background: Hospitals need to plan for the surge in demand in each state or region in the United States and the European Economic Area (EEA) due to the COVID-19 pandemic. Planners need forecasts of the most likely trajectory in the coming weeks and will want to plan for the higher values in the range of those forecasts. To date, forecasts of what is most likely to occur in the weeks ahead are not available for states in the USA or for all countries in the EEA. Methods: This study used data on confirmed COVID-19 deaths by day from local and national government websites and WHO. Data on hospital capacity and utilisation and observed COVID-19 utilisation data from select locations were obtained from publicly available sources and direct contributions of data from select local governments. We develop a mixed effects non-linear regression framework to estimate the trajectory of the cumulative and daily death rate as a function of the implementation of social distancing measures, supported by additional evidence from mobile phone data. An extended mixture model was used in data rich settings to capture asymmetric daily death patterns. Health service needs were forecast using a micro-simulation model that estimates hospital admissions, ICU admissions, length of stay, and ventilator need using available data on clinical practices in COVID-19 patients. We assume that those jurisdictions that have not implemented school closures, non-essential business closures, and stay at home orders will do so within twenty-one days. Findings: Compared to licensed capacity and average annual occupancy rates, excess demand in the USA from COVID-19 at the estimated peak of the epidemic (the end of the second week of April) is predicted to be 9,079 (95% UI 253-61,937) total beds and 9,356 (3,526-29,714) ICU beds. At the peak of the epidemic, ventilator use is predicted to be 16,545 (8,083-41,991). The corresponding numbers for EEA countries are 120,080 (119,183-121,107), 32,291 (32,157-32,425) and 28,973 (28,868-29,085) at a peak of April 6. The date of peak daily deaths varies from March 30 through May 12 by state in the USA and March 27 through May 4 by country in the EEA. We estimate that through the end of July, there will be 60,308 (34,063-140,381) deaths from COVID-19 in the USA and 143,088 (101,131-253,163) deaths in the EEA. Deaths from COVID-19 are estimated to drop below 0.3 per million between May 4 and June 29 by state in the USA and between May 4 and July 13 by country in the EEA. Timing of the peak need for hospital resource requirements varies considerably across states in the USA and across regions of Europe. Interpretation: In addition to a large number of deaths from COVID-19, the epidemic will place a load on health system resources well beyond the current capacity of hospitals in the USA and EEA to manage, especially for ICU care and ventilator use. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures within three weeks in all locations that have not done so already and maintenance of these measures throughout the epidemic, emphasising the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.", "qid": 12, "docid": "c1dy5vsn", "rank": 95, "score": 7.11959981918335}, {"content": "Title: Confronting COVID-19: Surging critical care capacity in Italy Content: The current spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Europe threats Italian capacity and that of other national health systems to effectively respond to the needs of patients who require intensive care, mostly due to pneumonia and derived complications from concomitant disease and age. Predicting the surge in capacity has proved difficult due to the requirement of a subtle combination of diverse expertise and difficult choices to be made on selecting robust measures of critical care utilization, and parsimonious epidemic modelling which account for changing government measures. We modelled the required surge capacity of ICU beds in Italy exclusively for COVID-19 patients at epidemic peak. Because new measures were imposed by the Italian government, suspending nearly all non-essential sectors of the economy, we included the potential impacts of these new measures. The modelling considered those hospitalized and home isolated as quarantined, mimicking conditions on the ground. The percentage of patients in intensive care (out of the daily active confirmed cases) required for our calculations were chosen based on clinical relevance and robustness, and this number was consistently on average 9.9% from February 24 to March 6, 2020. Five different scenarios were produced (two positive and three negative). Under most positive scenarios, in which R0 is reduced below 1 (i.e., 0.71), the number of daily active confirmed cases will peak at nearly 89 000 by the early days of April and the total number of intensive care beds exclusively dedicated to COVID-19 patients required in Italy estimated at 8791. Worst scenarios produce unmanageable numbers. Our results suggest that the decisive moment for Italy has come. Jointly reinforcement by the government of the measures approved so far, including home confinement, but even more important the full commitment of the civil society in respecting home confinement, social distancing and hygiene will be key in the next days. Yet, even under the best circumstances, intensive care capacity will need to get closer to 9000 units in the country to avoid preventable mortality. So far, only strong measures were effective in Italy, as shown by our modelling, and this may offer an opportunity to European countries to accelerate their interventions.", "qid": 12, "docid": "ehr9ae82", "rank": 96, "score": 7.10890007019043}, {"content": "Title: How to improve adherence with quarantine: Rapid review of the evidence Content: Abstract Objectives The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to \u2018self-isolate\u2019 if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design Rapid evidence review. Methods We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "9hrrkqgi", "rank": 97, "score": 7.102200031280518}, {"content": "Title: How to improve adherence with quarantine: rapid review of the evidence Content: OBJECTIVES: The December 2019 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to 'self-isolate' if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. STUDY DESIGN: The study design is a rapid evidence review. METHODS: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. RESULTS: We found 3163 articles and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. CONCLUSIONS: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "kjnnh00e", "rank": 98, "score": 7.102199077606201}, {"content": "Title: How to improve adherence with quarantine: Rapid review of the evidence Content: Objectives: The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to self-isolate if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design: Rapid evidence review. Methods: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results: We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "s0zdqd6d", "rank": 99, "score": 7.102198123931885}, {"content": "Title: [Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19]. Content: OBJECTIVE To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. METHODS Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method. RESULTS There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. CONCLUSIONS There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.", "qid": 12, "docid": "r5c68gj7", "rank": 100, "score": 7.1016998291015625}]}
{"query": "what are the transmission routes of coronavirus?", "hits": [{"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review Content: In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 13, "docid": "yyfuu197", "rank": 1, "score": 8.135899543762207}, {"content": "Title: Closing the knowledge gaps on MERS: three and half years since its detection, what have we learnt and what needs to be done urgently? (Editorial). Content: The Middle East respiratory syndrome coronavirus (MERS-Cov), first detected in 2012, continues to cause health concerns owing to the grave uncertainties that have surrounded the virus since it emerged. Three and half years after the first known human infection was detected, cases continue to be reported every month, over 85% of which have been from Saudi Arabia and other countries in the Arabian Peninsula. Despite its low levels of transmission, the virus presents an uncertain future as a number of critical knowledge gaps on the source and route of transmission have hindered the global response to this emerging infection.", "qid": 13, "docid": "g0qhgvv6", "rank": 2, "score": 7.79010009765625}, {"content": "Title: Facing the COVID\u201019 outbreak: What should we know and what could we do? Content: A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.", "qid": 13, "docid": "2ftw85xw", "rank": 3, "score": 7.783299922943115}, {"content": "Title: Tissue Distribution of the MERS-Coronavirus Receptor in Bats Content: Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.", "qid": 13, "docid": "3cxyogor", "rank": 4, "score": 7.653500080108643}, {"content": "Title: [Transmission routes of 2019-novel coronavirus (2019-nCoV)] Content: Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "qid": 13, "docid": "2yblpbwm", "rank": 5, "score": 7.235599994659424}, {"content": "Title: [Transmission routes of 2019-novel coronavirus (2019-nCoV)]. Content: Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "qid": 13, "docid": "85vnyr36", "rank": 6, "score": 7.235599040985107}, {"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen with Potential Fecal-Oral Transmission: A COVID-19 Virological and Clinical Review Content: Abstract In as short as 3 months, COVID-19 has spread and ravaged the world in an unprecedented speed in modern history rivaling the 1918 flu pandemic. SARS-CoV-2, the culprit virus, is highly contagious and stable in the environment and predominantly transmits among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that SARS-CoV-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 13, "docid": "9rg9xe57", "rank": 7, "score": 6.966700077056885}, {"content": "Title: Personal Protective Equipment and COVID-19: A Review for Surgeons Content: There is a long history of personal protective equipment (PPE) used by the surgeon to minimize the transmission of various pathogens. In the context of the present coronavirus disease 2019 pandemic there is significant controversy as to what forms of PPE are appropriate or adequate. This review aims to describe the pathogenic mechanism and route of spread of the causative virus, severe acute respiratory syndrome coronavirus, as it pertains to accumulated published data from experienced centers globally. The various forms of PPE that are both available and appropriate are addressed. There are options in the form of eyewear, gloves, masks, respirators, and gowns. The logical and practical utilization of these should be data driven and evolve based on both experience and data. Last, situations specific to surgical populations are addressed. We aim to provide granular collective data that has thus far been published and that can be used as a reference for optimal PPE choices in the perioperative setting for surgical teams.", "qid": 13, "docid": "5ekj7zsx", "rank": 8, "score": 6.878799915313721}, {"content": "Title: Personal Protective Equipment and COVID-19: A Review for Surgeons Content: : There is a long history of personal protective equipment (PPE) used by the surgeon to minimize the transmission of various pathogens. In the context of the present coronavirus disease 2019 pandemic there is significant controversy as to what forms of PPE are appropriate or adequate. This review aims to describe the pathogenic mechanism and route of spread of the causative virus, severe acute respiratory syndrome coronavirus, as it pertains to accumulated published data from experienced centers globally. The various forms of PPE that are both available and appropriate are addressed. There are options in the form of eyewear, gloves, masks, respirators, and gowns. The logical and practical utilization of these should be data driven and evolve based on both experience and data. Last, situations specific to surgical populations are addressed. We aim to provide granular collective data that has thus far been published and that can be used as a reference for optimal PPE choices in the perioperative setting for surgical teams.", "qid": 13, "docid": "7dxjqub6", "rank": 9, "score": 6.878798961639404}, {"content": "Title: Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong Content: The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.", "qid": 13, "docid": "8rfm0jxh", "rank": 10, "score": 6.872300148010254}, {"content": "Title: A study of the probable transmission routes of MERS\u2010CoV during the first hospital outbreak in the Republic of Korea Content: Infections caused by the Middle East respiratory syndrome coronavirus (MERS\u2010CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS\u2010CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi\u2010agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long\u2010range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi\u2010agent modeling framework. Least\u2010squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super\u2010spreader, our model simulations suggested that MERS\u2010CoV probably spread via the long\u2010range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long\u2010range airborne and close contact route.", "qid": 13, "docid": "4nd5wzrm", "rank": 11, "score": 6.870100021362305}, {"content": "Title: Transmission routes of 2019-nCoV and controls in dental practice Content: A novel \u03b2-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal\u2013oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "qid": 13, "docid": "lasv4e6a", "rank": 12, "score": 6.818900108337402}, {"content": "Title: Transmission routes of 2019-nCoV and controls in dental practice Content: A novel \u00df-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "qid": 13, "docid": "wywldhr0", "rank": 13, "score": 6.818899154663086}, {"content": "Title: Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses Content: Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in\u2010flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%\u201072%) in the in\u2010flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5\u2010121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%\u201023%), 29% (95% CI: 27%\u201031%), and 50% (95% CI: 48%\u201053%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%\u201087%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2\u201077.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.", "qid": 13, "docid": "sfa9d1ux", "rank": 14, "score": 6.797100067138672}, {"content": "Title: What was the primary mode of smallpox transmission? Implications for biodefense Content: The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, \u201crespiratory droplet\u201d transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.", "qid": 13, "docid": "ycxyn2a2", "rank": 15, "score": 6.754000186920166}, {"content": "Title: COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics Content: COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.", "qid": 13, "docid": "61ta81iy", "rank": 16, "score": 6.730599880218506}, {"content": "Title: Body fluids may contribute to human-to-human transmission of severe acute respiratory syndrome coronavirus 2: evidence and practical experience Content: BACKGROUND: In December 2019, an unbelievable outbreak of pneumonia associated with coronavirus was reported in the city of Wuhan, Hubei Province. This virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although much effort has been spent on clarifying the transmission route of SARS-CoV-2, but, very little evidence is available regarding the relationship between human body fluids and transmission of SARS-CoV-2 virus. Considerable evidence from hospital in Wuhan indicates that strict rules to avoid occupational exposure to patients\u2019 body fluids in healthcare settings, particularly among every medical staff, limited person-to-person transmission of nosocomial infections by direct or indirect contact. CONCLUSION: We tried to provide important information for understanding the possible transmission routes of SARS-CoV-2 via body fluids including bronchoalveolar-lavage, saliva, blood, urine, feces, sputum, tears, and semen in order to control coronavirus disease 2019 (COVID-19) occurrences.", "qid": 13, "docid": "0a5fccio", "rank": 17, "score": 6.53380012512207}, {"content": "Title: Transmission routes of SARS-CoV-2 and protective measures in dental clinics during the COVID-19 pandemic Content: RESULTS: The outbreak of coronavirus disease 2019 (COVID-19) has become a primary challenging public health issue for not only China but also the world On March 11, 2020, the World Health Organization declared that the pandemic of COVID-19 had become a public health emergency of global concern As of May 12, 2020 COVID-19 has been reported in over 180 countries/regions, with a total of 4,178,156 confirmed cases and over 280,000 deaths The risk of cross-infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be elevated between dental specialists and patients due to the peculiarity of dental practice Therefore, detailed and effective infection control measures are imminently needed to prevent nosocomial coronavirus infection This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics Classification schemes as well as color identification according to the results of the questionnaire survey and temperature measurement in precheck and triages are innovations proposed in this paper CLINICAL SIGNIFICANCE: This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics", "qid": 13, "docid": "au0sfe8g", "rank": 18, "score": 6.498000144958496}, {"content": "Title: Transmission routes of SARS-CoV-2 and protective measures in dental clinics during the COVID-19 pandemic. Content: RESULTS The outbreak of coronavirus disease 2019 (COVID-19) has become a primary challenging public health issue for not only China but also the world. On March 11, 2020, the World Health Organization declared that the pandemic of COVID-19 had become a public health emergency of global concern. As of May 12, 2020 COVID-19 has been reported in over 180 countries/regions, with a total of 4,178,156 confirmed cases and over 280,000 deaths. The risk of cross-infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be elevated between dental specialists and patients due to the peculiarity of dental practice. Therefore, detailed and effective infection control measures are imminently needed to prevent nosocomial coronavirus infection. This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics. Classification schemes as well as color identification according to the results of the questionnaire survey and temperature measurement in precheck and triages are innovations proposed in this paper. CLINICAL SIGNIFICANCE This paper, based on proven effective experience, relevant guidelines, and research, not only presents the fundamental knowledge about the name, etiologic characteristics, epidemiologic characteristics and clinical manifestations of COVID-19, transmission routes and risk points of SARS-CoV-2 in dental clinics but also provides recommended protective measures for dental professionals to interdict the transmission of SARS-CoV-2 in dental clinics.", "qid": 13, "docid": "jxi0mvbi", "rank": 19, "score": 6.49799919128418}, {"content": "Title: Controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention. Content: PURPOSE OF REVIEW Health agencies recommend transmission-based precautions, including contact, droplet and airborne precautions, to mitigate transmission of respiratory viruses in healthcare settings. There is particular controversy over the importance of aerosol transmission and whether airborne precautions should be recommended for some respiratory viruses. Here, we review the current recommendations of transmission-based precautions and the latest evidence on the aerosol transmission of respiratory viruses. RECENT FINDINGS Viral nucleic acids, and in some instances viable viruses, have been detected in aerosols in the air in healthcare settings for some respiratory viruses such as seasonal and avian influenza viruses, Middle East respiratory syndrome-coronavirus and respiratory syncytial virus. However, current evidences are yet to demonstrate that these viruses can effectively spread via airborne route between individuals, or whether preventive measures in airborne precautions would be effective. SUMMARY Studies that use transmission events as outcome to demonstrate human-to-human transmission over the aerosol route or quantitative measurement of infectious respiratory viruses in the air are needed to evaluate the infectiousness of respiratory viruses over the aerosol route. When a respiratory virus in concern only leads to disease with low severity, airborne precautions are not likely to be justified.", "qid": 13, "docid": "zhcghyw8", "rank": 20, "score": 6.48960018157959}, {"content": "Title: SARS\u2010CoV\u20102 possible contamination of genital area: implications for sexual and vertical transmission routes Content: The severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is responsible for a pandemic that is causing thousands of deaths worldwide. The virus can be transmitted from person to person, directly or indirectly, via the respiratory, oro\u2010fecal and probably sexual routes.(1) The eventual vertical transmission route is still poorly explored. However, mother\u2010to\u2010child SARS\u2010CoV\u20102 transmission through the placenta probably does not occur, or likely occurs very rarely.(2) All the studies conducted on COVID\u201019 pregnant women involved patients undergoing cesarean section, but the indications for such delivery modality were not clearly stated.", "qid": 13, "docid": "scptrala", "rank": 21, "score": 6.46120023727417}, {"content": "Title: Multi-route respiratory infection: when a transmission route may dominate Content: The exact transmission route of many respiratory infectious diseases remains a subject for debate to date. The relative contribution ratio of each transmission route is largely undetermined, which is affected by environmental conditions, human behavior, the host and the microorganism. In this study, a detailed mathematical model is developed to investigate the relative contributions of different transmission routes to a multi-route transmitted respiratory infection. It is illustrated that all transmission routes can dominate the total transmission risk under different scenarios. Influential parameters considered include dose-response rate of different routes, droplet governing size that determines virus content in droplets, exposure distance, and virus dose transported to the hand of infector. Our multi-route transmission model provides a comprehensive but straightforward method to evaluate the transmission efficiency of different transmission routes of respiratory diseases and provides a basis for predicting the impact of individual level intervention methods such as increasing close-contact distance and wearing protective masks.", "qid": 13, "docid": "mfnzkvd0", "rank": 22, "score": 6.454699993133545}, {"content": "Title: Novel analytic tools for the study of porcine reproductive and respiratory syndrome virus (PRRSv) in endemic settings: lessons learned in the U.S. Content: Since its emergence in the late 1980\u2019s, the porcine reproductive and respiratory syndrome virus (PRRSv) has posed a significant challenge to the pig industry worldwide. Since then, a number of epidemiological tools have been created to support control and eventual elimination of the disease at the farm and regional levels. Still, many aspects of the disease dynamics are yet-to-be elucidated, such as what are the economically optimal control strategies at the farm and regional level, what is the role that the voluntary regional control programs may play, how to optimize the use of molecular tools for surveillance and monitoring in infected settings, what is the full impact of the disease in a farm, or what is the relative contribution of alternative transmission routes on the occurrence of PRRSv outbreaks. Here, we summarize a number of projects demonstrating the use of novel analytical tools in the assessment of PRRSv epidemiology in the United States. Results presented demonstrate how quantitative analysis of routinely collected data may help in understanding regional epidemiology of PRRSv and to quantify its full impact, and how the integration of phylodynamic methods as a standard tool for molecular surveillance of PRRSv might help to inform control and prevention strategies in high-risk epidemiological situations. Ultimately, these tools will help to support PRRSv control at farm and regional levels in endemically infected settings.", "qid": 13, "docid": "mcywx9ol", "rank": 23, "score": 6.434599876403809}, {"content": "Title: Preliminary investigation on feline coronavirus presence in the reproductive tract of the tom cat as a potential route of viral transmission Content: OBJECTIVES: Feline infectious peritonitis (FIP) is an immune-mediated disease initiated by feline coronavirus (FCoV) infection. To date, the only proven route of transmission is the faecal\u2013oral route, but a possible localisation of FCoV in the reproductive tract of tom cats is of concern, owing to the involvement of the male reproductive tract during FIP and to the presence of reproduction disorders in FCoV-endemic feline catteries. The aim of the study was to investigate the presence and localisation of FCoV in semen and/or in the reproductive tract of tom cats, and its possible association with seroconversion and viraemic phase. METHODS: Blood, serum, semen and/or testicle samples were obtained from 46 tom cats. Serology was performed on 38 serum samples, nested reverse transcriptase PCR (nRT-PCR) and reverse transcriptase quantitative PCR (RT-qPCR) were performed on 39 blood samples and on 17 semen samples, and histology, immunohistochemistry and nRT-PCR were performed on 39 testicles. RESULTS: Twenty-four of 38 serum samples were positive on serology. Semen samples were negative on RT-PCR and RT-qPCR for FCoV, while all blood samples were negative at both molecular methods, except for one sample positive at RT-qPCR with a very low viral load. All testicles were negative at immunohistochemistry, while six were positive at nRT-PCR for FCoV. Serology and blood PCR results suggest that the virus was present in the environment, stimulating transient seroconversion. FCoV seems not to localise in the semen of tom cats, making the venereal route as a way of transmission unlikely. Although viral RNA was found in some testicles, it could not be correlated with the viraemic phase. CONCLUSIONS AND RELEVANCE: In the light of these preliminary results, artificial insemination appears safer than natural mating as it eliminates the direct contact between animals, thus diminishing the probability of faecal\u2013oral FCoV transmission.", "qid": 13, "docid": "b8y3nhcs", "rank": 24, "score": 6.434199810028076}, {"content": "Title: COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission Content: The recent coronavirus disease (COVID-19), caused by SARS-CoV-2, is inarguably the most challenging coronavirus outbreak relative to the previous outbreaks involving SARS-CoV and MERS-CoV. With the number of COVID-19 cases now exceeding 2 million worldwide, it is apparent that (i) transmission of SARS-CoV-2 is very high and (ii) there are large variations in disease severity, one component of which may be genetic variability in the response to the virus. Controlling current rates of infection and combating future waves require a better understanding of the routes of exposure to SARS-CoV-2 and the underlying genomic susceptibility to this disease. In this mini-review, we highlight possible genetic determinants of COVID-19 and the contribution of aerosol exposure as a potentially important transmission route of SARS-CoV-2.", "qid": 13, "docid": "kj6m72jt", "rank": 25, "score": 6.309599876403809}, {"content": "Title: Transmission of SARS-CoV-2 via fecal-oral and aerosols-borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Content: The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "qid": 13, "docid": "9of9gijc", "rank": 26, "score": 6.309000015258789}, {"content": "Title: Transmission of SARS-CoV-2 via fecal-oral and aerosols\u2013borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Content: Abstract The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "qid": 13, "docid": "ioo17gc3", "rank": 27, "score": 6.308999061584473}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19. Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., \u03b1?, \u03b2?, \u03b3, and \u03b4-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.", "qid": 13, "docid": "kkknzw2i", "rank": 28, "score": 6.298799991607666}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19 Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world To date, seven known strains of HCoVs belonging to four genera (i e , alpha?, beta?, gamma, and delta-CoV) have been recognized;the latest one has been identified as the SARS-CoV-2 Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19 Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19 There is a greater need to better understand the mechanisms and risk factors of transmission routes To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear Therefore, there is an urgent need for update data on SARS-CoV-2 Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020", "qid": 13, "docid": "o908k448", "rank": 29, "score": 6.29879903793335}, {"content": "Title: Recreational waters - A potential transmission route for SARS-CoV-2 to humans? Content: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "qid": 13, "docid": "nl8z6u5v", "rank": 30, "score": 6.291600227355957}, {"content": "Title: Recreational waters \u2013 A potential transmission route for SARS-CoV-2 to humans? Content: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "qid": 13, "docid": "rfkcjpl1", "rank": 31, "score": 6.291599273681641}, {"content": "Title: What makes a foodborne virus: comparison between coronaviruses with human noroviruses Content: In order to answer the question whether coronaviruses (CoVs) can be transmitted via foods, this review made a comparison between CoVs with the most recognized foodborne virus, human noroviruses (NoVs). As a result, although CoVs indeed have shown the possibilities to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission, they seem to be less persistent than NoVs towards common disinfection practices with alcohols, chlorine and ultraviolet (UV). More importantly, the chance of foodborne transmission of CoVs is considered low as CoVs mainly spread through the respiratory tract and there is no clear evidence showing CoVs can follow fecal-oral routes like human NoVs and other foodborne viruses.", "qid": 13, "docid": "zybdv7ic", "rank": 32, "score": 6.262199878692627}, {"content": "Title: Facemasks prevent influenza-like illness: implications for COVID-19 Content: The coronavirus disease 2019 (COVID-19) pandemic is causing a huge toll on individuals, families, communities and societies across the world. Currently, whether wearing facemasks in public should be a measure to prevent transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains contraversial.1 This is largely because there have been no randomized controlled trials (RCTs) for coronavirus to directly support this. However, lessons may be taken from published RCTs examining influenza-like illness (ILI).2,3 Recent studies suggested that SARS-CoV-2 shares similar transmission route with influenza virus,4 and the incidence of community transmission of SARS-CoV-2 in individuals with ILI is high.5 Therefore, we undertook this meta-analysis of RCTs examining the efficacy of wearing facemasks to prevent ILI in community settings, irrespective of confirmatory testing for the causative virus. We undertook a systematic literature search for RCTs related to facemasks and ILI between 1966 and April 2020 using PUBMED, EMBASE, and Cochrane library. RCTs undertaken in community (not hospital) settings comparing wearing and not wearing facemasks for ILI were included. Incidence of ILI (e.g., fever, cough, headache, sore throat, aches or pains in muscles or joints) was estimated per group. Relative risk (RR) and 95% confidence interval (CI) were calculated. We screened 899 related abstracts and eventually included 8 RCTs (Figure S1). Basic characteristics and quality of included RCTs are listed in Supplement. Participants wearing facemasks had a significantly lower risk of developing ILI than those not wearing facemasks (pooled RR=0.81, 95% CI: 0.70-0.95) and there was no heterogeneity (Figure 1). The decreased risk of ILI was more pronounced if everyone wore facemask irrespective of whether they were infected or not (RR=0.77, 95% CI: 0.65-0.91), compared to those wearing facemasks when infected (RR=0.95, 95% CI: 0.58-1.56) or uninfected (RR=1.26, 95% CI: 0.69-2.31). This study shows that wearing facemasks, irrespective of infection status, is effective in preventing ILI spread in the community. This situation mirrors what is happening now in public settings where we do not know who has been infected and who has not. Although there are no RCTs of facemasks for SARS-CoV-2, as with other simple measures such as social distancing and handwashing, these data support the recommendation to wear facemasks in public to further reduce transmission of SARS-CoV-2 and flatten the curve of this pandemic, especially when social distancing is impractical, such as shopping, or travelling with public transport for work that cannot be done from home.", "qid": 13, "docid": "py38vnwc", "rank": 33, "score": 6.249599933624268}, {"content": "Title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal\u2013oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.", "qid": 13, "docid": "2e4gz2bo", "rank": 34, "score": 6.216100215911865}, {"content": "Title: Deep phylogenetic analysis of Orthocoronavirinae genomes traces the origin, evolution and transmission route of 2019 novel coronavirus Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Today, it appears as a threat to human civilization. Scientists and medical practitioners across the world are involved to trace out the origin and evolution of SARS-CoV-2 (also called 2019 novel coronavirus and referred as 2019-nCoV), its transmission route, cause of pathogenicity, and possible remedial action. In this work, we aim to find out the origin, evolutionary patternthat led to its pathogenicity and possible transmission pathway of 2019-nCoV. To achieve the aims we conducted a large-scale deep phylogenetic analysis on the 162 complete Orthocoronavirinae genomes consisting of four genera namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus, their gene trees analysis and subsequently genome and gene recombination analyses. Our analyses revealed that i) bat, pangolin and anteater are the natural hosts of 2019-nCoV, ii) outbreak of 2019-nCoV took place via inter-intra species transmission mode, iii) host-specific adaptive mutation made 2019-nCoV more virulent, and the presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity. Highlights Orthocoronavirinae genome phylogeny revealed that bat, pangolin and anteater are natural reservoir hosts of novel coronavirus (2019-nCoV/SARS-CoV-2). Host-specific adaptive mutation occurred among the coronaviruses. Transmission of 2019-nCoV to human took place by inter-intra species mode of transmission. Presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity.", "qid": 13, "docid": "fs07zdu6", "rank": 35, "score": 6.197800159454346}, {"content": "Title: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Content: At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.", "qid": 13, "docid": "co1mu99a", "rank": 36, "score": 6.180300235748291}, {"content": "Title: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Content: Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.", "qid": 13, "docid": "epcel2ez", "rank": 37, "score": 6.180299282073975}, {"content": "Title: A scoping review on bio-aerosols in healthcare and the dental environment Content: BACKGROUND: Bio-aerosols originate from different sources and their potentially pathogenic nature may form a hazard to healthcare workers and patients. So far no extensive review on existing evidence regarding bio-aerosols is available. OBJECTIVES: This study aimed to review evidence on bio-aerosols in healthcare and the dental setting. The objectives were 1) What are the sources that generate bio-aerosols?; 2) What is the microbial load and composition of bio-aerosols and how were they measured?; and 3) What is the hazard posed by pathogenic micro-organisms transported via the aerosol route of transmission? METHODS: Systematic scoping review design. Searched in PubMed and EMBASE from inception to 09-03-2016. References were screened and selected based on abstract and full text according to eligibility criteria. Full text articles were assessed for inclusion and summarized. The results are presented in three separate objectives and summarized for an overview of evidence. RESULTS: The search yielded 5,823 studies, of which 62 were included. Dental hand pieces were found to generate aerosols in the dental settings. Another 30 sources from human activities, interventions and daily cleaning performances in the hospital also generate aerosols. Fifty-five bacterial species, 45 fungi genera and ten viruses were identified in a hospital setting and 16 bacterial and 23 fungal species in the dental environment. Patients with certain risk factors had a higher chance to acquire Legionella in hospitals. Such infections can lead to irreversible septic shock and death. Only a few studies found that bio-aerosol generating procedures resulted in transmission of infectious diseases or allergic reactions. CONCLUSION: Bio-aerosols are generated via multiple sources such as different interventions, instruments and human activity. Bio-aerosols compositions reported are heterogeneous in their microbiological composition dependent on the setting and methodology. Legionella species were found to be a bio-aerosol dependent hazard to elderly and patients with respiratory complaints. But all aerosols can be can be hazardous to both patients and healthcare workers.", "qid": 13, "docid": "oiat9mq9", "rank": 38, "score": 6.176300048828125}, {"content": "Title: Transmission of SARS-CoV-2: an update of current literature Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2\u2014respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.", "qid": 13, "docid": "cfv0ta10", "rank": 39, "score": 6.171299934387207}, {"content": "Title: A new transmission route for the propagation of the SARS-CoV-2 coronavirus Content: We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.", "qid": 13, "docid": "4ah705nc", "rank": 40, "score": 6.165800094604492}, {"content": "Title: Is sweat a possible route of transmission of SARS-CoV-2? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, in part due to the highly infectious nature of the disease. Because SARS-CoV-2 is new, much is unknown regarding mechanisms of transmission, and such information is urgently needed. Here, based on previous findings from related human betacoronaviruses, it is suggested that one possible route of transmission may be via infectious sweat. It is suggested that research be conducted in order to determine whether sweat in SARS-CoV-2 infected individuals harbors virus in quantities that can infect others. Findings could be used for formulations of mitigation strategies and empirically based public health messaging.", "qid": 13, "docid": "5cygqkgk", "rank": 41, "score": 6.132400035858154}, {"content": "Title: Probable transmission routes of the influenza virus in a nosocomial outbreak. Content: Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers' routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.", "qid": 13, "docid": "rpu6aewp", "rank": 42, "score": 6.07919979095459}, {"content": "Title: A Review on 2019 Novel Coronavirus Pneumonia in Ophthalmology. Content: Purpose: To investigate the possibility of ocular involvement in the 2019-novel coronavirus infectious (2019-nCoV) and vital preventive measures in the field of ophthalmology.Methods: All the studies that were most relevant to the 2019-nCoV ocular involvement and routes of transmission, especially in the field of ophthalmology, thoroughly reviewed.Results: From the ocular perspective, conjunctivitis may be the first presenting symptom of 2019-nCoV, so, we as ophthalmologists are at the forefront of exposure with newly infected patients. Although transconjunctival aerosol is a suspected but, the main route of transmission is the known respiratory droplets which will be more significant due to close contact in the field of ophthalmology. This review advise a set of recommendation for preventive care to minimize cross-infection of 2019-nCoV.Conclusions: Ophthalmologists have an essential role in guiding cross-infection control measures between patients and staff. Until a vaccine is created, public health strategies are likely the best weapons against this invisible enemy.", "qid": 13, "docid": "dddcles3", "rank": 43, "score": 6.057600021362305}, {"content": "Title: A Review on 2019 Novel Coronavirus Pneumonia in Ophthalmology Content: Purpose: To investigate the possibility of ocular involvement in the 2019-novel coronavirus infectious (2019-nCoV) and vital preventive measures in the field of ophthalmology.Methods: All the studies that were most relevant to the 2019-nCoV ocular involvement and routes of transmission, especially in the field of ophthalmology, thoroughly reviewed.Results: From the ocular perspective, conjunctivitis may be the first presenting symptom of 2019-nCoV, so, we as ophthalmologists are at the forefront of exposure with newly infected patients. Although transconjunctival aerosol is a suspected but, the main route of transmission is the known respiratory droplets which will be more significant due to close contact in the field of ophthalmology. This review advise a set of recommendation for preventive care to minimize cross-infection of 2019-nCoV.Conclusions: Ophthalmologists have an essential role in guiding cross-infection control measures between patients and staff. Until a vaccine is created, public health strategies are likely the best weapons against this invisible enemy.", "qid": 13, "docid": "sfu7k63b", "rank": 44, "score": 6.057599067687988}, {"content": "Title: Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens Content: BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text] ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. CONCLUSIONS: Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text] ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.", "qid": 13, "docid": "jy63p793", "rank": 45, "score": 6.002099990844727}, {"content": "Title: Comparison of the COVID-19 infection risks by close contact and aerosol transmission Content: A comprehensive understanding of the transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance for the effective control of the spread of Corona Virus Disease 2019 (COVID-19). Human-to-human transmission by close contact where large respiratory droplets play a significant role has been established as the main transmission route. At the same time the transmission by small aerosol is getting increasing attention. There is no distinct boundary between droplets and aerosol in nature so it is natural to investigate the infection risk due to aerosol. Here, we utilized a newly developed dose-response relation, combined with a box model for the exposure estimation, to quantitatively evaluate the infection risk of SARS-CoV-2 through aerosol transmission and compared with the risk due to close contact. The results indicated that the median infection risk via aerosol transmission was about 3.7x10-5 (95% confidence interval: 3.5x10-6 to 4.4x10-4) for one hour of exposure in a room with the size of 10 m (width)x10 m (length)x3 m (height) with one infected individual in it. The risk was more than three orders of magnitude lower than the risk at short distance, about 12.8% within 1 m, based on a meta-analysis. A simple exponential regression model Risk=10-0.90xD+0.10 (D<=5 m) could be utilized to characterize the magnitude of infection risk in the considered scenario based on the distance D from the infected individual. With prolonged exposure duration and large exposed population, the infection caused by aerosol transmission could be considerable, thus it is necessary to be cautious for the potential aerosol transmission risk in such situations.", "qid": 13, "docid": "kt76tu24", "rank": 46, "score": 5.968500137329102}, {"content": "Title: Vaccine Strategies Content: The new technologies of genomics, proteomics, and molecular immunology have led to an impressive increase in our knowledge of all aspects of virology, providing insights that can guide new vaccine concepts. When developing a new vaccine, the choice of approach is made very much on a case-by-case basis, and for a given virus is driven by knowledge its pathogenesis, serotype diversity, antigenic variation, immune evasion mechanisms, latency and route of transmission. High importance is given to what type of immunity arises as a result of natural infection and whether the pathogen can cause persistent and/or repeated infections in a single host. This article discusses the medical need for new human viral vaccines and focuses on the strategies available for their development and some of the challenges posed by the more difficult targets.", "qid": 13, "docid": "b4u4yzjh", "rank": 47, "score": 5.917200088500977}, {"content": "Title: Transmission routes of respiratory viruses among humans Content: Respiratory tract infections can be caused by a wide variety of viruses. Airborne transmission via droplets and aerosols enables some of these viruses to spread efficiently among humans, causing outbreaks that are difficult to control. Many outbreaks have been investigated retrospectively to study the possible routes of inter-human virus transmission. The results of these studies are often inconclusive and at the same time data from controlled experiments is sparse. Therefore, fundamental knowledge on transmission routes that could be used to improve intervention strategies is still missing. We here present an overview of the available data from experimental and observational studies on the transmission routes of respiratory viruses between humans, identify knowledge gaps, and discuss how the available knowledge is currently implemented in isolation guidelines in health care settings.", "qid": 13, "docid": "2ewz8ok4", "rank": 48, "score": 5.914899826049805}, {"content": "Title: Coronavirus disease 2019 (COVID-19): research progress and clinical practice Content: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by SARS-CoV-2 As of March 30, 2020, there have been 693,224 reported patients with COVID-19 worldwide, with 1,446 in Japan Currently, although aspects of the route of transmission are unclear, infection by contact and by inhaling droplets is considered to be the dominant transmission route Inflammatory symptoms in the upper respiratory tract persist for several days to 1 week after onset, and in some patients symptoms of pneumonia worsen and become severe The presence of underlying diseases and advanced age are risk factors for increased severity Diagnosis is based on detection of SARS-CoV-2 by polymerase chain reaction (PCR) testing of nasopharyngeal swabs or sputum Symptomatic management is the main treatment for this disease Although the efficacy of several agents is currently being tested, at present there is no effective therapeutic agent To prevent infection, in addition to standard preventive measures, measures that counteract infection by contact and droplet inhalation are important In addition, if procedures that cause aerosolization of virus are used, then measures that prevent airborne infection should be implemented", "qid": 13, "docid": "cz3qt5qd", "rank": 49, "score": 5.909999847412109}, {"content": "Title: Airborne or Fomite Transmission for Norovirus? A Case Study Revisited Content: Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue. Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades. This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred. Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission? This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns. Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model. These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach. The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route. This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.", "qid": 13, "docid": "6eb2jgl7", "rank": 50, "score": 5.905399799346924}, {"content": "Title: Exploration of the Effectiveness of Social Distancing on Respiratory Pathogen Transmission Implicates Environmental Contributions Content: Background. In both military and civilian settings, transmission of respiratory pathogens may be due to person-to-person and environmental contributions. This possibility was explored in a military training setting, where rates of febrile respiratory illness (FRI) often reach epidemic levels. Methods. Population size and FRI rates were monitored over 10 months in the units of 50\u201390 individuals. Some units were open to the influx of potentially infectious convalescents (hereafter referred to as \u201copen units,\u201d and some were closed to such an influx (hereafter referred to as \u201cclosed units\u201d). Virologic testing and polymerase chain reaction analysis were used to detect adenovirus on surface structures. Results. The odds ratio (OR) associated with FRI in closed units, compared with open units, was 1.13 (95% confidence interval [CI], 0.99\u20131.28). The OR in units with a population greater than the median size, compared with units with a population lower than the median size was 1.38 (95% CI, 1.23\u20131.55). Between 5% and 9% of surface samples obtained from selected units harbored viable adenovirus. Conclusions. FRI rates were not reduced in units that were closed to potentially contagious individuals. These findings imply that the primary source of the pathogen is likely environmental rather than human, and they underscore what is known about other virus types. Diligence in identifying the relative roles of different transmission routes is suggested for civilian settings similar to those described in the current study.", "qid": 13, "docid": "7aox3zx0", "rank": 51, "score": 5.894100189208984}, {"content": "Title: A Mathematical Framework for Predicting Lifestyles of Viral Pathogens Content: Despite being similar in structure, functioning, and size, viral pathogens enjoy very different, usually well-defined ways of life. They occupy their hosts for a few days (influenza), for a few weeks (measles), or even lifelong (HCV), which manifests in acute or chronic infections. The various transmission routes (airborne, via direct physical contact, etc.), degrees of infectiousness (referring to the viral load required for transmission), antigenic variation/immune escape and virulence define further aspects of pathogenic lifestyles. To survive, pathogens must infect new hosts; the success determines their fitness. Infection happens with a certain likelihood during contact of hosts, where contact can also be mediated by vectors. Besides structural aspects of the host-contact network, three parameters appear to be key: the contact rate and the infectiousness during contact, which encode the mode of transmission, and third the immunity of susceptible hosts. On these grounds, what can be said about the reproductive success of viral pathogens? This is the biological question addressed in this paper. The answer extends earlier results of the author and makes explicit connection to another basic work on the evolution of pathogens. A mathematical framework is presented that models intra- and inter-host dynamics in a minimalistic but unified fashion covering a broad spectrum of viral pathogens, including those that cause flu-like infections, childhood diseases, and sexually transmitted infections. These pathogens turn out as local maxima of numerically simulated fitness landscapes. The models involve differential and integral equations, agent-based simulation, networks, and probability.", "qid": 13, "docid": "z5bbyvju", "rank": 52, "score": 5.894099235534668}, {"content": "Title: [Strengthening basic and clinical research on ocular infection caused by coronavirus]. Content: This article was published ahead of print on the official website of Chinese Jounal of Ophthalmology on February 19, 2020. The prevention and treatment of coronavirus disease 2019 (COVID-2019) has reached the critical stage in China. Ocular surface represents a possible route for infection. Based on the previous studies and our own research, we summarize the potential transmission route and clinical symptoms of COVID-2019 in the eye, as well as the further prevention and research, with the expectation of contributing to the development in the field of infectious eye disease in China. (Chin J Ophthalmol, 2020, 56:250-252).", "qid": 13, "docid": "jtfyu4sa", "rank": 53, "score": 5.854599952697754}, {"content": "Title: Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health Content: Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 countries affected. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "qid": 13, "docid": "12sbikmx", "rank": 54, "score": 5.850800037384033}, {"content": "Title: Potential Fecal Transmission of SARS-CoV-2: Current Evidence and Implications for Public Health Content: Abstract Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 affected countries. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally-mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "qid": 13, "docid": "ruk46455", "rank": 55, "score": 5.850799083709717}, {"content": "Title: Observations about sexual and other routes of SARS\u2010CoV\u20102 (COVID\u201019) transmission and its prevention Content: Sexual contact has been proposed as a route of transmission for the SARS-CoV-2 virus, which raises the question of alternate routes of transmission.", "qid": 13, "docid": "uu8ft703", "rank": 56, "score": 5.820499897003174}, {"content": "Title: Overview of new vaccines and technologies Content: Abstract Molecular technology has given us a greater insight into the aetiology of disease, the functioning of the immune system and the mode of action of veterinary pathogens. The knowledge gained has been used to develop new vaccines with specific, reactive antigens which elicit protective immune mediated responses (humoral and/or cell mediated) in the host. These vaccines should not burden the immune system by initiating responses against non-essential antigens. However, the efficacy of these vaccines is only as good as the delivery technology or route used to present them to the immune system. Some vaccines, traditionally given by the parenteral route, are now given by the natural route; either orally or intranasally. Two major advantages, often interrelated, are the rapid onset of immunity and stimulation of the local, mucosal immunity. These new technologies are now making an impact on current vaccine development. The balance has to be found between what is technologically feasible and what will provide at least as good a protective immunity as current, conventional vaccines. As new and emerging diseases appear globally, new opportunities arise for molecular and conventional technologies to be applied to both the development and delivery of novel vaccines, as well as the improvement of vaccines in current use.", "qid": 13, "docid": "34nnp9cv", "rank": 57, "score": 5.807000160217285}, {"content": "Title: Risk of SARS-CoV-2 infection from contaminated water systems Content: Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.", "qid": 13, "docid": "ycdok8fc", "rank": 58, "score": 5.80210018157959}, {"content": "Title: Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care. Content: The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 \u00b5m) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.", "qid": 13, "docid": "izxqtril", "rank": 59, "score": 5.785200119018555}, {"content": "Title: Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care Content: The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 \u00b5m) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.", "qid": 13, "docid": "k4twbzkm", "rank": 60, "score": 5.785199165344238}, {"content": "Title: Identifying airborne transmission as the dominant route for the spread of COVID-19 Content: Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease. By analyzing the trend and mitigation measures in Wuhan, China, Italy, and New York City, from January 23 to May 9, 2020, we illustrate that the impacts of mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.", "qid": 13, "docid": "9ye2okm5", "rank": 61, "score": 5.771299839019775}, {"content": "Title: Toxoplasma gondii: from animals to humans. Content: Toxoplasmosis is one of the more common parasitic zoonoses world-wide. Its causative agent, Toxoplasma gondii, is a facultatively heteroxenous, polyxenous protozoon that has developed several potential routes of transmission within and between different host species. If first contracted during pregnancy, T. gondii may be transmitted vertically by tachyzoites that are passed to the foetus via the placenta. Horizontal transmission of T. gondii may involve three life-cycle stages, i.e. ingesting infectious oocysts from the environment or ingesting tissue cysts or tachyzoites which are contained in meat or primary offal (viscera) of many different animals. Transmission may also occur via tachyzoites contained in blood products, tissue transplants, or unpasteurised milk. However, it is not known which of these routes is more important epidemiologically. In the past, the consumption of raw or undercooked meat, in particular of pigs and sheep, has been regarded as a major route of transmission to humans. However, recent studies showed that the prevalence of T. gondii in meat-producing animals decreased considerably over the past 20 years in areas with intensive farm management. For example, in several countries of the European Union prevalences of T. gondii in fattening pigs are now <1%. Considering these data it is unlikely that pork is still a major source of infection for humans in these countries. However, it is likely that the major routes of transmission are different in human populations with differences in culture and eating habits. In the Americas, recent outbreaks of acute toxoplasmosis in humans have been associated with oocyst contamination of the environment. Therefore, future epidemiological studies on T. gondii infections should consider the role of oocysts as potential sources of infection for humans, and methods to monitor these are currently being developed. This review presents recent epidemiological data on T. gondii, hypotheses on the major routes of transmission to humans in different populations, and preventive measures that may reduce the risk of contracting a primary infection during pregnancy.", "qid": 13, "docid": "23feyq29", "rank": 62, "score": 5.766600131988525}, {"content": "Title: How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes Content: The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-province routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.", "qid": 13, "docid": "4k1i6y98", "rank": 63, "score": 5.752799987792969}, {"content": "Title: Evidence for gastrointestinal infection of SARS-CoV-2 Content: The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.", "qid": 13, "docid": "7odpslba", "rank": 64, "score": 5.750400066375732}, {"content": "Title: Chapter 3 Routes of Transmission in the Food Chain Content: Abstract More than 250 different foodborne diseases have been described to date, annually affecting about one-third of the world's population. The incidence of foodborne diseases has been underreported and underestimated, and the asymptomatic presentation of some of the illnesses, worldwide heterogeneities in reporting, and the alternative transmission routes of certain pathogens are among the factors that contribute to this. Globalization, centralization of the food supply, transportation of food products progressively farther from their places of origin, and the multitude of steps where contamination may occur have made it increasingly challenging to investigate foodborne and waterborne outbreaks. Certain foodborne pathogens may be transmitted directly from animals to humans, while others are transmitted through vectors, such as insects, or through food handlers, contaminated food products or food-processing surfaces, or transfer from sponges, cloths, or utensils. Additionally, the airborne route may contribute to the transmission of certain foodborne pathogens. Complicating epidemiological investigations, multiple transmission routes have been described for some foodborne pathogens. Two types of transmission barriers, primary and secondary, have been described for foodborne pathogens, each of them providing opportunities for preventing and controlling outbreaks. Primary barriers, the most effective sites of prophylactic intervention, prevent pathogen entry into the environment, while secondary barriers prevent the multiplication and dissemination of pathogens that have already entered the environment. Understanding pathogen dynamics, monitoring transmission, and implementing preventive measures are complicated by the phenomenon of superspreading, which refers to the concept that, at the level of populations, a minority of hosts is responsible for the majority of transmission events.", "qid": 13, "docid": "hu1bheiy", "rank": 65, "score": 5.747099876403809}, {"content": "Title: Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets Content: While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to na\u00efve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes.", "qid": 13, "docid": "x4hdxx1t", "rank": 66, "score": 5.740499973297119}, {"content": "Title: Transmission Kinetics and histopathology induced by European Turkey Coronavirus during experimental infection of specific pathogen free turkeys Content: Numerous viruses, mostly in mixed infections, have been associated worldwide with poult enteritis complex (PEC). In 2008 a coronavirus (Fr\u2010TCoV 080385d) was isolated in France from turkey poults exhibiting clinical signs compatible with this syndrome. In the present study, the median infectious dose (ID (50))(,) transmission kinetics and pathogenicity of Fr\u2010TCoV were investigated in 10\u2010day\u2010old SPF turkeys. Results revealed a titre of 10(4.88) ID (50)/ml with 1 ID (50)/ml being beyond the limit of genome detection using a well\u2010characterized qRT\u2010PCR for avian coronaviruses. Horizontal transmission of the virus via the airborne route was not observed however, via the oro\u2010faecal route this proved to be extremely rapid (one infectious individual infecting another every 2.5 hr) and infectious virus was excreted for at least 6 weeks in several birds. Histological examination of different zones of the intestinal tract of the Fr\u2010TCoV\u2010infected turkeys showed that the virus had a preference for the lower part of the intestinal tract with an abundance of viral antigen being present in epithelial cells of the ileum, caecum and bursa of Fabricius. Viral antigen was also detected in dendritic cells, monocytes and macrophages in these areas, which may indicate a potential for Fr\u2010TCoV to replicate in antigen\u2010presenting cells. Together these results highlight the importance of good sanitary practices in turkey farms to avoid introducing minute amounts of virus that could suffice to initiate an outbreak, and the need to consider that infected individuals may still be infectious long after a clinical episode, to avoid virus dissemination through the movements of apparently recovered birds.", "qid": 13, "docid": "6qx0v28w", "rank": 67, "score": 5.73829984664917}, {"content": "Title: The Ocular Surface and the Coronavirus Disease 2019: Does a Dual \u2018Ocular Route\u2019 Exist? Content: Coronavirus disease 2019 (COVID-19) is an important health problem that was defined as a pandemic by the World Health Organization on 11 March 2020. Although great concern has been expressed about COVID-19 infection acquired through ocular transmission, its underlying mechanism has not currently been clarified. In the current work, we analyzed and elucidated the two main elements that should be taken into account to understand the \u201cocular route\u201d, both from a clinical and molecular point of view. They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein. Although it seems, at the moment, that there is a low risk of coronavirus spreading through tears, it may survive for a long time or replicate in the conjunctiva, even in absence of conjunctivitis signs, indicating that eye protection (e.g., protective goggles alone or in association with face shield) is advisable to prevent contamination from external droplets and aerosol.", "qid": 13, "docid": "g2a4f2ko", "rank": 68, "score": 5.7042999267578125}, {"content": "Title: A letter about the airborne transmission of sars-cov-2 based on the current evidence Content: World Health Organization has suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through person-to-person transmission and contact with contaminated surfaces. However, rapid spread of the coronavirus disease 2019 (COVID-19) suggests other routes such as airborne transmission may be involved. A few research studies have been conducted to evaluate the potential transmission of this virus through air. Although some studies have found no evidence of airborne transmission, other more recent work is proving the presence of SARS-CoV-2 even in public places. Also, the past experiences and knowledge about the mechanisms of similar viruses such as SARS-CoV support this hypothesis. It seems that the best decision at the moment is to follow a conservative approach, and accept the hypothesis that SARS-CoV-2 is able to be transmitted through air. By this, control measures could be employed to prevent further COVID-19 infection.", "qid": 13, "docid": "a1ha0hx4", "rank": 69, "score": 5.702300071716309}, {"content": "Title: Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective Content: An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "qid": 13, "docid": "dz8blrzm", "rank": 70, "score": 5.691500186920166}, {"content": "Title: Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective Content: An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) in Wuhan, China, now known as coronavirus disease 2019 (COVID\u201019), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID\u201019 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal\u2010oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID\u201019; (b) microbiological and virological investigations; (c) the role of fecal\u2010oral transmission; and (d) prevention and control of SARS\u2010CoV\u20102 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "qid": 13, "docid": "xj9md751", "rank": 71, "score": 5.69149923324585}, {"content": "Title: C19-TraNet: an empirical, global index-case transmission network of SARS-CoV-2 Content: Originating in Wuhan, the novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2), has astonished health-care systems across globe due to its rapid and simultaneous spread to the neighboring and distantly located countries. To gain the systems level understanding of the role of global transmission routes in the COVID-19 spread, in this study, we have developed the first, empirical, global, index-case transmission network of SARS-CoV-2 termed as C19-TraNet. We manually curated the travel history of country wise index-cases using government press releases, their official social media handles and online news reports to construct this C19-TraNet that is a spatio-temporal, sparse, growing network comprising of 187 nodes and 199 edges and follows a power-law degree distribution. To model the growing C19-TraNet, a novel stochastic scale free (SSF) algorithm is proposed that accounts for stochastic addition of both nodes as well as edges at each time step. A peculiar connectivity pattern in C19-TraNet is observed, characterized by a fourth degree polynomial growth curve, that significantly diverges from the average random connectivity pattern obtained from an ensemble of its 1,000 SSF realizations. Partitioning the C19-TraNet, using edge betweenness, it is found that most of the large communities are comprised of a heterogeneous mixture of countries belonging to different world regions suggesting that there are no spatial constraints on the spread of disease. This work characterizes the superspreaders that have very quickly transported the virus, through multiple transmission routes, to long range geographical locations alongwith their local neighborhoods.", "qid": 13, "docid": "g6zwxu35", "rank": 72, "score": 5.689599990844727}, {"content": "Title: Ventilation in the Dental Clinic: An Effective Measure to Control Droplets and Aerosols during the Coronavirus Pandemic and Beyond. Content: Clinical and epidemiological studies suggest that human-to-human transmission of coronavirus disease 2019 (COVID-19) most frequently occurs through virus-laden respiratory droplets discharged from infected individuals while coughing and sneezing. Aerosols can act as another potential transmission route. The World Health Organisation (WHO) has advised medical personnel to consider taking 'airborne precautions'. It is important to protect dentists and patients and reduce the amount of spatter produced during dental procedures. In order to prevent airborne transmission, dental offices should be sufficiently ventilated, with great emphasis placed upon removing bioaerosols.", "qid": 13, "docid": "db97z3nl", "rank": 73, "score": 5.686800003051758}, {"content": "Title: COVID-19: Transmission, prevention, and potential therapeutic opportunities Content: The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Despite intense research efforts worldwide, an effective vaccine and viable treatment options have eluded investigators. Therefore, infection prevention, early viral detection and identification of successful treatment protocols provide the best approach in controlling disease spread. In this review, current therapeutic options, preventive methods and transmission routes of COVID-19 are discussed.", "qid": 13, "docid": "6jsbh5or", "rank": 74, "score": 5.639999866485596}, {"content": "Title: On-site measurement of tracer gas transmission between horizontal adjacent flats in residential building and cross-infection risk assessment Content: Abstract Airborne transmission is a main spread mode of respiratory infectious diseases, whose frequent epidemic has brought serious social burden. Identifying possible routes of the airborne transmission and predicting the potential infection risk are meaningful for infectious disease control. In the present study, an internal spread route between horizontal adjacent flats induced by air infiltration was investigated. On-site measurements were conducted, and tracer gas technique was employed. Two measurement scenarios, closed window mode and open window mode, were compared. Using the calculated air change rate and mass fraction, the cross-infection risk was estimated using the Wells\u2013Riley model. It found that tracer gas concentrations in receptor rooms are one order lower than the source room, and the infection risks are also one order lower. Opening windows results in larger air change rate on the one hand, but higher mass fraction on the other hand. Higher mass fraction not necessarily results in higher infection risk as the pathogen concentration in the source room is reduced by the higher air change rate. In the present study, opening windows could significantly reduce the infection risk of the index room but slightly reduce the risks in receptor rooms. The mass fraction of air originated from the index room to the receptor units could be 0.28 and the relative cross-infection risk through the internal transmission route could be 9%, which are higher than the external spread through single-sided window flush. The study implicates that the horizontal transmission route induced by air infiltration should not be underestimated.", "qid": 13, "docid": "lyngx8kq", "rank": 75, "score": 5.630799770355225}, {"content": "Title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits Content: Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.", "qid": 13, "docid": "eumuid3r", "rank": 76, "score": 5.60830020904541}, {"content": "Title: Tropism of human adenovirus type 5-based vectors in swine and their ability to protect against transmissible gastroenteritis coronavirus. Content: The infection of epithelia] swine testicle and intestinal porcine epithelial (IPEC-1) cell lines by adenovirus type 5 (Ad5) has been studied in vitro by using an Ad5-luciferase recombinant containing the firefly luciferase gene as a reporter. Porcine cell lines supported Ad5 replication, showing virus titers, kinetics of virus production, and luciferase expression levels similar to those obtained in human 293 cells, which constitutively express the 5'-end 11% of the Ad5 genome. The tropism of Ad5-based vectors in swine and its ability to induce an efficient immune response against heterologous antigens expressed by foreign genes inserted in these vectors has been determined. Ad5 vectors replicate and express heterologous antigens in porcine lungs and mediastinal and mesenteric lymph nodes. Significant levels of heterologous antigen expression were also demonstrated in the small intestine (jejunum and ileum), but Ad5 replication in this organ was very poor, suggesting that Ad vectors undergo an abortive replication in the porcine small intestine. The tissues infected by Ad5 were dependent on the inoculation route. The oronasal route appeared to be best for inoculation of bronchus-associated lymphoid tissue infection, while the intraperitoneal route was best for gut-associated lymphoid tissue infection. Epithelial cells of bronchioles, macrophages, type II pneumocytes, and follicular dendritic cells were identified as targets for Ad5, while epithelial cells of the intestine were not infected by Ad5. Viruses with a deletion from 79.5 to 84.8 map units in the E3 region, with or without heterologous inserted genes, replicated to lower levels in porcine tissues than did wild-type Ad5. It was also shown that an Ad5 recombinant expressing the four antigenic sites (A, B, C, and D) of transmissible gastroenteritis coronavirus (TGEV) spike protein induced in swine immune responses which neutralized TGEV infectivity. In addition, porcine serum from Ad-TGEV-immune animals provide passive protection when mixed with fully virulent TGEV and orally administered to highly susceptible newborn piglets. These results taken together indicate that swine may be a good animal model for human Ad5 lung infection to aid in the evaluation of candidate adenovirus vaccines and that Ad5 may be suitable as a recombinant viral vaccine or for other applications in swine.", "qid": 13, "docid": "5q0lqjq3", "rank": 77, "score": 5.598800182342529}, {"content": "Title: Isolation of a porcine respiratory, non-enteric coronavirus related to transmissible gastroenteritis. Content: A porcine respiratory, non-enteric virus which is related to the coronavirus transmissible gastroenteritis virus (TGEV) has been isolated in pigs and in cell culture. The isolate was designated TLM 83. It has become very widespread and enzootic among the swine population in Belgium and in other swine raising countries. It causes an infection of the lungs and appears to spread by aerogenic route. It does not replicate in the enteric tract. The experimental infection in conventional and gnotobiotic pigs in isolation remains subclinical. The infection, either experimental or in the field, results in the formation of antibodies which neutralise the classical enteric TGEV. Based on this relationship, this virus is assumed to be a new TGEV-related porcine respiratory coronavirus or TGEV itself which has totally lost its tropism for the enteric tract.", "qid": 13, "docid": "j4a6ng8o", "rank": 78, "score": 5.5802001953125}, {"content": "Title: [Replication and transmission mechanisms of highly pathogenic human coronaviruses] Content: The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response Human highly pathogenic coronaviruses are hosted by humans and vertebrates Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses", "qid": 13, "docid": "iwy2nn17", "rank": 79, "score": 5.575099945068359}, {"content": "Title: [Replication and transmission mechanisms of highly pathogenic human coronaviruses]. Content: The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins. Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response. Human highly pathogenic coronaviruses are hosted by humans and vertebrates. Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes. This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses.", "qid": 13, "docid": "ms4xzxyv", "rank": 80, "score": 5.575098991394043}, {"content": "Title: Epidemiology of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 Content: In December, 2019, an infection outbreak occurred in Wuhan of unknown cause, which attracts intense attention. Shortly after the virus was identified with the name of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out and an information storm occurred. At that time, two important aspects: the stage and the links of epidemic, were unclear. Answers to the questions, what are the sources, how do infections occur, and who will be affected should be clarified as the outbreak continues to evolve. Furthermore, the epidemic process and the stage of epidemic should be explored and discussed. Based on information of SARS, middle east respiratory syndrome(MERS) and COVID-19, the links of epidemic (the sources, the routes of infection, and the susceptible population) will be discussed as well as the role of the natural and the social factors. Epidemiology characteristics of patients will be traced based on current information.", "qid": 13, "docid": "89qmvo9a", "rank": 81, "score": 5.574699878692627}, {"content": "Title: Epidemiology of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2. Content: In December, 2019, an infection outbreak occurred in Wuhan of unknown cause, which attracts intense attention. Shortly after the virus was identified with the name of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out and an information storm occurred. At that time, two important aspects: the stage and the links of epidemic, were unclear. Answers to the questions, what are the sources, how do infections occur, and who will be affected should be clarified as the outbreak continues to evolve. Furthermore, the epidemic process and the stage of epidemic should be explored and discussed. Based on information of SARS, middle east respiratory syndrome(MERS) and COVID-19, the links of epidemic (the sources, the routes of infection, and the susceptible population) will be discussed as well as the role of the natural and the social factors. Epidemiology characteristics of patients will be traced based on current information.", "qid": 13, "docid": "mxvbbkc4", "rank": 82, "score": 5.5746989250183105}, {"content": "Title: Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in Rhesus macaques Content: The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1\u00d7106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.", "qid": 13, "docid": "ih1py5n9", "rank": 83, "score": 5.571100234985352}, {"content": "Title: The 2019 novel coronavirus disease (COVID-19) pandemic: A zoonotic prospective Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus (CoV), has recently emerged as a significant pathogen for humans and the cause for the recent outbreak of the 2019 novel coronavirus disease (COVID-19) throughout the globe For developing any preventive measure, an understanding of the zoonotic pattern for this virus is a necessity We should have a clear knowledge of its reservoir host, its distribution pattern and spreading routes Information about zoonotic reservoirs and its transmission among them can help to understand the COVID-19 outbreaks In this article, we discuss about the bats as the zoonotic reservoir of several CoV strains, co-existence of bats and CoV/viruses, the sequence similarity of SARS-CoV-2 with bat SARS-like CoV, the probable source of the origin of SARS-CoV-2 strain and COVID-19 outbreak, intermediate host of CoVs and SARS-CoV-2, human to human transmission and the possibility to maintain the zoonotic barriers Our knowledge about the zoonotic reservoir of SARS-CoV-2 and its transmission ability may help develop the preventive measures and control for the future outbreak of CoV", "qid": 13, "docid": "l41pnvfd", "rank": 84, "score": 5.556000232696533}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 13, "docid": "6tod4abn", "rank": 85, "score": 5.552000045776367}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy() Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 13, "docid": "iaiosjlu", "rank": 86, "score": 5.551999092102051}, {"content": "Title: Prevention and control of COVID-19 in nursing homes, orphanages, and prisons Content: As the number of Coronavirus Disease (2019) (COVID-19) cases increase globally, countries are taking more aggressive preventive measures against this pandemic. Transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) include droplet and contact transmissions. There are also evidence of transmission through aerosol generating procedures (AGP) in specific circumstances and settings. Institutionalized populations without mobility and living in close proximity with unavoidable contact are especially vulnerable to higher risks of COVID-19 infection, such as the elderly in nursing homes, children in orphanages, and inmates in prisons. In these places, higher prevention and control measures are needed. In this study, we proposed prevention and control strategies for these facilities and provided practical guidance for general measures, health management, personal protection measures, and prevention measures in nursing homes, orphanages, and prisons, respectively.", "qid": 13, "docid": "picxa3je", "rank": 87, "score": 5.551998138427734}, {"content": "Title: Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Content: A countrywide survey in Oman revealed Middle Eastrespiratory syndrome coronavirus (MERS-CoV) nucleicacid in five of 76 dromedary camels. Camel-derivedMERS-CoV sequences (3,754 nucleotides assembled from partial sequences of the open reading frame (ORF)1a, spike, and ORF4b genes) from Oman and Qatar were slightly different from each other, but closely related to human MERS-CoV sequences from the same geographical areas, suggesting local zoonotic transmission. High viral loads in nasal and conjunctival swabs suggest possible transmission by the respiratory route.", "qid": 13, "docid": "c6y2knvy", "rank": 88, "score": 5.548900127410889}, {"content": "Title: Uncertainties about the transmission routes of 2019 novel coronavirus Content:", "qid": 13, "docid": "9hq8xdhi", "rank": 89, "score": 5.5269999504089355}, {"content": "Title: Family cluster of three recovered cases of pneumonia due to severe acute respiratory syndrome coronavirus 2 infection Content: The coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in late 2019 and has affected more than 1 270 000 people worldwide. The numbers of reported cases continue to rise and threaten global health. Transmissions among family members are frequently observed, although the route of transmission is partially known. Here we report three cases of SARS-CoV-2 infection within one family. Sequencing of the S gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. Following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. Our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/moderate pneumonia in COVID-19 cases.", "qid": 13, "docid": "zb71eul0", "rank": 90, "score": 5.526800155639648}, {"content": "Title: Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus Content: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.", "qid": 13, "docid": "dck3ecdd", "rank": 91, "score": 5.526599884033203}, {"content": "Title: Implication of COVID\u201019 in oral oncology practices in Brazil, Canada and the United States Content: The newly emerged Coronavirus disease 2019 (COVID\u201019) is an infectious disease that has spread rapidly throughout the world. The most common signs and symptoms are fever, dry cough and shortness of breath which can progress to severe viral pneumonia and multi\u2010organ failure in susceptive patients (Chen et al. 2020, Wang et al. 2020). Droplet transmission and person\u2010person transmission appear to be the main route of transmission of COVID\u201019, however asymptomatic patients are also carriers of the virus (Rothe et al. 2020).", "qid": 13, "docid": "dn7iuzq1", "rank": 92, "score": 5.52370023727417}, {"content": "Title: Ophthalmologic evidence against the interpersonal transmission of 2019 novel coronavirus through conjunctiva Content: Background: The emerging 2019 novel coronavirus (2019-nCoV) has pushed several countries into state of emergency all over the world. The possible transmission of 2019-nCoV by conjunctiva is controversial and has substantial public health implications. Methods: A retrospective cohort study was initiated to investigate the possible transmission of 2019-nCoV through aerosol contact with conjunctiva. We enrolled 67 cases of confirmed or suspected cases of novel coronavirus pneumonia (NCP) during 17-28 Jan 2020. Nasopharyngeal and conjunctival swabs were collected for real time RT-PCR analysis to detect 2019-nCoV. Results: 63 patients were identified as laboratory-confirmed NCP and the remaining four were suspected NCP. Conjunctival swab samples from one NCP patient yielded positive PCR results and two NCP patients yielded probable positive PCR results. None of the three patients had ocular symptoms. The only one NCP patient with conjunctivitis as the first symptom had negative conjunctival sac 2019-nCoV test. Conjunctival swab samples from the four suspected cases of NCIP were negative. Conclusion: 2019-nCoV can be detected in the conjunctival sac of patients with NCP. Through clinical analysis, viral transmission via the conjunctival route was not supported by the data. Good clinical protection can effectively cut off the transmission path.", "qid": 13, "docid": "w5t1ni4l", "rank": 93, "score": 5.5229997634887695}, {"content": "Title: [Preliminary result on the nosocomial infection of severe acute respiratory syndrome in one hospital of Beijing]. Content: OBJECTIVE To study the transmission route of severe acute respiratory syndrome (SARS) nosocomial infection. METHODS Ten identified SARS patients were selected from a general hospital in March. Survey was carried out through a standardized questionnaire provided by Chinese Center for Disease Control and Prevention. Contents of the questionnaire would include: history of contact with SARS patient, route of infection, methods used for protection and so on. RESULTS (1) Distribution os SARS patients were confined to 3 wards: 4, 5, and 6 on the 7, 8, 12, 13 and 14 floors in the west unit of the inpatient building. Most of the inpatients were elderly and having severe original diseases. (2) Index patients were the first generation source of transmission and they infected inpatients and medical staff, making them the second generation. People with latent infection who had close contact with SARS patients might also serve as the possible source of transmission. (3) The major transmission routes were: near distant droplet infection and close contact infection. There was also a clue to the probability of aerosol or droplet nuclei infection through air-conditioning and ventilation system. CONCLUSION Nosocomial infection appeared to be the main characteristic of the SARS epidemic in the early stage of this hospital. Other than close contact and near space airborne transmission of SARS virus, the possibility of long-distance aerosol transmission called for further epidemiological and experimental studies in the future.", "qid": 13, "docid": "q3e2d2mi", "rank": 94, "score": 5.520100116729736}, {"content": "Title: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Content: Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 \u00d7 10(4) to 1.7 \u00d7 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.", "qid": 13, "docid": "zmaw9lbz", "rank": 95, "score": 5.518599987030029}, {"content": "Title: Coronavirus (COVID-19) outbreak: what the department of endoscopy should know Content: Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection.", "qid": 13, "docid": "ayunmlpk", "rank": 96, "score": 5.5177001953125}, {"content": "Title: Early events during human coronavirus OC43 entry to the cell Content: The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.", "qid": 13, "docid": "ce4qclha", "rank": 97, "score": 5.517699241638184}, {"content": "Title: Role of viral bioaerosols in nosocomial infections and measures for prevention and control Content: Abstract The presence of patients with diverse pathologies in hospitals results in an environment that can be rich in various microorganisms including respiratory and enteric viruses, leading to outbreaks in hospitals or spillover infections to the community. All hospital patients are at risk of nosocomial viral infections, but vulnerable groups such as older adults, children and immuno-compromised/-suppressed patients are at particular risk of severe outcomes including prolonged hospitalization or death. These pathogens could transmit through direct or indirect physical contact, droplets or aerosols, with increasing evidence suggesting the importance of aerosol transmission in nosocomial infections of respiratory and enteric viruses. Factors affecting the propensity to transmit and the severity of disease transmitted via the aerosol route include the biological characteristics affecting infectivity of the viruses and susceptibility of the host, the physical properties of aerosol particles, and the environmental stresses that alter these properties such as temperature and humidity. Non-specific systematic and individual-based interventions designed to mitigate the aerosol route are available although empirical evidence of their effectiveness in controlling transmission of respiratory and enteric viruses in healthcare settings are sparse. The relative importance of aerosol transmission in healthcare setting is still an on-going debate, with particular challenge being the recovery of infectious viral bioaerosols from real-life settings and the difficulty in delineating transmission events that may also be a result of other modes of transmission. For the prevention and control of nosocomial infections via the aerosol route, more research is needed on identifying settings, medical procedures or equipment that may be associated with an increased risk of aerosol transmission, including defining which procedures are aerosol-generating; and on the effectiveness of systematic interventions on aerosol transmission of respiratory and enteric viruses in healthcare settings.", "qid": 13, "docid": "scmta88m", "rank": 98, "score": 5.517099857330322}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 13, "docid": "fqs40ivc", "rank": 99, "score": 5.5167999267578125}, {"content": "Title: The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients Content: In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate SARS-CoV-2 shedding in the excreta of COVID-19 patients. Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings of enrolled patients were extracted and analyzed. Pharyngeal swab, stool, and urine specimens were collected and tested for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Viral shedding at multiple time points in specimens was recorded, and its correlation analyzed with clinical manifestations and the severity of illness. A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. A total of 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, and this was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in the feces after the pharyngeal swabs turned negative. The duration of viral shedding from the feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did not differ between patients who tested positive and negative for SARS-CoV-2 RNA in the feces. Viral RNA was not detectable in urine specimens from 10 patients. Our results demonstrated the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route.", "qid": 13, "docid": "2brbgvqo", "rank": 100, "score": 5.507699966430664}]}
{"query": "what evidence is there related to COVID-19 super spreaders", "hits": [{"content": "Title: Super-Spreader Businesses and Risk of COVID-19 Transmission Content: Purpose: The United States has the highest number of confirmed COVID-19 cases in the world to date, with over 94,000 COVID-19-related deaths. The true risk of a COVID-19 resurgence as states prepare to reopen businesses is unknown. This paper aims to classify businesses by their risk of transmission and quantify the relationship between the density of super-spreader businesses and COVID-19 cases. Methods: We constructed a COVID-19 Business Transmission Risk Index based upon the frequency and duration of visits and square footage of businesses pre-pandemic in 2019 in 8 states (Massachusetts, Rhode Island, Connecticut, New Hampshire, Vermont, Maine, New York, and California). We used this index to classify businesses as super-spreaders. Then, we analyzed the association between the density of super-spreader businesses in a county and the rate of COVID-19 cases. We performed significance testing using a negative binomial regression. The main outcome of interest is the cumulative number of COVID-19 cases each week. Results: We found a positive association between the density of super-spreader businesses and COVID-19 cases. A 1 percentage point increase in the density of super-spreader businesses is associated with 5% higher COVID-19 cases, all else equal. Conclusion: Higher densities of super-spreader businesses are associated with higher rates of COVID-19 cases. This may have important implications for how states reopen super-spreader businesses.", "qid": 14, "docid": "8ngri1x0", "rank": 1, "score": 14.970999717712402}, {"content": "Title: Significance of super spreader events in COVID-19. Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 14, "docid": "na3vrf5q", "rank": 2, "score": 14.37399959564209}, {"content": "Title: Significance of super spreader events in COVID-19 Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 14, "docid": "p48bw6s4", "rank": 3, "score": 14.373998641967773}, {"content": "Title: COVID-19 Super-spreaders: Definitional Quandaries and Implications Content: Uncertainty around the role \u2018super-spreaders\u2019 play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "qid": 14, "docid": "s9dy7iyf", "rank": 4, "score": 13.280799865722656}, {"content": "Title: COVID-19 Super-spreaders: Definitional Quandaries and Implications Content: Uncertainty around the role 'super-spreaders' play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "qid": 14, "docid": "v0vjkwy9", "rank": 5, "score": 13.28079891204834}, {"content": "Title: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo COVID-19 data. Content: BACKGROUND Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using the COVID-19 data from the city Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-squared tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-squared test. OBJECTIVE We reanalyze the data from the city Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS We exclude the cases associated with the super-spreader and adopt more appropriate statistical methods, including the permutation test and Fisher's exact test, to reanalyze the COVID-19 data from the city Ningbo. RESULTS After excluding the cases related to the super-spreader, Fisher's exact test yields p-value=.84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of transmission rates of coronavirus between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval [0.5, 2.8]. CONCLUSIONS Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients.", "qid": 14, "docid": "1pnc889f", "rank": 6, "score": 12.656299591064453}, {"content": "Title: Comparison of Transmissibility of Coronavirus Between Symptomatic and Asymptomatic Patients: Reanalysis of the Ningbo COVID-19 Data Content: BACKGROUND: Since the outbreak of the novel coronavirus disease (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of the coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using COVID-19 data from the city of Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-square tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-square test. OBJECTIVE: We reanalyze the data from the city of Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS: We excluded the cases associated with the super-spreader and adopted a more appropriate statistical method, including the permutation test and the Fisher exact test, to reanalyze the COVID-19 data from the city of Ningbo. RESULTS: After excluding the cases related to the super-spreader, the Fisher exact test yields a P value of .84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of the coronavirus transmission rates between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval 0.5-2.8. CONCLUSIONS: Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we concluded that there is no difference in the transmission rates of coronavirus between symptomatic and asymptomatic patients.", "qid": 14, "docid": "o3b5zm5l", "rank": 7, "score": 12.656298637390137}, {"content": "Title: Super-spreaders in infectious diseases Content: Summary Early studies that explored host\u2013pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.", "qid": 14, "docid": "j74wnaef", "rank": 8, "score": 12.639100074768066}, {"content": "Title: A super-spreader of COVID-19 in Ningbo city in China Content: An outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly. It is imperative to control the epidemic by understanding the epidemiological feature, preventative quarantine, and effective hygiene measures. In the present study, we report a case of super-spreader who transmitted the disease to over twenty-eight persons in Ningbo, Zhejiang. Identifying and isolated super-spreaders, understanding the reasons behind the efficient transmission ability are important for the control and management of the ongoing COVID-19 pandemic.", "qid": 14, "docid": "37katpp3", "rank": 9, "score": 12.611800193786621}, {"content": "Title: Spatial super-spreaders and super-susceptibles in human movement networks Content: As lockdowns and stay-at-home orders start to be lifted across the globe, governments are struggling to establish effective and practical guidelines to reopen their economies. In dense urban environments with people returning to work and public transportation resuming full capacity, enforcing strict social distancing measures will be extremely challenging, if not practically impossible. Governments are thus paying close attention to particular locations that may become the next cluster of disease spreading. Indeed, certain places, like some people, can be\"super-spreaders.\"Is a bustling train station in a central business district more or less susceptible and vulnerable as compared to teeming bus interchanges in the suburbs? Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. Our proposed data-analytic framework is based on the daily-aggregated ridership data of public transport in Singapore. By constructing the directed and weighted human movement networks and integrating human flow intensity with two neighborhood diversity metrics, we are able to pinpoint super-spreader and super-susceptible locations. Our results reveal that most super-spreaders are also super-susceptibles and that counterintuitively, busy peripheral bus interchanges are riskier places than crowded central train stations. Our analysis is based on data from Singapore, but can be readily adapted and extended for any other major urban center. It therefore serves as a useful framework for devising targeted and cost-effective preventive measures for urban planning and epidemiological preparedness.", "qid": 14, "docid": "cywjp5jh", "rank": 10, "score": 11.53849983215332}, {"content": "Title: Reconstruction of Transmission Pairs for novel Coronavirus Disease 2019 (COVID-19) in mainland China: Estimation of Super-spreading Events, Serial Interval, and Hazard of Infection Content: BACKGROUND: Knowledge on the epidemiological features and transmission patterns of COVID-19 is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1,407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9,120 COVID-19 confirmed cases reported during January 15 - February 29, 2020. Statistical model fittings were used to identify the super-spreaders and estimate serial interval distributions. Age and gender-stratified hazard of infection were estimated for household versus non-household transmissions. RESULTS: There were 34 primary cases identified as super-spreaders, with 5 super-spreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% CrI: 4.4, 5.5) and 5.2 (95% CrI: 4.9, 5.7) days for household transmissions and 5.2 (95% CrI: 4.6, 5.8) and 5.3 (95% CrI: 4.9, 5.7) days for non-household transmissions, respectively. Hazard of being infected outside of households is higher for age between 18 and 64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Non-negligible frequency of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced non-pharmaceutical interventions to mitigate this pandemic.", "qid": 14, "docid": "55f2cno3", "rank": 11, "score": 11.469099998474121}, {"content": "Title: Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever Content: BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (\u2018super-spreaders\u2019), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.", "qid": 14, "docid": "q9lfnu6s", "rank": 12, "score": 11.411199569702148}, {"content": "Title: Connecting the Dots of COVID-19 Transmissions in India Content: Witnessing its first case in late January 2020 India has seen a sharp rise in the number of positive cases of COVID-19. 34 States/UT (s) of the country have been found to be affected by the pandemic to date. We in this work, study the progress of COVID-19 pandemic in India. We aim to create transmission network visualization (s) of COVID-19 in India and perform analysis upon them. Using the transmission networks obtained we attempt to find the possible Super Spreader Individual (s) and Super Spreader Events (SSE) responsible for the outbreak in their respective regions. We discuss the potentials of network analysis in mitigating the further spread of the disease. This is one of the initial studies of the outbreak in India and the first attempt to study the pandemic in the country from a transmission network perspective.", "qid": 14, "docid": "d91t5o01", "rank": 13, "score": 11.324899673461914}, {"content": "Title: Unlinking super-linkers: the topology of epidemic response (Covid-19) Content: A key characteristic of the spread of infectious diseases is their ability to use efficient transmission paths within contact graphs. This enables the pathogen to maximise infection rates and spread within a target population. In this work, we devise techniques to localise infections and decrease infection rates based on a principled analysis of disease transmission paths within human-contact networks (proximity graphs). Experimental results of disease spreading shows that that at low visibility rates contact tracing slows disease spreading. However to stop disease spreading, contact tracing requires both significant visibility (at least 60%) into the proximity graph and the ability to place half of the population under isolation. We find that pro-actively isolating super-links -- key proximity encounters -- has significant benefits: targeted isolation of a fourth of the population based on 35% visibility into the proximity graph prevents an epidemic outbreak. It turns out that isolating super-spreaders is more effective than contact tracing and testing but less effective than targeting super-links. We highlight the important role of topology in epidemic outbreaks. We argue that proactive innoculation of a population by disabling super-links and super-spreaders may have an important complimentary role alongside contact tracing and testing as part of a sophisticated public-health response to epidemic outbreaks.", "qid": 14, "docid": "qla3go2i", "rank": 14, "score": 11.292499542236328}, {"content": "Title: Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea Content: Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of \u2265 38.5\u00b0C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38\u201322.30; P = 0.016), pulmonary infiltration of \u2265 3 lung zones (aOR, 7.33; 95% CI, 1.93\u201327.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09\u20131.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.", "qid": 14, "docid": "v5egtgdo", "rank": 15, "score": 11.288700103759766}, {"content": "Title: Modeling COVID-19 on a network: super-spreaders, testing and containment Content: We use a model of covid-19 spread, an SEIR agent-based model on a graph, which takes into account several important real-life attributes of covid-19: Super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We provide simulation results and mathematical arguments to argue that certain results of our simulations hold in more general settings. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to get suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, this model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution.", "qid": 14, "docid": "7kovd82v", "rank": 16, "score": 10.964599609375}, {"content": "Title: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease Content: Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014\u201315 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading.", "qid": 14, "docid": "414grqif", "rank": 17, "score": 10.894800186157227}, {"content": "Title: Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase Content: Background Coronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC). Method Using the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020. Results Using spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters. Conclusion Compared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.", "qid": 14, "docid": "901m6zw0", "rank": 18, "score": 10.795299530029297}, {"content": "Title: Importance of Interaction Structure and Stochasticity for Epidemic Spreading: A COVID-19 Case Study Content: In the recent COVID-19 pandemic, computer simulations are used to predict the evolution of the virus propagation and to evaluate the prospective effectiveness of non-pharmaceutical interventions. As such, the corresponding mathematical models and their simulations are central tools to guide political decision-making. Typically, ODE-based models are considered, in which fractions of infected and healthy individuals change deterministically and continuously over time. In this work, we translate an ODE-based COVID-19 spreading model from literature to a stochastic multi-agent system and use a contact network to mimic complex interaction structures. We observe a large dependency of the epidemic's dynamics on the structure of the underlying contact graph, which is not adequately captured by existing ODE-models. For instance, existence of super-spreaders leads to a higher infection peak but a lower death toll compared to interaction structures without super-spreaders. Overall, we observe that the interaction structure has a crucial impact on the spreading dynamics, which exceeds the effects of other parameters such as the basic reproduction number R0. We conclude that deterministic models fitted to COVID-19 outbreak data have limited predictive power or may even lead to wrong conclusions while stochastic models taking interaction structure into account offer different and probably more realistic epidemiological insights.", "qid": 14, "docid": "8m7n5r85", "rank": 19, "score": 10.735899925231934}, {"content": "Title: Clustering model for transmission of the SARS virus: application to epidemic control and risk assessment Content: Abstract We propose a new four state model for disease transmission and illustrate the model with data from the 2003 SARS epidemic in Hong Kong. The critical feature of this model is that the community is modelled as a small-world network of interconnected nodes. Each node is linked to a fixed number of immediate neighbors and a random number of geographically remote nodes. Transmission can only propagate between linked nodes. This model exhibits two features typical of SARS transmission: geographically localized outbreaks and \u201csuper-spreaders\u201d. Neither of these features are evident in standard susceptible-infected-removed models of disease transmission. Our analysis indicates that \u201csuper-spreaders\u201d may occur even if the infectiousness of all infected individuals is constant. Moreover, we find that nosocomial transmission in Hong Kong directly contributed to the severity of the outbreak and that by limiting individual exposure time to 3\u20135 days the extent of the SARS epidemic would have been minimal.", "qid": 14, "docid": "a95hh4yk", "rank": 20, "score": 10.715200424194336}, {"content": "Title: Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea Content: BACKGROUND. Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. We investigated the risk factors for MERS-CoV transmission. METHODS. Epidemiological reports were used to classify patients as nonspreaders, spreaders, or those associated with a super-spreading event (5 or more transmissions). Logistic regression analyses were used to evaluate the factors for MERS-CoV transmission. RESULTS. Compared to nonspreaders, spreaders exhibited a longer interval from symptom onset to isolation (7 days vs 3 days) and more frequent pre-isolation pneumonia diagnoses (68.2% vs 17.1%). Spreaders also exhibited higher values for pre-isolation contacts (149 vs 17.5), pre-isolation hospitalization (68.2% vs 16.5%), and emergency room (ER) visits (50% vs 7.3%). Spreaders exhibited lower cycle thresholds for the upE and ORF1a genes (22.7 vs 27.2 and 23.7 vs 27.9, respectively). In multivariate analysis, transmission was independently associated with the cycle threshold (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75\u20130.96) and pre-isolation hospitalization or ER visits (OR, 6.82; 95% CI, 2.06\u201322.84). The super-spreading events exhibited higher values for pre-isolation contacts (777 vs 78), pre-isolation ER visits (100% vs 35.3%), and doctor shopping (100% vs 47.1%) compared to non-super-spreading events. CONCLUSIONS. These findings indicate that transmission is determined by host infectivity and the number of contacts, whereas super-spreading events were determined by the number of contacts and hospital visits. These relationships highlight the importance of rapidly enforcing infection control measures to prevent outbreaks.", "qid": 14, "docid": "f0ny4ur5", "rank": 21, "score": 10.657500267028809}, {"content": "Title: The impact of super-spreaders in COVID-19: mapping genome variation worldwide Content: The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.", "qid": 14, "docid": "qw05apnf", "rank": 22, "score": 10.621700286865234}, {"content": "Title: Super spreader cohorts and covid-19 Content: A simple two-cohort SIR like model can explain the qualitative behaviour of the logarithmic derivative estimations of the covid-19 epidemic evolution as observed in several countries. The model consists of a general population in which the R_0 value is slightly below 1, but in which a super-spreading small subgroup with high R_0, coupled to the general population, is contaminating a significant fraction of the population. The epidemic starts to slow down when herd immunity is reached in this subgroup. The dynamics of this system is quite robust against non-pharmaceutical measures.", "qid": 14, "docid": "123i465d", "rank": 23, "score": 10.338500022888184}, {"content": "Title: Super-spreaders and the rate of transmission of the SARS virus Content: Abstract We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and \u201csuper-spreaders\u201d. Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) \u201csuper-spreaders\u201d may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3\u20135 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.", "qid": 14, "docid": "dqkjofw2", "rank": 24, "score": 10.334199905395508}, {"content": "Title: Characterizing super-spreading in microblog: An epidemic-based information propagation model Content: Abstract As the microblogging services are becoming more prosperous in everyday life for users on Online Social Networks (OSNs), it is more favorable for hot topics and breaking news to gain more attraction very soon than ever before, which are so-called \u201csuper-spreading events\u201d. In the information diffusion process of these super-spreading events, messages are passed on from one user to another and numerous individuals are influenced by a relatively small portion of users, a.k.a. super-spreaders. Acquiring an awareness of super-spreading phenomena and an understanding of patterns of wide-ranged information propagations benefits several social media data mining tasks, such as hot topic detection, predictions of information propagation, harmful information monitoring and intervention. Taking into account that super-spreading in both information diffusion and spread of a contagious disease are analogous, in this study, we build a parameterized model, the SAIR model, based on well-known epidemic models to characterize super-spreading phenomenon in tweet information propagation accompanied with super-spreaders. For the purpose of modeling information diffusion, empirical observations on a real-world Weibo dataset are statistically carried out. Both the steady-state analysis on the equilibrium and the validation on real-world Weibo dataset of the proposed model are conducted. The case study that validates the proposed model shows that the SAIR model is much more promising than the conventional SIR model in characterizing a super-spreading event of information propagation. In addition, numerical simulations are carried out and discussed to discover how sensitively the parameters affect the information propagation process.", "qid": 14, "docid": "av8ww9fd", "rank": 25, "score": 10.28950023651123}, {"content": "Title: Minimising lockdown periods for regional elimination of covid-19 Content: Some nations have the option of pursuing a policy of complete elimination of covid-19 instead of a policy of \"flattening the curve\" so that the load the dis- ease places on medical facilities is bearable. A policy of elimination requires a rather onerous \"lockdown\". As the goal of elimination is approached, it is therefore important that there be an informed trade-off between the risk of disease re-emergence and the duration of the \"lockdown\". Here it is shown that an important factor in assessing this trade-off, is the distribution of secondary cases, not just the expected value of this distribution, R0 . It is shown that a distribution in which \"super-spreaders\" are more prominent in the epidemiology, allows for an earlier release from \"lockdown\" with reasonable safety despite some probability of asymptomatic cases. There is some evidence to support such a distribution for covid-19. Analytical calculations and simulations show that once there is only one recognised case in some subregion, release from \"lockdown\" will be reasonably safe after just one or two further incubation periods.", "qid": 14, "docid": "1ir2ptuj", "rank": 26, "score": 10.175000190734863}, {"content": "Title: Agent-Based Modeling for Super-Spreading Events: A Case Study of MERS-CoV Transmission Dynamics in the Republic of Korea Content: Super-spreading events have been observed in the transmission dynamics of many infectious diseases. The 2015 MERS-CoV outbreak in the Republic of Korea has also shown super-spreading events with a significantly high level of heterogeneity in generating secondary cases. It becomes critical to understand the mechanism for this high level of heterogeneity to develop effective intervention strategies and preventive plans for future emerging infectious diseases. In this regard, agent-based modeling is a useful tool for incorporating individual heterogeneity into the epidemic model. In the present work, a stochastic agent-based framework is developed in order to understand the underlying mechanism of heterogeneity. Clinical (i.e., an infectivity level) and social or environmental (i.e., a contact level) heterogeneity are modeled. These factors are incorporated in the transmission rate functions under assumptions that super-spreaders have stronger transmission and/or higher links. Our agent-based model has employed real MERS-CoV epidemic features based on the 2015 MERS-CoV epidemiological data. Monte Carlo simulations are carried out under various epidemic scenarios. Our findings highlight the roles of super-spreaders in a high level of heterogeneity, underscoring that the number of contacts combined with a higher level of infectivity are the most critical factors for substantial heterogeneity in generating secondary cases of the 2015 MERS-CoV transmission.", "qid": 14, "docid": "2wc1bxi1", "rank": 27, "score": 10.07409954071045}, {"content": "Title: Identification of a super-spreading chain of transmission associated with COVID-19 Content: Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.", "qid": 14, "docid": "yp38t4yb", "rank": 28, "score": 10.006699562072754}, {"content": "Title: Children are not COVID-19 super spreaders: time to go back to school. Content:", "qid": 14, "docid": "m005jyta", "rank": 29, "score": 9.97599983215332}, {"content": "Title: Chest tube with air leaks is a potential \u201csuper spreader\u201d of COVID-19 Content:", "qid": 14, "docid": "y42o6exe", "rank": 30, "score": 9.975998878479004}, {"content": "Title: Chest tube with air leaks is a potential \"super spreader\" of COVID-19 Content:", "qid": 14, "docid": "z19xdrxu", "rank": 31, "score": 9.975997924804688}, {"content": "Title: Children are not COVID-19 super spreaders: time to go back to school Content:", "qid": 14, "docid": "zy1byu51", "rank": 32, "score": 9.975996971130371}, {"content": "Title: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China Content: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54\u20130.84) and 0.25 (95% CI: 0.13\u20130.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "qid": 14, "docid": "3v4sedfo", "rank": 33, "score": 9.954099655151367}, {"content": "Title: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China Content: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54-0.84) and 0.25 (95% CI: 0.13-0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "qid": 14, "docid": "uo7ixk9r", "rank": 34, "score": 9.95409870147705}, {"content": "Title: Pausing super spreader events for COVID-19 mitigation: International Hajj pilgrimage cancellation Content:", "qid": 14, "docid": "k6ijng66", "rank": 35, "score": 9.93850040435791}, {"content": "Title: [Investigation of a cluster epidemic of COVID-19 in Ningbo]. Content: Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.", "qid": 14, "docid": "hsgx534y", "rank": 36, "score": 9.770099639892578}, {"content": "Title: [Investigation of a cluster epidemic of COVID-19 in Ningbo] Content: Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.", "qid": 14, "docid": "x9c2ymra", "rank": 37, "score": 9.770098686218262}, {"content": "Title: Using models to identify routes of nosocomial infection: a large hospital outbreak of SARS in Hong Kong. Content: Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002-2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.", "qid": 14, "docid": "9mhcr9h4", "rank": 38, "score": 9.742799758911133}, {"content": "Title: Precision public health to inhibit the contagion of disease and move toward a future in which microbes spread health Content: Antimicrobial resistance continues to outpace the development of new chemotherapeutics. Novel pathogens continue to evolve and emerge. Public health innovation has the potential to open a new front in the war of \u201cour wits against their genes\u201d (Joshua Lederberg). Dense sampling coupled to next generation sequencing can increase the spatial and temporal resolution of microbial characterization while sensor technologies precisely map physical parameters relevant to microbial survival and spread. Microbial, physical, and epidemiological big data could be combined to improve prospective risk identification. However, applied in the wrong way, these approaches may not realize their maximum potential benefits and could even do harm. Minimizing microbial-human interactions would be a mistake. There is evidence that microbes previously thought of at best \u201cbenign\u201d may actually enhance human health. Benign and health-promoting microbiomes may, or may not, spread via mechanisms similar to pathogens. Infectious vaccines are approaching readiness to make enhanced contributions to herd immunity. The rigorously defined nature of infectious vaccines contrasts with indigenous \u201cbenign or health-promoting microbiomes\u201d but they may converge. A \u201cmicrobial Neolithic revolution\u201d is a possible future in which human microbial-associations are understood and managed analogously to the macro-agriculture of plants and animals. Tradeoffs need to be framed in order to understand health-promoting potentials of benign, and/or health-promoting microbiomes and infectious vaccines while also discouraging pathogens. Super-spreaders are currently defined as individuals who play an outsized role in the contagion of infectious disease. A key unanswered question is whether the super-spreader concept may apply similarly to health-promoting microbes. The complex interactions of individual rights, community health, pathogen contagion, the spread of benign, and of health-promoting microbiomes including infectious vaccines require study. Advancing the detailed understanding of heterogeneity in microbial spread is very likely to yield important insights relevant to public health.", "qid": 14, "docid": "75pu449b", "rank": 39, "score": 9.61870002746582}, {"content": "Title: Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan Content: We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.", "qid": 14, "docid": "mtoaz6vx", "rank": 40, "score": 9.577199935913086}, {"content": "Title: Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan Content: Abstract We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.", "qid": 14, "docid": "h2gwzypy", "rank": 41, "score": 9.517900466918945}, {"content": "Title: Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China Content: Background: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics including heterogeneity is of vital importance for prediction and intervention of future epidemics. In addition, transmission heterogeneity usually envokes super spreading events (SSEs) where certain individuals infect large numbers of secondary cases. Till now, studies of transmission heterogeneity of COVID-19 and its underlying reason are far from reaching an agreement. MethodsWe collected information of all infected cases between January 21 and February 26, 2020 from official public sources in Tianjin, a metropolis of China. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k which characterized the transmission potential and heterogeneity, respectively. Furthermore, we studied the SSE in Tianjin outbreak and evaluated the effect of control measures undertaken by local government based on the heterogeneous model. Results: A total of 135 confirmed cases (including 34 imported cases and 101 local infections) in Tianjin by February 26th 2020 entered the study. We grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of 4 generations. The estimated reproduction number R was at 0.67 (95%CI: 0.54[~]0.84), and the dispersion parameter k was at 0.25 (95% CI: 0.13[~]0.88). A super spreader causing six infections in Tianjin, was identified. In addition, our simulation results showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since January 28th. Conclusions: Our analysis suggested that the transmission of COVID-19 was subcritical but with significant heterogeneity and may incur SSE. More efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors, which is important for developing targeted measures to curb the pandemic.", "qid": 14, "docid": "uicvudil", "rank": 42, "score": 9.412400245666504}, {"content": "Title: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Content: Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any \u201dnormal\u201d post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.", "qid": 14, "docid": "iwkuwnun", "rank": 43, "score": 9.392900466918945}, {"content": "Title: Accounting for super-spreading gives the basic reproduction number R0 of COVID-19 that is higher than initially estimated Content: Transmission of infectious diseases is characterized by the basic reproduction number R0, a metric used to assess the threat posed by an outbreak and inform proportionate preventive decision-making. Based on individual case reports from the initial stage of the coronavirus disease 2019 epidemic, R0 is often estimated to range between 2 and 4. In this report, we show that a SEIR model that properly accounts for the distribution of the incubation period suggests that R0 lie in the range 4.4 - 11.7. This estimate is based on the doubling time observed in the near-exponential phases of the epidemic spread in China, United States, and six European countries. To support our empirical estimation, we analyze stochastic trajectories of the SEIR model showing that in the presence of super-spreaders the calculations based on individual cases reported during the initial phase of the outbreak systematically overestimate the doubling time and thus underestimate the actual value of R0.", "qid": 14, "docid": "3ruxk6u2", "rank": 44, "score": 9.371199607849121}, {"content": "Title: ACE 2 Coding Variants: A Potential X-linked Risk Factor for COVID-19 Disease Content: Viral genetic variants are widely known to influence disease progression among infected humans. Given the recent and rapid emergence of pandemic SARS-CoV-2 infection, the cause of COVID-19 disease, viral protein variants have attracted research interest. However, little has yet been written about genetic risk factors among human hosts. Human genetic variation has proven to affect disease progression and outcome for important diseases such as HIV infection and malaria infestation. The fact that the human ACE2 protein is encoded on the X chromosome means that males who carry rare ACE2 coding variants will express those variants in all ACE2-expressing cells, whereas females will typically express those variants in a mosaic distribution determined by early X-inactivation events. This sex-based difference in ACE2 expression has unique implications for epidemiological studies designed to assess host genetic factors influencing progression from asymptomatic SARS-coV-2 infection to COVID-19. Here we present theoretical modelling of rare ACE2 coding variants documented to occur naturally in several human superpopulations and subpopulations, and show that rare variants predicted to affect the binding of ACE2 to the SARS-CoV-2 spike protein exist in people. Though the rs4646116 (p.Lys26Arg) allele is found in 1 in 70 Ashkenazi Jewish males, and in 1 in 172 non-Finnish European males, this allele is found at higher frequencies in females. Furthermore, the class of missense ACE2 alleles predicted to affect SARS-CoV-2 binding are found in aggregate among 1.43% and 2.16% of Ashkenazi males and females, respectively, as well as in 0.58% and 1.24% of European males and females outside of Finland. These alleles are rarer in other population groups, and almost absent from East Asians genotyped to date. Though we are aware that full genome-wide and exome-wide sequencing studies may ultimately be required to assess human genetic susceptibility to SARS-CoV-2 fully, we argue on the basis of strong prior probabilities that genotyping of this class of alleles is justified in cases of atypical SARS-CoV-2 diseases, such as asymptomatic super-spreaders (if any are identified), and in neonatal/paediatric-onset COVID-19 disease. Even relatively rare susceptibility factors (1% or fewer carriers) may become quantitatively important in the context of hundreds of thousands of infections. A small number of asymptomatic carriers, or a small number of super-spreaders, or a small segment of the population that is disproportionately likely to require intensive care, can magnify the medical, social and economic impacts of a pandemic of this size. The speed of the pandemic and the large number of affected cases worldwide justify efforts to identify all possible risk factors for adverse outcomes, including efforts to identify genetic susceptibility factors in human hosts.", "qid": 14, "docid": "05w8tv8x", "rank": 45, "score": 9.35260009765625}, {"content": "Title: [Epidemiological characteristics of severe acute respiratory syndrome in Tianjin and the assessment of effectiveness on measures of control]. Content: OBJECTIVE To analyze the epidemiologic characteristics of severe acute respiratory syndrome (SARS) and to evaluate the effectiveness on its major control measures in Tianjn. METHODS Adopting two case reports 1 and 2, designed by the Tianjin Centers for Disease Control and Prevention to develop a unified case-tracing table including the map of the distribution of close contacts to SARS patients. With those methods, investigation on patients and their close contacts at hospital wards, families, communities and institutions of the patients were carried out. RESULTS From April 13 through May 8, 2003, there were 175 SARS cases including imported ones, were identified with an incidence rate of 1.9 cases per 100,000. Among them, 14 died with a fatality of 8.0%. The whole process of epidemic in Tianjin was less than one month with the following features: (1) 93.7% of the total SARS cases in Tianjin were directly or indirectly transmitted by a super-spreader. (2) 68.6% of the total SARS patients were concentrated in 3 hospitals A, B and C which was menifastated in 'clustering'. Through study on the rest of the SARS patients, results showed that 16.8% of them were transmitted through family close contact and 2.3% due to contact to colleagues. However, 12.6% of the patients were not able to show evidence that they had any contact to a diagnosed SARS patient. At the early stage of the epidemic, a number of medical practitioners were infected, taking up 38.2% of the total SARS cases. Among the total number of 1 975 medical workers who participated in the SARS medical cares and treatments, 3.4% of them got infected. During the outbreak, all index cases and chains of transmission seemed to be clear, with only 3 patients not able to be traced for the source of infection, taking up 2% of the total SARS patients in Tianjin. Among the 10 index cases, only the super spreader and another one index case transmitted the virus to their contacts but the rest of index cases did not cause any secondary infection. CONCLUSION Though SARS is clinically severe and can be spreaded quickly, the epidemic can be under control within a short period of time if chains of SARS transmission are broken down and effective measures as isolation and quarantine against patients as well as underscoring awareness among the publics in a scientific way, being carried out.", "qid": 14, "docid": "lf2mfqgb", "rank": 46, "score": 9.186300277709961}, {"content": "Title: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries Content: A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "qid": 14, "docid": "3uzsx715", "rank": 47, "score": 9.175100326538086}, {"content": "Title: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries. Content: A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "qid": 14, "docid": "4zyfc0y4", "rank": 48, "score": 9.17509937286377}, {"content": "Title: A note on community-detection (Kemeny) based testing for COVID-19 Content: The Kemeny constant of a graph can be used to identify and analyse bridges between communities in a graph. Testing, tracking and tracing abilities have been identified as pivotal in helping countries to safely reopen activities after the first wave of the COVID-19 virus. Tracing techniques aim at reconstructing past history of contacts, but can face practical limits in an exponential growth of either testing or overly conservative quarantining. We show how this application of graph theory can be conveniently used to efficiently intercept new virus outbreaks, when they are still in their early stage. Simulations provide promising results in early identification and blocking of possible\"super-spreader links that transmit disease between different communities.", "qid": 14, "docid": "eofrf2em", "rank": 49, "score": 9.017600059509277}, {"content": "Title: Airflow as a Possible Transmission Route of Middle East Respiratory Syndrome at an Initial Outbreak Hospital in Korea Content: In this study, the results of an airflow investigation conducted on 7 June 2015 as part of a series of epidemiologic investigations at Pyeongtaek St. Mary\u2019s Hospital, South Korea, were investigated. The study involved 38 individuals who were infected directly and indirectly with Middle East Respiratory Syndrome (MERS), by a super-spreader patient. Tracer gas experiments conducted on the eighth floor, where the initial patient was hospitalized, confirmed that the tracer gas spread to adjacent patient rooms and rooms across corridors. In particular, the experiment with an external wind direction and speed similar to those during the hospitalization of the initial patient revealed that the air change rate was 17\u201320 air changes per hour (ACH), with air introduced through the window in the room of the infected patient (room 8104). The tracer gas concentration of room 8110, which was the farthest room, was 7.56% of room 8104, indicating that a high concentration of gas has spread from room 8104 to rooms across the corridor. In contrast, the tracer gas was barely detected in a maternity ward to the south of room 8104, where there was no secondary infected patient. Moreover, MERS is known to spread mainly by droplets through close contact, but long-distance dispersion is probable in certain environments, such as that of a super-spreader patient hospitalized in a room without ventilation, hospitals with a central corridor type, and indoor airflow dispersion due to external wind.", "qid": 14, "docid": "mz5gdb59", "rank": 50, "score": 8.888799667358398}, {"content": "Title: Transmission characteristics of the COVID-19 outbreak in China: a study driven by data Content: The COVID-19 outbreak has been a serious public health threat worldwide. We use individually documented case descriptions of COVID-19 from China (excluding Hubei Province) to estimate the distributions of the generation time, incubation period, and periods from symptom onset to isolation and to diagnosis. The recommended 14-day quarantine period may lead to a 6.7% failure for quarantine. We recommend a 22-day quarantine period. The mean generation time is 3.3 days and the mean incubation period is 7.2 days. It took 3.7 days to isolate and 6.6 days to diagnose a patient after his/her symptom onset. Patients may become infectious on average 3.9 days before showing major symptoms. This makes contact tracing and quarantine ineffective. The basic reproduction number is estimated to be 1.54 with contact tracing, quarantine and isolation, mostly driven by super spreaders.", "qid": 14, "docid": "px0twvhs", "rank": 51, "score": 8.862099647521973}, {"content": "Title: Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks Content: The basic reproductive number (R(0)) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R(0) cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number R(t) can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, R(t) may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (R(j)) and a summarized indicator for population-level time-varying reproductive number (R(t)). Data from the five most severe dengue outbreaks in southern Taiwan from 1998\u20132015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest R(j) during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.", "qid": 14, "docid": "oen0ycsr", "rank": 52, "score": 8.826199531555176}, {"content": "Title: Modelling suggests blood group incompatibility may substantially reduce SARS-CoV-2 transmission Content: Several independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. Here, I model a scenario in which ABO transfusion incompatibility reduces the chance of a patient transmitting the virus to an incompatible recipient. Comparison of model outputs to published data on COVID-19 prevalence indicates that if this scenario holds true, ABO incompatibility may reduce virus transmissibility by 60% or more. Paradoxically, however, targeted vaccination of either high-susceptibility type A or \"super-spreader\" type O individuals is less effective than random vaccination at blocking community spread of the virus. Instead, the key is to maintain blood type diversity amongst the remaining susceptible individuals. I stress that these results illustrate a theoretical model of ABO blood group interaction with virus transmission and require confirmation by observation.", "qid": 14, "docid": "rbtgsoa1", "rank": 53, "score": 8.800000190734863}, {"content": "Title: The correspondence between the structure of the terrestrial mobility network and the emergence of COVID-19 in Brazil Content: The inter-cities mobility network is of great importance in understanding outbreaks, especially in Brazil, a continental-dimension country. Grounded on the complex networks approach, cities are here represented as nodes and the flows as weighted edges - these geographical graphs, (geo)graphs, are handled in a Geographical Information System. We adopt the IBGE database from 2016, which contains the weekly flow of people between cities in terrestrial vehicles. The present work aims to investigate the correspondences of the networks' measures, like strength, degree, and betweenness with the emergence of cities with confirmed cases of COVID-19 in Brazil, and special attention is given to the state of Sao Paulo. We show that the results are better when certain thresholds are applied to the networks' flows to neglect the lowest-frequency travels. The correspondences presented statistical significance for most measures up to a certain period. Until the end of April, the best matchings are with the strength measure (total flow related to a node/city) under a high flow threshold in the Sao Paulo state, when the most connected cities are reached. After this stage, the lower thresholds become more suitable, indicating a possible signature of the outbreak interiorization process. Surprisingly, some countryside cities such as Campina Grande (state of Paraiba), Feira de Santana (state of Bahia), and Caruaru (state of Pernambuco) have higher strengths than some states' capitals. Furthermore, some cities from the Sao Paulo state such as Presidente Prudente and Ribeirao Preto are captured in the top-rank positions of all the analyzed network measures under different flow thresholds. Their importance in mobility is crucial and they are potential super spreaders like the states' capitals. Our analysis offers additional tools for understanding and decision support to inter-cities mobility interventions regarding the SARS-CoV-2 and other epidemics.", "qid": 14, "docid": "cxiac4pm", "rank": 54, "score": 8.71780014038086}, {"content": "Title: Testing for COVID-19: willful ignorance or selfless behavior? Content: Widespread testing is key to controlling the spread of COVID-19. But should we worry about self-selection bias in the testing? The recent literature on willful ignorance says we should \u2013 people often avoid health information. In the context of COVID-19, such willful ignorance can bias testing data. Furthermore, willful ignorance often arises when selfish wants conflict with social benefits, which might be particularly likely for potential \u2018super-spreaders\u2019 \u2013 people with many social interactions \u2013 given people who test positive are urged to self-isolate for two weeks. We design a survey in which participants (n = 897) choose whether to take a costless COVID-19 test. We find that 70% would take a test. Surprisingly, the people most likely to widely spread COVID-19 \u2013 the extraverts, others who meet more people in their daily lives and younger people \u2013 are the most willing to take a test. People's ability to financially or emotionally sustain self-isolation does not matter to their decision. We conclude that people are selfless in their decision to test for COVID-19. Our results are encouraging \u2013 they imply that COVOD-19 testing may succeed in targeting those who generate the largest social benefits from self-isolation if infected, which strengthens the case for widespread testing.", "qid": 14, "docid": "oyfx3ij5", "rank": 55, "score": 8.628999710083008}, {"content": "Title: Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus Content: Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non\u2013consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing. A total of 35 specimens from 24 patients (including a super-spreader) were sequenced to detect and analyze variants displaying intrapatient heterogeneity. Based on the analysis of non\u2013consensus sequences, we demonstrated the intrapatient heterogeneity of MERS-CoVs, with the highest level in the super-spreader specimen. The heterogeneity could be transmitted in a close association with variation in the consensus sequences, suggesting the occurrence of multiple MERS-CoV infections. Analysis of intrapatient heterogeneity revealed a relationship between D510G and I529T mutations in the receptor-binding domain (RBD) of the viral spike glycoprotein. These two mutations have been reported to reduce the affinity of the RBD for human CD26. Notably, although the frequency of both D510G and I529T varied greatly among specimens, the combined frequency of the single mutants was consistently high (87.7% \u00b1 1.9% on average). Concurrently, the frequency of occurrence of the wild type at the two positions was only 6.5% \u00b1 1.7% on average, supporting the hypothesis that selection pressure exerted by the host immune response played a critical role in shaping genetic variants and their interaction in human MERS-CoVs during the outbreak.", "qid": 14, "docid": "xgp2vx6o", "rank": 56, "score": 8.619799613952637}, {"content": "Title: System Dynamics Modeling of Within-Host Viral Kinetics of Coronavirus (SARS CoV-2) Content: Mathematical models are being used extensively in the study of SARS-CoV-2 transmission dynamics, becoming an essential tool for decision making concerning disease control. It is now required to understand the mechanisms involved in the interaction between the virus and the immune response effector cells, both innate and adaptive, in order to support lines of research related to the use of drugs, production of protective antibodies and of course, vaccines against SARS-CoV-2. The present study, using a system dynamic approach, hypothesizes over the conditions that characterize the fraction of the population which get infected by SARS-CoV-2 as the asymptomatic patients, the mild symptomatic, acute symptomatic, and also super-spreaders, in terms of innate immune response, the initial virus load, the virus burden with shedding events, and the cytokine levels.", "qid": 14, "docid": "q1p6h532", "rank": 57, "score": 8.601300239562988}, {"content": "Title: Predicting Super Spreading Events during the 2003 Severe Acute Respiratory Syndrome Epidemics in Hong Kong and Singapore Content: One of the intriguing characteristics of the 2003 severe acute respiratory syndrome (SARS) epidemics was the occurrence of super spreading events (SSEs). Here, the authors report the results of identifying the occurrence of SSEs in the Hong Kong and Singapore epidemics using mathematical and statistical analysis. Their predicted occurrence of SSEs agreed well with the reported occurrence of all seven super spreaders in the two cities. Additional unidentified SSEs were also found to exist. It was found that 71.1% and 74.8% of the infections were attributable to SSEs in Hong Kong and Singapore, respectively. There also seemed to be \u201csynchronized\u201d occurrences of infection peaks in both the community and the hospitals in Hong Kong. The results strongly suggested that the infection did not depend on the total number of symptomatic cases, with only a very small proportion of symptomatic individuals being shown to be infectious (i.e., able to infect other individuals). The authors found that the daily infection rate did not correlate with the daily total number of symptomatic cases but with the daily number of symptomatic cases who were not admitted to a hospital within 4 days of the onset of symptoms.", "qid": 14, "docid": "axns3ukm", "rank": 58, "score": 8.573699951171875}, {"content": "Title: Multi-chain Fudan-CCDC model for COVID-19 -- a revisit to Singapore's case Content: Background: COVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense worldwide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. Methods: We propose the multi-chain Fudan-CCDC model based on the original single-chain model in [8] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify parameters of models by minimizing the penalty function. Results: The numerical simulation results exhibit the multi-chain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of 25% fluctuation from simulation results. It is predicted by multi-chain models that Singapore are experiencing a nonnegligible risk of explosive outbreak, thus stronger measures are urgently needed to contain the epidemic. Conclusion: The multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data in those countries where the single-chain model shows deviation from the data.", "qid": 14, "docid": "etnf4i8v", "rank": 59, "score": 8.48960018157959}, {"content": "Title: No evidence of viral polymorphisms associated with Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS). Content: Generally, children and teenagers do not become seriously ill with COVID-19. However, in countries with high rates of coronavirus disease, children with the syndrome COVID-19 associated inflammation syndrome referred to as PIMS-TS have been reported. Similarities noted between SARS-CoV-2 Spike protein sequences and those of other super antigens has prompted the suggestion that this might be the mechanism by SARS-CoV-ST triggers PIMS-TS. It has also been suggested that the D614G variant found more commonly in the US and across European countries may explain why PIMS-TS appears to be common in these countries. Here we analysed viral sequences from 13 paediatric COVID-19 patients of whom five were diagnosed with PIMS-TS. This is the first characterisation of viruses from PIMS-TS patients. In contrast to what has been hypothesised, we found no evidence of unique sequences associated with the viruses from PIMS-TS patients.", "qid": 14, "docid": "cuntxa6e", "rank": 60, "score": 8.47760009765625}, {"content": "Title: Clinical and Transmission Characteristics of Covid-19 - A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department Content: The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential \"super spreader\" may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.", "qid": 14, "docid": "xwqxji63", "rank": 61, "score": 8.459500312805176}, {"content": "Title: Clinical and Transmission Characteristics of Covid-19 \u2014 A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department Content: The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential \u201csuper spreader\u201d may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.", "qid": 14, "docid": "z2q063sa", "rank": 62, "score": 8.45949935913086}, {"content": "Title: Topological dynamics of the 2015 South Korea MERS-CoV spread-on-contact networks Content: Network analysis to examine infectious contact relations provides an important means to uncover the topologies of individual infectious contact networks. This study aims to investigate the spread of diseases among individuals over contact networks by exploring the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. We present several distinct features of MERS transmission by employing a comprehensive approach in network research to examine both the traced relationship matrix of infected individuals and their bipartite transmission routes among healthcare facilities visited for treatment. The results indicate that a few super-spreaders were more likely to hold certain structural advantages by linking to an exceptional number of other individuals, causing several ongoing transmission events in neighbourhoods without the aid of any intermediary. Thus, the infectious contact network exhibited small-world dynamics characterised by locally clustered contacts exposed to transmission paths via short path lengths. In addition, nosocomial infection analysis shows the pattern of a common-source outbreak followed by secondary person-to-person transmission of the disease. Based on the results, we suggest policy implications related to the redesign of prevention and control strategies against the spread of epidemics.", "qid": 14, "docid": "a5baie4z", "rank": 63, "score": 8.342499732971191}, {"content": "Title: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China Content: IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.", "qid": 14, "docid": "b10yokyu", "rank": 64, "score": 8.285799980163574}, {"content": "Title: A study of the probable transmission routes of MERS\u2010CoV during the first hospital outbreak in the Republic of Korea Content: Infections caused by the Middle East respiratory syndrome coronavirus (MERS\u2010CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS\u2010CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi\u2010agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long\u2010range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi\u2010agent modeling framework. Least\u2010squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super\u2010spreader, our model simulations suggested that MERS\u2010CoV probably spread via the long\u2010range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long\u2010range airborne and close contact route.", "qid": 14, "docid": "4nd5wzrm", "rank": 65, "score": 8.114700317382812}, {"content": "Title: Ultrametric model for covid-19 dynamics: an attempt to explain slow approaching herd immunity in Sweden Content: We present a mathematical model of infection dynamics that might explain slower approaching the herd immunity during the covid-19 epidemy in Sweden than it was predicted by a variety of other models; see graphs Fig. 2. The new model takes into account the hierarchic structure of social clusters in the human society. We apply the well developed theory of random walk on the energy landscapes represented mathematically with ultrametric spaces. This theory was created for applications to spin glasses and protein dynamics. To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider linearly increasing (with respect to hierarchy's levels) barriers. This structure of barriers matches with a rather soft regulations imposed in Sweden in March 2020. In this model, the infection spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This model's feature matches with the real situation during the covid-19 epidemy, with its cluster spreading structure. Clusters need not be determined solely geographically, they are based on a number of hierarchically ordered social coordinates. The model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. In particular, our model describes such a specialty of spread of covid-19 virus as the presence of \"super-spreaders\" who by performing a kind of random walk on a hierarchic landscape of social clusters spreads infection. In future, this model will be completed by adding the SIR-type counterpart. But, the latter is not a specialty of covid-19 spreading.", "qid": 14, "docid": "njypqq2c", "rank": 66, "score": 8.06659984588623}, {"content": "Title: Severe acute respiratory syndrome--Singapore, 2003. Content: The Singapore Ministry of Health (MOH), with assistance from the World Health Organization (WHO), has been investigating an outbreak of severe acute respiratory syndrome (SARS). This is a novel condition caused by the SARS-associated coronavirus (SARS-CoV) and is characterized by both an atypical pneumonia and efficient nosocomial transmission. This report summarizes epidemiologic features of this outbreak in Singapore, including the influence of super spreaders and the national prevention and control strategy.", "qid": 14, "docid": "c48gl27o", "rank": 67, "score": 7.941699981689453}, {"content": "Title: Epidemiology and Clinical Features of Coronavirus disease 2019 in Children Content: Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.", "qid": 14, "docid": "h2cm3cge", "rank": 68, "score": 7.915299892425537}, {"content": "Title: Generality of endemic prevalence formulae Content: Abstract In simple infection models, the susceptible proportion s * in endemic equilibrium is related to the basic reproduction number R 0 by s * = 1 / R 0 . We investigate the extent to which this relationship remains valid under more realistic modelling assumptions. In particular, we relax the biologically implausible assumptions that individuals\u2019 lifetimes and infectious periods follow exponential distributions; allow a general recruitment process; allow for multiple stages of infection; and consider extension to a multigroup model in which the groups may represent, for instance, spatial heterogeneity, or the existence of super-spreaders. For a homogeneous population, we find that: (i) the susceptible proportion is s * = 1 / R 0 e , where R 0 e is a modified reproduction number, equal to R 0 only in certain circumstances; (ii) the proportions of the population in each stage of infection are proportional to the expected time spent by an infected individual in that stage before recovery or death. We demonstrate robustness of the formula s * = 1 / R 0 for many human infections by noting conditions under which R 0 e is approximately equal to R 0, while pointing out other circumstances under which this approximation fails. For heterogeneous populations, the formula s * = 1 / R 0 does not hold in general, but we are able to exhibit symmetry conditions under which it is valid.", "qid": 14, "docid": "gmpsniqt", "rank": 69, "score": 7.884399890899658}, {"content": "Title: Relationship between perception and anxiety about COVID-19 infection and risk behaviors for spreading infection: A national survey in Japan Content: BACKGROUND: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of \u201cpossible super spreaders\u201d, suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies. METHODS: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020. FINDINGS: Thirteen-point-three percent of the participants rated \u201c1\u201d on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses. INTERPRETATION: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic. FUNDING: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.", "qid": 14, "docid": "5nkoybui", "rank": 70, "score": 7.872700214385986}, {"content": "Title: Study of Non-Pharmacological Interventions on COVID-19 Spread Content: COVID-19 disease has emerged as one of the life threatening threat to the society. It is caused by a novel beta coronavirus. It began as unidentified pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. No vaccine has been produced till now. Mathematical models are used to study impact of different measures used to decrease pandemic. Mathematical models have been designed to estimate the numbers of spreaders in different scenarios in the present manuscript. In the present manuscript, three different mathematical models have been proposed with different scenarios such as screening, quarantine and NPIs for estimating number of virus spreaders. the analysis shows that the numbers of COVID-19 patients will be more without screening the peoples coming from other countries. Since, every people suffering with COVID-19 disease are spreaders. The screening and quarantine with NPIs have been implemented to study their impact on the spreaders. It has been found that NPI measures are able to reduce number of spreaders. The NPI measures reduces the growth of the spread function and providing decision makers more time to prepare with in dealing of the disease.", "qid": 14, "docid": "1obd7mq8", "rank": 71, "score": 7.8155999183654785}, {"content": "Title: Sensitivity of commercial Anti-SARS-CoV-2 serological assays in a high-prevalence setting Content: We analysed SARS-CoV-2 specific antibody responses in 42 social and working contacts of a super-spreader from the Heinsberg area in Germany. Consistent with a high-prevalence setting 26 individuals had SARS-CoV-2 antibodies determined by in-house neutralisation testing. These results were compared with four commercial assays, suggesting limited sensitivity of the assays in such a high-prevalence setting. Although SARS-CoV-2 nucleocapsid restricted tests showed a better sensitivity, spike based assays had a stronger correlation with neutralisation capacity.", "qid": 14, "docid": "k2djlq01", "rank": 72, "score": 7.700099945068359}, {"content": "Title: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics Content: In December 2019, a new virus (initially called 'Novel Coronavirus 2019-nCoV' and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China's massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.", "qid": 14, "docid": "oe6daiwx", "rank": 73, "score": 7.690100193023682}, {"content": "Title: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics Content: In December 2019, a new virus (initially called \u2018Novel Coronavirus 2019-nCoV\u2019 and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China\u2019s massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.", "qid": 14, "docid": "sjrnu3f3", "rank": 74, "score": 7.690099239349365}, {"content": "Title: Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak Content: Abstract To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447\u2013178.145; P < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402\u201313.761; P = 0.011) were significantly associated with MERS-CoV infection.", "qid": 14, "docid": "bnh65bqg", "rank": 75, "score": 7.597499847412109}, {"content": "Title: Plausible models for propagation of the SARS virus Content: Using daily infection data for Hong Kong we explore the validity of a variety of models of disease propagation when applied to the SARS epidemic. Surrogate data methods show that simple random models are insufficient and that the standard epidemic susceptible-infected-removed model does not fully account for the underlying variability in the observed data. As an alternative, we consider a more complex small world network model and show that such a structure can be applied to reliably produce simulations quantitative similar to the true data. The small world network model not only captures the apparently random fluctuation in the reported data, but can also reproduces mini-outbreaks such as those caused by so-called ``super-spreaders'' and in the Hong Kong housing estate Amoy Gardens.", "qid": 14, "docid": "wj7ik9qv", "rank": 76, "score": 7.497499942779541}, {"content": "Title: A systematic review of Anakinra, Tocilizumab, Sarilumab and Siltuximab for coronavirus-related infections Content: Background There is accumulating evidence for an overly activated immune response characterised by the release of pro-inflammatory cytokines in severe Covid-19. Suppression of the inflammatory response with immunomodulatory therapies may be a potential therapeutic strategy. We systematically review and assess the effectiveness of specific interleukin-1 and -6 inhibitors for the treatment of coronavirus-related infections. Methods Electronic databases, pre-print servers and clinical trial registries were searched to identify current and ongoing studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of Covid-19 and other coronavirus related super infections. The co-primary outcome was time to hospital discharge (days) and severity on an ordinal scale measured at day 15. Results Five retrospective studies (tocilizumab, two case series and two case reports; siltuximab, one case series) were shortlisted for inclusion, totalling 59 patients. All studies had a moderate or high risk of bias, with multiple limitations. Insufficient data and inter-study heterogeneity prevented meta-analysis. Primary outcomes were inconsistently reported but suggest many patients experienced an improvement in status seven days following therapy. The case fatality ratio (CFR) of patients with severe Covid-19 included in our review was 6.8%, a figure substantially lower than that estimated in non-interventional case series. Of the studies measuring IL-6, all reported elevated baseline levels. Twenty-five ongoing registered clinical trials exploring immunomodulatory agents in Covid-19 were identified, although inconsistency in participants and endpoints are noted. Conclusion Inhibition of IL-6 with tocilizumab and siltuximab requires further evaluation in managing the assumed hyperinflammatory response associated with severe Covid-19. These early data are considered hypothesis generating and justify the need for well-designed randomised clinical studies.", "qid": 14, "docid": "t7kjh9yr", "rank": 77, "score": 7.311299800872803}, {"content": "Title: Contact tracing and disease control. Content: Contact tracing, followed by treatment or isolation, is a key control measure in the battle against infectious diseases. It is an extreme form of locally targeted control, and as such has the potential to be highly efficient when dealing with low numbers of cases. For this reason it is frequently used to combat sexually transmitted diseases and new invading pathogens. Accurate modelling of contact tracing requires explicit information about the disease-transmission pathways from each individual, and hence the network of contacts. Here, pairwise-approximation methods and full stochastic simulations are used to investigate the utility of contact tracing. A simple relationship is found between the efficiency of contact tracing necessary for eradication and the basic reproductive ratio of the disease. This holds for a wide variety of realistic situations including heterogeneous networks containing core-groups or super-spreaders, and asymptomatic individuals. Clustering (transitivity) within the transmission network is found to destroy the relationship, requiring lower efficiency than predicted.", "qid": 14, "docid": "492xtiqh", "rank": 78, "score": 7.305200099945068}, {"content": "Title: Computational modeling of Human-nCoV protein-protein interaction network Content: COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.", "qid": 14, "docid": "k4f79dr4", "rank": 79, "score": 7.30109977722168}, {"content": "Title: Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin for COVID-19: what is the evidence and what are the risks? Content: The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.", "qid": 14, "docid": "wnb4cltt", "rank": 80, "score": 7.289400100708008}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 14, "docid": "abj9b0x0", "rank": 81, "score": 7.221499919891357}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention. Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 14, "docid": "zbkgabl2", "rank": 82, "score": 7.221498966217041}, {"content": "Title: Strategies adopted and lessons learnt during the severe acute respiratory syndrome crisis in Singapore. Content: In Singapore, the military was actively involved in the containment of the outbreak of severe acute respiratory syndrome (SARS) last year. The outbreak started in February 2003 with three Singapore travellers to Hong Kong. At that time, nothing was known about the aetiological agent of the atypical pneumonia that was termed SARS. Unfortunately one of the travellers was a super-spreader, defined as a person with high efficiency for virus transmission, and was responsible for the expansion of the national outbreak. Not only was the Singapore military involved in contact tracing of personnel and enforcement of home quarantine, military-affiliated research institutes were also involved in providing diagnostic support. This review reconstructs the events that took place during the SARS outbreak, focusing on the special support arising from complementing the military-affiliated laboratory with the public health laboratory. A description of the diagnostic findings is provided in chronological order. The review ends with lessons Singapore learnt from the SARS crisis, stressing the importance of national preparedness for future outbreaks.", "qid": 14, "docid": "yxn8v9q6", "rank": 83, "score": 7.212699890136719}, {"content": "Title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network Content: The entire world has recently witnessed the commencement of coronavirus disease 19 (COVID-19) pandemic. It is caused by a novel coronavirus (n-CoV) generally distinguished as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It has exploited human vulnerabilities to coronavirus outbreak. SARS-CoV-2 promotes fatal chronic respiratory disease followed by multiple organ failure which ultimately puts an end to human life. No proven vaccine for n-CoV is available till date in spite of significant research efforts worldwide. International Committee on Taxonomy of Viruses (ICTV) has reached to a consensus that the virus SARS-CoV-2 is highly genetically similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) outbreak of 2003. It has been reported that SARS-CoV has \u223c89% genetic similarities with n-CoV. With this hypothesis, the current work focuses on the identification of spreader nodes in SARS-CoV protein interaction network. Various network characteristics like edge ratio, neighborhood density and node weight have been explored for defining a new feature spreadability index by virtue of which spreader nodes and edges are identified. The selected top spreader nodes having high spreadability index have been also validated by Susceptible-Infected-Susceptible (SIS) disease model. Initially, the proposed method is applied on a synthetic protein interaction network followed by SARS-CoV-human protein interaction network. Hence, key spreader nodes and edges (ranked edges) are unmasked in SARS-CoV proteins and its connected level 1 and level 2 human proteins. The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art.", "qid": 14, "docid": "5jccb3nh", "rank": 84, "score": 7.114500045776367}, {"content": "Title: Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors Content: The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the \u2018cytokine storm\u2019, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1\u03b2, IL-6 and TNF-\u03b1 secretion via \u2018trained monocytes\u2019, which confers early protection against SARS-CoV2.", "qid": 14, "docid": "6dq6gm27", "rank": 85, "score": 7.07420015335083}, {"content": "Title: The Role of Personality and Linguistic Patterns in Discriminating Between Fake News Spreaders and Fact Checkers Content: Users play a critical role in the creation and propagation of fake news online by consuming and sharing articles with inaccurate information either intentionally or unintentionally. Fake news are written in a way to confuse readers and therefore understanding which articles contain fabricated information is very challenging for non-experts. Given the difficulty of the task, several fact checking websites have been developed to raise awareness about which articles contain fabricated information. As a result of those platforms, several users are interested to share posts that cite evidence with the aim to refute fake news and warn other users. These users are known as fact checkers. However, there are users who tend to share false information, who can be characterised as potential fake news spreaders. In this paper, we propose the CheckerOrSpreader model that can classify a user as a potential fact checker or a potential fake news spreader. Our model is based on a Convolutional Neural Network (CNN) and combines word embeddings with features that represent users\u2019 personality traits and linguistic patterns used in their tweets. Experimental results show that leveraging linguistic patterns and personality traits can improve the performance in differentiating between checkers and spreaders.", "qid": 14, "docid": "b1ph5tuy", "rank": 86, "score": 7.05109977722168}, {"content": "Title: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales. Content: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 14, "docid": "2jttlljm", "rank": 87, "score": 7.035399913787842}, {"content": "Title: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales Content: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 14, "docid": "qg4xl5w8", "rank": 88, "score": 7.035398960113525}, {"content": "Title: The SARS outbreak in a general hospital in Tianjin, China -- the case of super-spreader. Content: Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a high case-fatality rate and devastating socio-economic impact. In this report we summarized the results from an epidemiological investigation of a SARS outbreak in a hospital in Tianjin, between April and May 2003. We collected epidemiological and clinical data on 111 suspect and probable cases of SARS associated with the outbreak. Transmission chain and outbreak clusters were investigated. The outbreak was single sourced and had eight clusters. All SARS cases in the hospital were traced to a single patient who directly infected 33 people. The patients ranged from 16 to 82 years of age (mean age 38.5 years); 38.7% were men. The overall case fatality in the SARS outbreak was 11.7% (13/111). The outbreak lasted around 4 weeks after the index case was identified. SARS is a highly contagious condition associated with substantial case fatality; an outbreak can result from one patient in a relatively short period. However, stringent public health measures seemed to be effective in breaking the disease transmission chain.", "qid": 14, "docid": "j4n2shv4", "rank": 89, "score": 6.948800086975098}, {"content": "Title: Escherichia coli, cattle and the propagation of disease Content: Several early models describing host\u2013pathogen interaction have assumed that each individual host has approximately the same likelihood of becoming infected or of infecting others. More recently, a concept that has been increasingly emphasized in many studies is that for many infectious diseases, transmission is not homogeneous but highly skewed at the level of populations. In what became known as the \u201820/80 rule\u2019, about 20% of the hosts in a population were found to contribute to about 80% of the transmission potential. These heterogeneities have been described for the interaction between many microorganisms and their human or animal hosts. Several epidemiological studies have reported transmission heterogeneities for Escherichia coli by cattle, a phenomenon with far-reaching agricultural, medical and public health implications. Focusing on E. coli as a case study, this paper will describe super-spreading and super-shedding by cattle, review the main factors that shape these transmission heterogeneities and examine the interface with human health. Escherichia coli super-shedding and super-spreading by cattle are shaped by microorganism-specific, cattle-specific and environmental factors. Understanding the factors that shape heterogeneities in E. coli dispersion by cattle and the implications for human health represent key components that are critical for targeted infection control initiatives.", "qid": 14, "docid": "6g1qxz9i", "rank": 90, "score": 6.9095001220703125}, {"content": "Title: Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses; however, appropriate design and conduct of pharmacoepidemiologic studies are needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritise some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to \"real-time epidemiology\" during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting.", "qid": 14, "docid": "dylpa1en", "rank": 91, "score": 6.891900062561035}, {"content": "Title: Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission. Content: BACKGROUND Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.", "qid": 14, "docid": "elho35ot", "rank": 92, "score": 6.872499942779541}, {"content": "Title: Laparoscopic Roux-en-Y gastric bypass in super obese G\u00f6ttingen minipigs. Content: BACKGROUND The specific mechanisms behind weight loss and comorbidity improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still poorly understood. The aim of this study was to establish and evaluate the feasibility of a long-term survival RYGBP model in super obese G\u00f6ttingen minipigs in order to improve the translational potential relative to current animal models. METHODS Eleven G\u00f6ttingen minipigs with diet-induced obesity underwent laparoscopic RYGBP and were followed up to 9 months after surgery. Intra- and post-operative complications, body weight (BW), food intake and necropsy data were recorded. RESULTS Five minipigs survived without complications to the end of the study. Four minipigs developed surgical related complications and were euthanized while two minipigs died due to central venous catheter related complications. BW and food intake is reported for the six minipigs surviving longer than 4.5 months post-surgery. Weight loss and reduced food intake was seen in all minipigs. After 2-3 months of weight loss, weight regain was evident in all but two minipigs which seemed to continue losing weight. Necropsy revealed some variation in the length of the alimentary, biliary and common limb between minipigs. CONCLUSION The use of obese G\u00f6ttingen minipigs as a translational RYGBP model is feasible and has potential for the study of RYGBP-related changes in gut function, type-2 diabetes and appetite regulation. Still, the surgical procedure is technically highly demanding in obese G\u00f6ttingen minipigs and the peri-operative animal care and follow up requires close monitoring.", "qid": 14, "docid": "eg09054j", "rank": 93, "score": 6.8703999519348145}, {"content": "Title: Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission Content: We examined 169 genomes of SARS-CoV-2 and found that they can be classified into two major genotypes, Type I and Type II. Type I can be further divided into Type IA and IB. Our phylogenetic analysis showed that the Type IA resembles the ancestral SARS-CoV-2 most. Type II was likely evolved from Type I and predominant in the infections. Our results suggest that Type II SARS-CoV-2 was the source of the outbreak in the Wuhan Huanan market and it was likely originated from a super-spreader. The outbreak caused by the Type I virus should have occurred somewhere else, because the patients had no direct link to the market. Furthermore, by analyzing three genomic sites that distinguish Type I and Type II strains, we found that synonymous changes at two of the three sites confer higher protein translational efficiencies in Type II strains than in Type I strains, which might explain why Type II strains are predominant, implying that Type II is more contagious (transmissible) than Type I. These findings could be valuable for the current epidemic prevention and control.", "qid": 14, "docid": "a12708qd", "rank": 94, "score": 6.865099906921387}, {"content": "Title: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China. Content: BACKGROUND Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3\u00b723). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0\u00b737). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5\u00b764). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "qid": 14, "docid": "lmw1l7gz", "rank": 95, "score": 6.860300064086914}, {"content": "Title: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China Content: BACKGROUND: Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM: To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS: A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS: A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3\u00b723). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0\u00b737). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5\u00b764). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION: High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "qid": 14, "docid": "x67wh2na", "rank": 96, "score": 6.860299110412598}, {"content": "Title: The epidemiology of the outbreak of severe acute respiratory syndrome (SARS) in Hong Kong--what we do know and what we don't. Content: Severe acute respiratory syndrome (SARS) struck Hong Kong bitterly in the spring of 2003, infecting 1755 persons and claiming nearly 300 lives. The epidemic was introduced by travellers from southern China, where the disease had originated. It started in late February and lasted until early June. Two notable 'super-spreading' events were reported, one inside a teaching hospital and the other in a private housing estate. Other than in the super-spreading events, the infectivity in the community appeared to be low, and there were few, if any, asymptomatic or subclinical infections. Health-care workers were at particular risk and accounted for 22 % of all probable cases. The main modes of transmission were through droplet spread and close/direct contacts, but situations conducive to aerosol generation appeared to be associated with higher risk. Our review suggests that there are still many unknown factors concerning the mode of transmission and environmental risk that need to be clarified.", "qid": 14, "docid": "zqer9w9t", "rank": 97, "score": 6.846199989318848}, {"content": "Title: Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic. Content: The coronavirus disease 2019 (COVID-19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses, however, appropriate design and conduct of pharmacoepidemiologic studies is needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritize some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to 'real-time epidemiology' during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting. This article is protected by copyright. All rights reserved.", "qid": 14, "docid": "olo2ildg", "rank": 98, "score": 6.830599784851074}, {"content": "Title: EveSense: What Can You Sense from Twitter? Content: Social media has become a useful source for detecting real-life events. This paper presents an event detection application EveSense. It detects real-life events and related trending topics from the Twitter stream and allows users to find interesting events that have recently occurred. It uses a novel Dynamic Heartbeat Graph (DHG) approach, which efficiently extracts distinguishing features and performs better than the existing event detection methods. We tested and evaluated the application on three case studies, including a sports event (FA cup Final) and two political events (Super Tuesday and US Election).", "qid": 14, "docid": "h9brighg", "rank": 99, "score": 6.8109002113342285}, {"content": "Title: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore Content: Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.", "qid": 14, "docid": "2t4fsfy9", "rank": 100, "score": 6.786499977111816}]}
{"query": "how long can the coronavirus live outside the body", "hits": [{"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?", "qid": 15, "docid": "959w9sln", "rank": 1, "score": 9.741600036621094}, {"content": "Title: Methusaleh's Zoo: how nature provides us with clues for extending human health span. Content: As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mammals, like the bowhead whale, appear to survive 200 years or more. Another group of species may not be as absolutely long-lived, but they are remarkably long-lived for their body size and metabolic rate. These species include a number of bats, some of which live for at least 40 years in the wild, as well as the naked mole-rat, which is the same size, but lives nearly 10 times as long as the laboratory mouse. Together these exceptionally long-lived organisms have important roles to play in our future understanding of the causal mechanisms and modulation of ageing. Bats and naked mole-rats in particular have already contributed in the following ways: (1) they have contributed to the abandonment of the rate-of-living theory and weakened enthusiasm for the oxidative stress hypothesis of ageing, (2) they have helped evaluate how the tumour-suppressing role of cellular senescence is affected by the evolution of diverse body sizes as well as diverse longevities, (3) they have shed light on the relationship between specific types of DNA repair and ageing and (4) they have yielded insight into new processes, specifically the maintenance of the proteome and hypotheses concerning how evolution shapes ageing. The continuing acceleration of progress in genome sequencing and development of more and more cross-species investigatory techniques will facilitate even more contributions of these species in the near future.", "qid": 15, "docid": "pgsdu0fu", "rank": 2, "score": 9.713800430297852}, {"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US", "qid": 15, "docid": "hgau3922", "rank": 3, "score": 9.63379955291748}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Content: Abstract Background and aim As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. Method We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. Results We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. Conclusion In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.", "qid": 15, "docid": "1de98sxz", "rank": 4, "score": 8.174200057983398}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Content: BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.", "qid": 15, "docid": "1tl71xqw", "rank": 5, "score": 8.174199104309082}, {"content": "Title: HOW LONG WILL MY MOUSE LIVE? MACHINE LEARNING APPROACHES FOR PREDICTION OF MOUSE LIFESPAN Content: Prediction of individual lifespan based upon characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict lifespan in a stock of genetically heterogeneous mice. Lifespan-prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before two years of age, we show that the lifespan quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (\u00b1 0.10%). This result provides a new benchmark for the development of lifespan-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.", "qid": 15, "docid": "486j76e1", "rank": 6, "score": 8.101400375366211}, {"content": "Title: A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam Content: Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs) play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs) including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders\u2019 reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.", "qid": 15, "docid": "b6kx9nnb", "rank": 7, "score": 7.779699802398682}, {"content": "Title: Microbes, Transmission Routes and Survival Outside the Body Content: Microbes like bacteria, virus, parasites and fungi may naturally colonize skin and mucous membranes without any sign of illness, for a longer or shorter period, in all humans, animals, fish, parasites, plants and all other living beings. Some types may be more invasive in human tissue than others. Many microbes are free-living in the environment\u2014in water, soil and air and on equipment\u2014as a part of the normal microbial flora on the Earth. Most of them are not dangerous and live in peaceful symbiosis with other living beings and may also be transferred between living species, from man to animal or man to plants and environment\u2014and vice versa. New and old human pathogenic microbes are increasing all over the world. Some agents, like drug-resistant bacteria and highly pathogenic viruses, are more dangerous than others, and some microbes may cause chronic devastating diseases. Transmission routes depend on the robustness of the microbe in the environment, virulence, infectious dose, anatomical site in the body, etc. Pathogenic microbes are spread by contact, air, water, food, beverages, contaminated equipment and environment and are more seldom vector-borne, by insects or animals. The following chapter is focused on the most frequent pathogenic microbes, their preselected localization in the body, transmission routes and survival in the environment.", "qid": 15, "docid": "zpek8i5e", "rank": 8, "score": 7.778299808502197}, {"content": "Title: Avian coronavirus infectious bronchitis attenuated live vaccines undergo selection of subpopulations and mutations following vaccination Content: In this study, we were interested in determining if high titered egg adapted modified live infectious bronchitis virus (IBV) vaccines contain spike gene related quasispecies that undergo selection in chickens, following vaccination. We sequenced the spike glycoprotein of 12 IBV vaccines (5 different serotypes from 3 different manufacturers) directly from the vaccine vial, then compared that sequence with reisolated viruses from vaccinated and contact-exposed birds over time. We found differences in the S1 sequence within the same vaccine serotype from different manufacturers, differences in S1 sequence between different vaccine serials from the same manufacturer, and intra-vaccine differences or quasispecies. Comparing the sequence data of the reisolated viruses with the original vaccine virus, we were able to identify in vivo selection of viral subpopulations as well as mutations. To our knowledge, this is the first report showing selection of a more fit virus subpopulation as well as mutations associated with replication of modified live IBV vaccine viruses in chickens. This information is important for our understanding of how attenuated virus vaccines, including potential vaccines against the SARS-CoV, can ensure long-term survival of the virus and can lead to changes in pathogenesis and emergence of new viral pathogens. This information is also valuable for the development of safer modified live coronavirus vaccines.", "qid": 15, "docid": "x1wemzgn", "rank": 9, "score": 7.742800235748291}, {"content": "Title: The Science of Wildlife Disease Management Content: In its widest sense disease can be regarded as any impairment of normal functions. However, for the purposes of this book we will mostly restrict our discussion to infectious diseases, the agents of which are often described as parasites or pathogens. For convenience, these organisms are often split into two categories that reflect their broad characteristics, and their relative size. The macroparasites are multi-cellular organisms that live in or on the host, such as helminths and arthropods, while microparasites include viruses, bacteria, fungi and protozoa. The main functional differences between the two relate to their generation times, with microparasites exhibiting relatively higher within-host reproductive rates and shorter generation times than macroparasites. As a result microparasites are frequently associated with acute disease, although they can induce long-lived immunity to re-infection in recovered hosts. Macroparasites by contrast are more likely to produce chronic infections often characterised by short-lived immunity in heavily infected hosts, and re-infection. Macroparasites may also have distinct life stages that can survive outside the host (e.g. eggs or larvae) and sometimes require other host species to complete their life cycle. Two important groups of pathogens fall outside this classification: rogue proteins (prions) implicated in transmissible spongiform encephalopathies (TSEs) and infectious cancers, of which Tasmanian devil facial tumour disease is a well known example. However, in broad respects these are most usefully considered as microparasites, often producing acute clinical signs without host immunity. Disease can affect individual hosts by reducing growth rates or fecundity, increasing metabolic requirements, changing patterns of behaviour and ultimately may cause death. Sub-lethal effects of pathogens may also enhance mortality rates by for example, increasing the susceptibility of the infected host to predation. However, the intimate relationships between hosts and parasites have in many instances evolved over time into subtle and potentially complex interactions, such that infection does not in itself necessarily lead to disease. Many parasites have little detrimental effect on their hosts for most of the time, only causing pathological damage if this delicate balance is upset, for example when the parasites become too numerous or when the immunological capability of the host is impaired. This balance could be influenced by many factors including nutrition, concomitant infections and a variety of physiological stressors.", "qid": 15, "docid": "46hb8fnn", "rank": 10, "score": 7.712600231170654}, {"content": "Title: Infectome: A platform to trace infectious triggers of autoimmunity Content: Abstract The \u201cexposome\u201d is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the \u201cinfectome\u201d, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the \u201cimmunome\u201d and \u201cmicrobiome\u201d projects.", "qid": 15, "docid": "46e6qae9", "rank": 11, "score": 7.49429988861084}, {"content": "Title: Interaction rituals and \u2018social distancing\u2019: New haptic trajectories and touching from a distance in the time of COVID-19 Content: Previous research in the social sciences has shown that haptic interaction rituals are critical for maintaining social relationships. However, during the coronavirus (COVID-19) pandemic, \u2018social distancing\u2019 was encouraged in order to avoid the spread of disease. Drawing on data from self-ethnography as well as publicly available resources, in this study we explore some new, locally negotiated haptic trajectories to accomplish interaction rituals in the time of coronavirus. First, we present self-ethnographic observations of distancing in face-to-face encounters from our everyday lives. Second, utilizing methods of microanalysis of naturally occurring interaction, we investigate video recordings of the embodied negotiation of space and touch among politicians. We analyze three different ways in which politicians negotiate transitional moves in this haptic ritual when one party initiates a handshake: repairing, declining and apologizing. Our analysis shows that politicians adapt their entire bodies in conjunction with talk, gestures and laughter not only to accomplish the greeting but also to remedy the potentially face-threatening situation of not getting the greeting right. This research has implications for better understanding the spontaneous ability of human beings to invent new ways of engaging with each other. Moreover, it adds to our knowledge of how the materiality of human bodies can impact forms of sociality.", "qid": 15, "docid": "k6gg78w1", "rank": 12, "score": 7.3572998046875}, {"content": "Title: Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland. Content: The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 \u00b0C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 \u00b0C. Koala body temperatures as low as 34.2 \u00b0C and as high as 39.0 \u00b0C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 \u00b0C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.", "qid": 15, "docid": "5dzyx6pw", "rank": 13, "score": 7.2459001541137695}, {"content": "Title: Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland Content: The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 \u00b0C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 \u00b0C. Koala body temperatures as low as 34.2 \u00b0C and as high as 39.0 \u00b0C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 \u00b0C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.", "qid": 15, "docid": "j2l61p76", "rank": 14, "score": 7.245899200439453}, {"content": "Title: Humor and sympathy in medical practice Content: Medical professionals seem to interpret their uses of humor very differently from those outside the medical profession. Nurses and physicians argue that humor is necessary for them to do their jobs well. Many (potential) patients are horrified that they could one day be the butt of their physician\u2019s jokes. The purpose of this paper is to encourage the respectful use of humor in clinical prac-tice, so as to support its importance in medical practice, while simultaneously protecting against its potential abuse. I begin by examining two extremes of supporting or chastising the use of medical humor. I look at these views through the lenses of popular theories of humor to help explain their theoretical bases. In this second section, I explain the emotional aspect of humor as an embodied and embedded transformation of the world. This clarifies the role that humor plays in our daily lives, as well as why the ethical or unethical nature of its use is dependent on context. Third, I address the potential problems in the relationship between humor and clinical sympathy, and how this further affects the relationship between medical professionals and their patients. I conclude by arguing that humor can conflict with clinical sympathy, but this need not be the case. If medical professionals actively engage with clinical sympathy and focus on using humor in a way that is respectful towards their patients, then humor can continue to be a positive force in their lives while still providing the best care for their patients.", "qid": 15, "docid": "21ldudka", "rank": 15, "score": 7.1402997970581055}, {"content": "Title: Reflecting upon vulnerable and dependent bodies during the COVID\u201019 crisis Content: This paper is a short narrative on how feminism helped me find a balance in my life and how this balance has been disrupted with the Covid\u201019 crisis. I reflect on how this crisis is showing our vulnerabilities as human beings. This crisis reflects how our bodies depend on each other, moving away from the dominant patriarchal ontology that perceives bodies as being independent (Butler, 2016). I reflect on how this crisis is letting the most vulnerable in situations of survival because the infrastructures (Butler, 2016) that support our bodies are not functioning. At the same time, this crisis is providing visibility to certain occupations that are dominated by issues of race, class and gender. These occupations are being at least temporarily rehabilitated to their central position in society. We are living a time where we could show, through our teaching, possible resistance to the neoliberal ontology that captured humanity.", "qid": 15, "docid": "4aa20cut", "rank": 16, "score": 7.118500232696533}, {"content": "Title: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19). Content: Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "qid": 15, "docid": "4n2xmx2w", "rank": 17, "score": 7.105100154876709}, {"content": "Title: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19) Content: Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "qid": 15, "docid": "s6oi477q", "rank": 18, "score": 7.105099201202393}, {"content": "Title: Estimate the incubation period of coronavirus 2019 (COVID-19) Content: Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.", "qid": 15, "docid": "vkgnwxzc", "rank": 19, "score": 7.099999904632568}, {"content": "Title: Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China Content: A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of husband and wife without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of S genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37x10-3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.", "qid": 15, "docid": "m9k6upe4", "rank": 20, "score": 6.965400218963623}, {"content": "Title: The Short-run and Long-run Effects of Covid-19 on Energy and the Environment Content: Summary/Abstract We explore how the short-run effects of Covid-19 in reducing CO2 and local air pollutant emissions can easily be outweighed by the long-run effects of a slowing of clean energy innovation. Focusing on the United States, we show that in the short run, Covid-19 has reduced consumption for jet fuel and gasoline dramatically, by 50% and 30% respectively, while electricity demand has declined by less than 10%. CO2 emissions have declined by 15%, while local air pollutants have also declined, saving about 200 lives per month. However, there could be a deep impact on long-run innovation in clean energy, leading to an additional 2,500 MMT CO2 and 40 deaths per month on average to 2035. Even pushing back renewable electricity generation investments by one year would outweigh the emission reductions and avoided deaths from March-June 2020. The policy response will determine how Covid-19 ultimately influences the future path of emissions.", "qid": 15, "docid": "56p8ou3l", "rank": 21, "score": 6.905399799346924}, {"content": "Title: A systematic review of non-pharmacological interventions to improve nighttime sleep among residents of long-term care settings. Content: BACKGROUND Disturbances in sleep and circadian rhythms are common among residents of long-term care facilities. In this systematic review, we aim to identify and evaluate the literature documenting the outcomes associated with non-pharmacological interventions to improve nighttime sleep among long-term care residents. METHODS The Preferred Reporting Items for Systematic Reviews guided searches of five databases (MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library) for articles reporting results of experimental or quasi-experimental studies conducted in long-term care settings (nursing homes, assisted-living facilities, or group homes) in which nighttime sleep was subjectively or objectively measured as a primary outcome. We categorized each intervention by its intended use and how it was administered. RESULTS Of the 54 included studies evaluating the effects of 25 different non-pharmacological interventions, more than half employed a randomized controlled trial design (n = 30); the others used a pre-post design with (n = 11) or without (n = 13) a comparison group. The majority of randomized controlled trials were at low risk for most types of bias, and most other studies met the standard quality criteria. The interventions were categorized as environmental interventions (n = 14), complementary health practices (n = 12), social/physical stimulation (n = 11), clinical care practices (n = 3), or mind-body practices (n = 3). Although there was no clear pattern of positive findings, three interventions had the most promising results: increased daytime light exposure, nighttime use of melatonin, and acupressure. CONCLUSIONS Non-pharmacological interventions have the potential to improve sleep for residents of long-term care facilities. Further research is needed to better standardize such interventions and provide clear implementation guidelines using cost-effective practices.", "qid": 15, "docid": "6k8lat9y", "rank": 22, "score": 6.899799823760986}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 15, "docid": "9sbyha2v", "rank": 23, "score": 6.895500183105469}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: Abstract The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 15, "docid": "jxzvyfwx", "rank": 24, "score": 6.895499229431152}, {"content": "Title: Higher Education Institutions in Ukraine during the Coronavirus, or COVID-19, Outbreak: New Challenges vs New Opportunities Content: In a matter of weeks the coronavirus (COVID-19) pandemic has changed students' way of learning across the globe These changes let us envisage how education can modify for better or otherwise for worse over the long term COVID-19 2019/2020 has encouraged Higher Education Institutions in Ukraine to make innovative decisions in a relatively short period of time To provide distance education in Ukrainian universities during the quarantine there have been introduced offline and online courses through various web servers, platforms, resources, and social media: Moodle, Zoom, Skype, Viber, Telegram, Messenger, Google-class etc The summarized results of the questionnaire among Ukrainian students provided an opportunity to identify difficulties and benefits of introduced distance-learning The sources to provide the information for this work included regulations issued by public authorities in Ukraine (Head of State, executive and legislative bodies) as well as directives to administrations of Ukrainian higher education institutions", "qid": 15, "docid": "5er3tg6g", "rank": 25, "score": 6.881199836730957}, {"content": "Title: Mutagenic analysis of the coronavirus intergenic consensus sequence. Content: Previously, a system in which an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells was established. In the present study, a DI cDNA containing one UCUAAAC consensus sequence in the middle of the 0.3-kb-long intergenic region located between genes 6 and 7 was constructed. From this DI cDNA clone, 21 mutant DI RNAs were constructed so that each of the seven consensus sequence nucleotides was changed individually to the three alternative bases. These mutants were used to define how changes in the integrity of MHV transcription consensus sequence UCUAAAC affected mRNA transcription. Except for two mutants with the sequences UGUAAAC and UCGAAAC, all of the mutants supported efficient subgenomic DI RNA transcription. This indicated that MHV transcription regulation was sufficiently flexible to recognize altered consensus sequences. Next, these and other mutants were used to examine the leader-body fusion site on the subgenomic DI RNAs. Sequence analysis demonstrated that all subgenomic DI RNAs analyzed contained two pentanucleotide sequences; the first sequence seemed to be contributed by the leader, and the leader-body fusion most likely took place at either the first or the second nucleotide of the second sequence. This observation was not consistent with the proposed coronavirus transcription model (S. C. Baker and M. M. C. Lai, EMBO J. 9:4173-4179, 1990) which states that nucleotide mismatch can be corrected by RNA polymerase proofreading activity.", "qid": 15, "docid": "39po6wpq", "rank": 26, "score": 6.871200084686279}, {"content": "Title: Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases Content: Exosomes are 40\u2013100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may impact the fields of nephrology and renal physiology in the next few years.", "qid": 15, "docid": "4p68aym1", "rank": 27, "score": 6.869699954986572}, {"content": "Title: COVID-19 length of hospital stay: a systematic review and data synthesis Content: Background The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care. Methods We performed a systematic review to gather data on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach we provide distributions for general hospital and ICU LoS from studies in China and elsewhere, for use by the community. Results We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies - four each within and outside China - with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR: 10-19) days for China, compared with 5 (IQR: 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date. Conclusion Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.", "qid": 15, "docid": "rso45gkx", "rank": 28, "score": 6.861999988555908}, {"content": "Title: Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM Content: Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.", "qid": 15, "docid": "cr22vp8b", "rank": 29, "score": 6.853600025177002}, {"content": "Title: Risk factors for pneumonia and influenza hospitalizations in long-term care facility residents: a retrospective cohort study Content: BACKGROUND: Older adults who reside in long-term care facilities (LTCFs) are at particularly high risk for infection, morbidity and mortality from pneumonia and influenza (P&I) compared to individuals of younger age and those living outside institutional settings. The risk factors for P&I hospitalizations that are specific to LTCFs remain poorly understood. Our objective was to evaluate the incidence of P&I hospitalization and associated person- and facility-level factors among post-acute (short-stay) and long-term (long-stay) care residents residing in LTCFs from 2013 to 2015. METHODS: In this retrospective cohort study, we used Medicare administrative claims linked to Minimum Data Set and LTCF-level data to identify short-stay (< 100 days, index = admission date) and long-stay (100+ days, index = day 100) residents who were followed from the index date until the first of hospitalization, LTCF discharge, Medicare disenrollment, or death. We measured incidence rates (IRs) for P&I hospitalization per 100,000 person-days, and estimated associations with baseline demographics, geriatric syndromes, clinical characteristics, and medication use using Cox regression models. RESULTS: We analyzed data from 1,118,054 short-stay and 593,443 long-stay residents. The crude 30-day IRs (95% CI) of hospitalizations with P&I in the principal position were 26.0 (25.4, 26.6) and 34.5 (33.6, 35.4) among short- and long-stay residents, respectively. The variables associated with P&I varied between short and long-stay residents, and common risk factors included: advanced age (85+ years), admission from an acute hospital, select cardiovascular and respiratory conditions, impaired functional status, and receipt of antibiotics or Beers criteria medications. Facility staffing and care quality measures were important risk factors among long-stay residents but not in short-stay residents. CONCLUSIONS: Short-stay residents had lower crude 30- and 90-day incidence rates of P&I hospitalizations than long-stay LTCF residents. Differences in risk factors for P&I between short- and long-stay populations suggest the importance of considering distinct profiles of post-acute and long-term care residents in infection prevention and control strategies in LTCFs. These findings can help clinicians target interventions to subgroups of LTCF residents at highest P&I risk.", "qid": 15, "docid": "5ig4r9bi", "rank": 30, "score": 6.808899879455566}, {"content": "Title: Being HIV positive and staying on antiretroviral therapy in Africa: A qualitative systematic review and theoretical model. Content: BACKGROUND Adherence to antiretroviral therapy (ART) and long-term uninterrupted engagement in HIV care is difficult for HIV-positive people, and randomized trials of specific techniques to promote adherence often show small or negligible effects. Understanding what influences decision-making in HIV-positive people in Africa may help researchers and policy makers in the development of broader, more effective interventions and policies. METHODS We used thematic synthesis and a grounded theory approach to generate a detailed narrative and theoretical model reflecting life with HIV in Africa, and how this influences ART adherence and engagement decisions. We included qualitative primary studies that explored perspectives, perceptions and experiences of HIV-positive people, caregivers and healthcare service providers. We searched databases from 1 January 2013 to 9 December 2016, screened all studies, and selected those for inclusion using purposeful sampling methods. Included studies were coded with Atlas.ti, and we assessed methodological quality across five domains. RESULTS We included 59 studies from Africa in the synthesis. Nine themes emerged which we grouped under three main headings. First, people who are HIV-positive live in a complicated world where they must navigate the challenges presented by poverty, competing priorities, unpredictable life events, social identity, gender norms, stigma, and medical pluralism-these influences can make initiating and maintaining ART difficult. Second, the health system is generally seen as punishing and uninviting and this can drive HIV-positive people out of care. Third, long-term engagement and adherence requires adaptation and incorporation of ART into daily life, a process which is facilitated by: inherent self-efficacy, social responsibilities, previous HIV-related illnesses and emotional, practical or financial support. These factors together can lead to a \"tipping point\", a point in time when patients choose to either engage or disengage from care. HIV-positive people may cycle in and out of these care states in response to fluctuations in influences over time. CONCLUSION This analysis provides a practical theory, arising from thematic synthesis of research, to help understand the dynamics of adherence to ART and engagement in HIV care. This can contribute to the design of service delivery approaches, and informed thinking and action on the part of policy makers, providers, and society: to understand what it is to be HIV-positive in Africa and how attitudes and the health service need to shift to help those with HIV lead 'normal' lives.", "qid": 15, "docid": "wdik9jcz", "rank": 31, "score": 6.753699779510498}, {"content": "Title: Does form meet function in the coronavirus replicative organelle? Content: If we use the analogy of a virus as a living entity, then the replicative organelle is the part of the body where its metabolic and reproductive activities are concentrated. Recent studies have illuminated the intricately complex replicative organelles of coronaviruses, a group that includes the largest known RNA virus genomes. This review takes a virus-centric look at the coronavirus replication transcription complex organelle in the context of the wider world of positive sense RNA viruses, examining how the mechanisms of protein expression and function act to produce the factories that power the viral replication cycle.", "qid": 15, "docid": "6s01qplg", "rank": 32, "score": 6.732900142669678}, {"content": "Title: Astrovirology, Astrobiology, Artificial Intelligence: Extra-Solar System Investigations Content: This chapter attempts to encompass and tackle a large problem in Astrovirology and Astrobiology. There is a huge anthropomorphic prejudice that although life is unlikely, the just-right Goldilocks terrestrial conditions mean that the just-right balance of minerals and basic small molecules inevitably result in life as we know it throughout our solar system, galaxy, and the rest of the universe. Moreover, when such conditions on planets such as ours may not be quite right for the origin of life, it is popularly opined that asteroids and comets magically produce life or at the very least, the important, if not crucial components of terrestrial life so that life then blooms, when their fragments cruise the solar system, stars, and galaxies, and plummet onto appropriately bedecked planets and moons. It is no longer extraordinary to detect extraterrestrial solar systems. Moreover, since extra-solar system space exploration has commenced, this provides the problem of detecting life with enhanced achievability. Small organisms, which replicate outside of a living cell or host, would not be catalogued as viruses. How about viruses that cohabit with life? On the Earth, viruses are a major, if underestimated, condition of life \u2013 will that be the case elsewhere? Detection of extra-solar system viruses, if they exist, requires finding life, since viruses necessitate life to replicate. (It should be noted, though, that viruses could be detected through various types of portable ultra-microscopes, including Electron Microscopes (EM) (scanning and transmission) as well as Atomic Force Microscopes (AFM).) However, extra-solar system detection of life does not oblige that viruses exist ubiquitously. Viruses are important potential components of biospheres because of their multiple interactions and influence on evolution, although viruses are small and obligatory parasitic. In addition, nanotechnology \u2013 living or replicating nano-synthetic machine organisms might also be present out there, and require consideration as well. An imposing caveat is that, if found, could some extraterrestrial viruses and synthetic nanotechnological microorganisms infect humans? Possibly, intelligence and cognition may at times be contemporaneous with life. Concomitantly, life and viruses that may be detected, could well be impacted upon by intelligences existing on such exoplanets (and vice versa). Coming to an understanding of the plurality of extraterrestrial intelligence is an optimal objective, in order to avoid causing harm on exoplanets, as well as avoiding conflict and possible human devastation. This is especially the case if we encounter greatly advanced galactic-level civilizations, compared to terrestrial civilizations. Their machine and bionic technologies on the Dyson engineering civilization scale may be prominently superior to ours; their biological expertise may be similarly critically radical. For example, they may use viruses for purposes for which we are barely aware, and which could be utterly deadly for humans. A series of steps is being taken in space exploration. Scientists hypothesize and claim that types of life may be near the Earth, in the solar system, and outside the solar system, similar to ours in the sense that only such conditions, Goldilocks conditions, are key sine qua non requirements, based on our terrestrial chemistry and biochemistry. If detected within the solar system, will life or its remnants resemble terrestrial life? Outside the solar system a similar chauvinism exists, although the likelihood for life, in any event, remains probably low, according to more cautious approaches to the problem. The study of our solar system includes planets, asteroids, comets, and other planetesimals that have been in overall contiguity during several billion years; anthropomorphisms claims life consequently has been developing along terrestrial-type mechanisms. However, a non-anthropomorphic view would surmise, probably not, especially for extra-solar system locales. The prime warning and admonition in all these deliberations is the contamination and damage, which current and past practice and procedures has caused and continues, due to insufficient biocontainment concepts and technology to date. Advances in the development of robotics, artificial intelligence (AI), and high capacity ultrafast quantum computers (QC) greatly enhance the sophisticated control and logical development of extra-solar system studies. Consequently, future long-range manned space exploration seems unwarranted. Clearly, reduced dangers to human health and safety, will result from the use of intelligent machine-based investigations and besides, with increased cost-effectiveness. Space exploration comes at great cost to humanity as a whole and utilizes global resources. Consequently, appropriate organizational measures and planning/cooperation need to be in place. Moreover, the bottom line is that despite all the slogans and claims, there have been next to no financial benefits to our planet as a whole. Such financial and heedless difficulties need to be addressed, the sooner the better. In addition, prior to exposure to exoplanetary life, deep understanding of the problems of infectious diseases and immune dysfunction risks are needed. In addition, global efforts should avoid serendipity and stochasticity as this work should be directed with long-term organization, commitment, scientific, and technological methodology. This chapter briefly reviews such questions assuming a new paradigm for oversight of extrasolar system viral investigations including intelligence and life. Finances are included as an essential adjunct.", "qid": 15, "docid": "aq82tqay", "rank": 33, "score": 6.7144999504089355}, {"content": "Title: Infection Control in Dental Practice During the COVID-19 Pandemic Content: COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.", "qid": 15, "docid": "1d4gf7kr", "rank": 34, "score": 6.694300174713135}, {"content": "Title: Infection Control in Dental Practice During the COVID-19 Pandemic. Content: COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.", "qid": 15, "docid": "i62url4t", "rank": 35, "score": 6.694299221038818}, {"content": "Title: Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase. Content: BACKGROUND Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. METHODS The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. RESULTS Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p < 0.01] and follicular [dysmenorrhoeics vs. controls mean (SD): 60 (18) mm vs. 40 (14) mm, p < 0.01] phases of the menstrual cycle. CONCLUSIONS These data show that compared with controls, women who experience severe recurrent dysmenorrhoea have deep-tissue hyperalgesia to ischaemic pain in muscles outside of the referred area of menstrual pain both during the painful menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation.", "qid": 15, "docid": "9gvgvk8m", "rank": 36, "score": 6.681600093841553}, {"content": "Title: \u2018The economy\u2019 as if people mattered: revisiting critiques of economic growth in a time of crisis Content: Coronavirus (COVID-19) policy shut down the world economy with a range of government actions unprecedented outside of wartime. In this paper, economic systems dominated by a capital accumulating growth imperative are shown to have had their structural weaknesses exposed, revealing numerous problems including unstable supply chains, unjust social provisioning of essentials, profiteering, precarious employment, inequities and pollution. Such phenomena must be understood in the context of long standing critiques relating to the limits of economic systems, their consumerist values and divorce from biophysical reality. Critical reflection on the Coronavirus pandemic is combined with a review of how economists have defended economic growth as sustainable, Green and inclusive regardless of systemic limits and multiple crises\u2013climate emergency, economic crash and pandemic. Instead of rebuilding the old flawed political economy again, what the world needs now is a more robust, just, ethical and equitable social-ecological economy.", "qid": 15, "docid": "1fk6zcqi", "rank": 37, "score": 6.671000003814697}, {"content": "Title: Absencing/presencing risk: Rethinking proximity and the experience of living with major technological hazards Content: Abstract There is now a substantial body of sociocultural research that has investigated the ways in which specific communities living in physical proximity with a variety of polluting or hazardous technological installations experience and respond to their exposure to the associated risk. Much of this research has sought to understand the apparent acceptance or acquiescence displayed by local populations towards established hazards of the kind that are typically resisted when the subject of siting proposals. However, recent theoretical contributions, produced largely outside the field of risk research, have problematised the objective distinction between proximity and distance. In this paper we explore the potential of some of these ideas for furthering our understanding of the relationship between place and the constitution of risk subjectivities. To do this we re-examine a number of existing sociocultural studies that are predicated on a localised approach and conceptualise the relationship of physically proximate sources of risk to everyday experience in terms of practices of \u2018presencing\u2019 and \u2018absencing\u2019. We conclude with some thoughts on the methodological and substantive implications of this reworking of proximity for future research into risk subjectivities.", "qid": 15, "docid": "dkncpt8g", "rank": 38, "score": 6.622499942779541}, {"content": "Title: Preventing and responding to depression, self-harm, and suicide in older people living in long term care settings: a systematic review. Content: OBJECTIVE The well documented demographic shift to an aging population means that more people will in future be in need of long term residential care. Previous research has reported an increased risk of mental health issues and suicidal ideation among older people living in residential care settings. However, there is little information on the actual prevalence of depression, self-harm, and suicidal behavior in this population, how it is measured and how care homes respond to these issues. METHOD This systematic review of international literature addressed three research questions relating to; the prevalence of mental health problems in this population; how they are identified and; how care homes try to prevent or respond to mental health issues. RESULTS Findings showed higher reported rates of depression and suicidal behavior in care home residents compared to matched age groups in the community, variation in the use of standardised measures across studies and, interventions almost exclusively focused on increasing staff knowledge about mental health but with an absence of involvement of older people themselves in these programmes. CONCLUSION We discuss the implications of these findings in the context of addressing mental health difficulties experienced by older people in residential care and future research in this area.", "qid": 15, "docid": "ycry015n", "rank": 39, "score": 6.620999813079834}, {"content": "Title: Sleep quality, mental health and circadian rhythms during COVID lockdown: Results from the SleepQuest Study Content: Behavioural responses to COVID19 lockdown will define the long-term impact of psychological stressors on sleep and brain health. Here we tease apart factors that help protect against sleep disturbance. We capitalise on the unique restrictions during COVID19 to understand how time of day of daylight exposure and outside exercise interact with chronotype and sleep quality. 3474 people from the UK (median age 62, range 18 to 91) completed our online 'SleepQuest' Study between 29th April and 13th May 2020 - a set of validated questionnaires probing sleep quality, depression, anxiety and attitudes to sleep alongside bespoke questions on the effect of COVID19 lockdown on sleep, time spent outside and exercising and self-help sleep measures. Significantly more people (n=1252) reported worsened than improved sleep (n=562) during lockdown (p<0.0001). Factors significantly associated with worsened sleep included low mood (p<0.001), anxiety (p<0.001) and suspected, proven or at risk of COVID19 symptoms (all p<0.03). Sleep improvement was related to the increased length of time spent outside (P<0.01). Older people's sleep quality was less affected than younger people by COVID19 lockdown (p<0.001). Better sleep quality was associated with going outside and exercising earlier, rather than later, in the day. However, the benefit of being outside early is driven by improved sleep in 'owl' (p=0.0002) and not 'lark' (p=0.27) chronotype, whereas, the benefit of early exercise (inside or outside) did not depend on chronotype. Defining the interaction between chronotype, mental health and behaviour will be critical for targeted lifestyle adaptations to protect brain health through current and future crises.", "qid": 15, "docid": "laph0zjc", "rank": 40, "score": 6.594200134277344}, {"content": "Title: Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women Content: BACKGROUND: The beginning of 2020 was characterized by the COVID-19 pandemic. The world governments have adopted restrictive measures to reduce the spread of infection. These measures could affect the sexual function and quality of life of women living with their partner. AIM: The aim is to assess the impact of the social distancing measures caused by the COVID-19 pandemic on sexual function and quality of life of noninfected reproductive-age women, living with their sexual partner. METHODS: Observational analysis on sexually active women, living with their partner, and without COVID-19 infection was performed. The population previously answered FSFI, FSDS, and SF-36 questionnaires. 4 weeks after the introduction of the restrictive measures, these women were invited to complete the same questionnaires by e-mail for an evaluation during the COVID-19 outbreak. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of the women's sex function change during the social restriction period, by analyzing the FSFI and FSDS questionnaires. The secondary endpoint was the evaluation of the impact on the quality of life calculated by the SF-36 questionnaire. RESULTS: 89 patients were considered. The median age was 39 (28\u201350) years. Mean sexual intercourses/month decreased from 6.3 \u00b1 1.9 to 2.3 \u00b1 1.8, mean difference: \u22123.9 \u00b1 1.2. FSFI decreased significantly (29.2 \u00b1 4.2 vs 19.2 \u00b1 3.3, mean difference: \u22129.7 \u00b1 2.6) and FSDS increased significantly (9.3 \u00b1 5.5 vs 20.1 \u00b1 5.2, mean difference: 10.8 \u00b1 3.4). The SF-36 showed a significant change from 82.2 \u00b1 10.2 to 64.2 \u00b1 11.8 4 weeks after the introduction of the restrictive measures; mean difference: \u221217.8 \u00b1 6.7. The univariable analysis identified working outside the home, university educational level, and parity \u22651 as predictive factors of lower FSFI. In multivariable analysis, working outside the home and combination of working outside the home + university educational level + parity \u22651 were the independent factors of a lower FSFI. CLINICAL IMPLICATION: The negative impact of the COVID-19 epidemic period on sexual function and quality of life in women shows how acute stress might affect the psychological state. Thus, psychological or sexual support could be useful. STRENGTHS AND LIMITATIONS: To our knowledge, this study is the first that analyzes the change in sexual activity in women during the COVID-19 outbreak period. The limitations were the low number of the analyzed participants, psychological tests were not included, and no data were collected on masturbation, self-heroism, solitary, and nonpenetrative sex. CONCLUSION: The COVID-19 epidemic and the restrictive social distancing measures have negatively influenced the sexual function and quality of life in not-infected reproductive-age women who live with their sexual partners. Schiavi MC, Spina V, Zullo MA, et al. Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women. J Sex Med 2020;XX:XXX\u2013XXX.", "qid": 15, "docid": "d3o07fw7", "rank": 41, "score": 6.593599796295166}, {"content": "Title: Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women Content: BACKGROUND: The beginning of 2020 was characterized by the COVID-19 pandemic. The world governments have adopted restrictive measures to reduce the spread of infection. These measures could affect the sexual function and quality of life of women living with their partner. AIM: The aim is to assess the impact of the social distancing measures caused by the COVID-19 pandemic on sexual function and quality of life of noninfected reproductive-age women, living with their sexual partner. METHODS: Observational analysis on sexually active women, living with their partner, and without COVID-19 infection was performed. The population previously answered FSFI, FSDS, and SF-36 questionnaires. 4 weeks after the introduction of the restrictive measures, these women were invited to complete the same questionnaires by e-mail for an evaluation during the COVID-19 outbreak. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of the women's sex function change during the social restriction period, by analyzing the FSFI and FSDS questionnaires. The secondary endpoint was the evaluation of the impact on the quality of life calculated by the SF-36 questionnaire. RESULTS: 89 patients were considered. The median age was 39 (28-50) years. Mean sexual intercourses/month decreased from 6.3 \u00b1 1.9 to 2.3 \u00b1 1.8, mean difference: -3.9 \u00b1 1.2. FSFI decreased significantly (29.2 \u00b1 4.2 vs 19.2 \u00b1 3.3, mean difference: -9.7 \u00b1 2.6) and FSDS increased significantly (9.3 \u00b1 5.5 vs 20.1 \u00b1 5.2, mean difference: 10.8 \u00b1 3.4). The SF-36 showed a significant change from 82.2 \u00b1 10.2 to 64.2 \u00b1 11.8 4 weeks after the introduction of the restrictive measures; mean difference: -17.8 \u00b1 6.7. The univariable analysis identified working outside the home, university educational level, and parity &#8805;1 as predictive factors of lower FSFI. In multivariable analysis, working outside the home and combination of working outside the home + university educational level + parity &#8805;1 were the independent factors of a lower FSFI. CLINICAL IMPLICATION: The negative impact of the COVID-19 epidemic period on sexual function and quality of life in women shows how acute stress might affect the psychological state. Thus, psychological or sexual support could be useful. STRENGTHS AND LIMITATIONS: To our knowledge, this study is the first that analyzes the change in sexual activity in women during the COVID-19 outbreak period. The limitations were the low number of the analyzed participants, psychological tests were not included, and no data were collected on masturbation, self-heroism, solitary, and nonpenetrative sex. CONCLUSION: The COVID-19 epidemic and the restrictive social distancing measures have negatively influenced the sexual function and quality of life in not-infected reproductive-age women who live with their sexual partners. Schiavi MC, Spina V, Zullo MA, et al. Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women. J Sex Med 2020;XX:XXX-XXX.", "qid": 15, "docid": "td05l9ct", "rank": 42, "score": 6.59359884262085}, {"content": "Title: Self-Direction of Home and Community-Based Services in the Time of COVID-19. Content: During the COVID-19 pandemic, nursing homes and assisted living facilities have accounted for over 20% of all infections, adult day care and other congregate sites have closed, and traditional home care agencies are facing staff shortages. In this environment, self-direction of home and community-based services, where the participant can hire their own staff and manage a budget that can be used for a broad range of goods and services including home modifications and assistive devices, is seen as a promising intervention. Using self-direction participants can minimize the number of people who enter their homes and pay close family and friends who were already providing many hours of informal care, and now may be unemployed. The Center for Medicare and Medicaid Services is encouraging this approach. This commentary presents information on how states have responded using the new CMS Toolkit by expanding who can be a paid caregiver, increasing budgets and broadening the kinds of items that can be purchased with budgets to include items like personal protective equipment and supports for telehealth. This Commentary concludes with policy and research questions regarding how the delivery of long-term services and supports (LTSS) may change as the world returns to\"normal\".", "qid": 15, "docid": "1bakthrw", "rank": 43, "score": 6.58620023727417}, {"content": "Title: Self-Direction of Home and Community-Based Services in the Time of COVID-19 Content: During the COVID-19 pandemic, nursing homes and assisted living facilities have accounted for over 20% of all infections, adult day care and other congregate sites have closed, and traditional home care agencies are facing staff shortages. In this environment, self-direction of home and community-based services, where the participant can hire their own staff and manage a budget that can be used for a broad range of goods and services including home modifications and assistive devices, is seen as a promising intervention. Using self-direction participants can minimize the number of people who enter their homes and pay close family and friends who were already providing many hours of informal care, and now may be unemployed. The Center for Medicare and Medicaid Services is encouraging this approach. This commentary presents information on how states have responded using the new CMS Toolkit by expanding who can be a paid caregiver, increasing budgets and broadening the kinds of items that can be purchased with budgets to include items like personal protective equipment and supports for telehealth. This Commentary concludes with policy and research questions regarding how the delivery of long-term services and supports (LTSS) may change as the world returns to\"normal\".", "qid": 15, "docid": "1c360pvm", "rank": 44, "score": 6.5861992835998535}, {"content": "Title: Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids Content: Abstract The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.", "qid": 15, "docid": "75u57fw1", "rank": 45, "score": 6.582200050354004}, {"content": "Title: Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids Content: The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.", "qid": 15, "docid": "up5jpq45", "rank": 46, "score": 6.5821990966796875}, {"content": "Title: Effectiveness of Social Networks for Studying Biological Agents and Identifying Cancer Biomarkers Content: Social networks form phenomena that exist and evolve; they are dynamic. These phenomena have been realized and studied by the anthropology and sociology research communities since 1930. However, the recent rapid development in information technology and the internet has increased the interest in social networks and as a model they have been adapted to more applications and domains. Though researchers first studied social networks of humans, for our study described in this chapter we argue that genes and proteins act collaboratively and exist in communities analogous to humans, animals, insects, etc. They complement each other and collectively achieve specific tasks where some would have major roles appearing upfront and others may play minor background roles. However, molecules turn into aggressive actors when their internal structure is augmented; consequently, they may deviate from their target, change camp, and disturb other molecules leading to disaster. Such mutations may be uncontrolled and unintentionally occur inside a body, or they may be intentional and controlled by humans to serve one of two purposes, treatment or bioterrorism. In other words, mutation in the molecules (genes) can lead to a change in behavior. This may lead to good or bad effect, e.g., recovery from illness or diseases that may severely affect the body causing disability or death. Once mutated outside the body, molecules may turn into harmful biological weapons of mass destruction. The latter process does not require sophisticated equipment and hence is extremely dangerous with the uprising global terrorism activities. Bioterrorism is therefore a serious concern for humanity. One could say that mutated biological agents outside the body once misused could be way more dangerous than mutated molecules within the body. In this chapter, we will elaborate on bioterrorism and its consequences; we will also propose a model to study social networks of genes within the body leading to the identification of disease biomarkers.", "qid": 15, "docid": "nx6gofu7", "rank": 47, "score": 6.544899940490723}, {"content": "Title: Bats and Emerging Infections: An Ecological and Virological Puzzle Content: More than 200 viruses have been detected in bats. Some unique bat characteristics can explain the roles played in the maintenance and transmission of viruses: long phylogenetic history can have originated coevolution processes, great number of species are adapted to live in different environments, big mobility, long lifespan and gregarious behaviour of many species. To analyse zoonoses long longitudinal studies are needed with a multidisciplinary approximation to obtain the following eco-epidemiological data: colony size, number of bats per species, population structure, behaviour of each species, degree of contact between bats, social structure, remaining time of bats in the colony, colony type, foraging area, turnover rate of individuals, shelter temperature, relationship with other colonies and co-infection processes. These data allows assessing the epidemiological risk and which preventive measures are necessary to take. The structure and functionality of ecosystems are changing worldwide at an unprecedented rate and can modify the interactions between humans and infected bats. There are more or less local factors that can affect the emergence and spread of diseases (environmental alterations, changes in land use, human population growth, changes in human socioeconomic behavior or social structure, people mobility increase, trade increase, forest fires, extreme weather events, wars, breakdown in public health infrastructure, etc.). Twenty-three percent of all bat species in the world are decreasing. How does the regression of bat species affect the dynamic of viruses? The dichotomy between health risk and bat preservation is compatible with a preventive task based on more information and training.", "qid": 15, "docid": "amzc5yrd", "rank": 48, "score": 6.536499977111816}, {"content": "Title: COVID-19 and Cities: from Urban Health strategies to the pandemic challenge. A Decalogue of Public Health opportunities. Content: BACKGROUND AND AIM OF THE WORK The ongoing pandemic of COVID-19, which nowadays has exceeded 2.5 million notified infections in the world and about 200,000 deaths, is a strong reminder that urbanization has changed the way that people and communities live, work, and interact, and it's necessary to make resilient the systems and local capacities to prevent the spread of infectious diseases. How we can re-design the concept of Public Health in relation to the built environment and the contemporary cities? METHODS According to the previous statements and scenario, aim of this paper is to integrate the Urban Health strategic objectives, focusing the possible responses, both immediate and medium-long term, to the current environmental, social, and economic aspects of the \"period\" of physical distancing. Results. Immediate Actions are 01. program the flexibility of city schedules; 02. plan a smart and sustainable mobility network; 03. define a neighborhood services' plan; 04. develop a digitization of the urban context, promoting the smart communities; 05. re-think the accessibility to the places of culture and tourism. Medium-long term Actions are 06. design the indoor flexibility of domestic living spaces; 07. re-think building typologies, fostering the presence of semi-private or collective spaces; 08. renovate the basic care services' network; 09. integrate the existing environmental emergency plans, with those related to the health emergencies; 10. improve stakeholders' awareness of the factors affecting Public Health in the cities. CONCLUSIONS The Decalogue of Public Health opportunities may provide a useful basis for Designers (Architects and Urban Planners), Policy Makers, Public Health experts and Local Health Agencies, in promoting actions and policies aimed to transform our cities in healthier and Salutogenic living environments. (www.actabiomedica.it).", "qid": 15, "docid": "4q8h1yxo", "rank": 49, "score": 6.532100200653076}, {"content": "Title: COVID-19 and Cities: from Urban Health strategies to the pandemic challenge. A Decalogue of Public Health opportunities Content: BACKGROUND AND AIM OF THE WORK: The ongoing pandemic of COVID-19, which nowadays has exceeded 2.5 million notified infections in the world and about 200,000 deaths, is a strong reminder that urbanization has changed the way that people and communities live, work, and interact, and it's necessary to make resilient the systems and local capacities to prevent the spread of infectious diseases. How we can re-design the concept of Public Health in relation to the built environment and the contemporary cities? METHODS: According to the previous statements and scenario, aim of this paper is to integrate the Urban Health strategic objectives, focusing the possible responses, both immediate and medium-long term, to the current environmental, social, and economic aspects of the \"period\" of physical distancing. Results. Immediate Actions are 01. program the flexibility of city schedules; 02. plan a smart and sustainable mobility network; 03. define a neighborhood services' plan; 04. develop a digitization of the urban context, promoting the smart communities; 05. re-think the accessibility to the places of culture and tourism. Medium-long term Actions are 06. design the indoor flexibility of domestic living spaces; 07. re-think building typologies, fostering the presence of semi-private or collective spaces; 08. renovate the basic care services' network; 09. integrate the existing environmental emergency plans, with those related to the health emergencies; 10. improve stakeholders' awareness of the factors affecting Public Health in the cities. CONCLUSIONS: The Decalogue of Public Health opportunities may provide a useful basis for Designers (Architects and Urban Planners), Policy Makers, Public Health experts and Local Health Agencies, in promoting actions and policies aimed to transform our cities in healthier and Salutogenic living environments. (www.actabiomedica.it).", "qid": 15, "docid": "ff1nqh22", "rank": 50, "score": 6.53209924697876}, {"content": "Title: Modelling the spread of COVID-19 with new fractal-fractional operators: Can the lockdown save mankind before vaccination? Content: Countries around the world are implementing lock-down measures in a bid to flatten the curve of the new deadly COVID-19 disease. Our paper does not claim to have found the cure for COVID-19, neither does it claim that the suggested model have taken into account all the complexities around the spread of the disease. Nonetheless, the fundamental question asked in this paper is to know if within the conditions taken into account in this suggested model, the integral lock-down is effective in saving human lives. To answer this question, a mathematical model was suggested taking into account the possibility of transmission of COVID-19 from dead bodies to humans and the effect of lock-down. Three cases were considered. The first case suggested that there is transmission from dead to the living (medical staffs as they perform postmortem procedures on corpses, and direct contacts with during burial ceremonies). This case has no equilibrium points except for disease free equilibrium, a clear indication that care must be taken when dealing with corpses due to corona-19. In the second case we removed the transmission rate from dead bodies. This case showed an equilibrium point, although the number of deaths, carriers and infected grew exponentially up to a certain stability level. In the last case, we incorporated a lock-down and social distancing effect, using the next generation matrix. We could achieve a zero reproduction number, with number of deaths, infected and carriers decaying very rapidly. This is a clear indication that if lock-down recommendations are observed the threat of COVID-19 can be reduced to zero in few months.While our mathematical model agrees with the effectiveness of the lock-down, it is important to mention damaging effects of inadequate testing. The long waiting period of few days before confirmation of status, can only lead to more infections. The asymptomatic tested person could be positive and spread the infection, or could contact the virus in days after testing and will spread the disease further, after being given a false result. Testing kit that with immediate results are needed for more efficient measures. We used Italy\u2019s Data to guide the construction of the mathematical model. To include non-locality into mathematical formulas, differential and integral operators were suggested. Properties and numerical approximations were presented in details. Finally, the suggested differential and integral operators were applied to the model.", "qid": 15, "docid": "rmbavm9i", "rank": 51, "score": 6.522500038146973}, {"content": "Title: Modelling the spread of COVID-19 with new fractal-fractional operators: Can the lockdown save mankind before vaccination? Content: Countries around the world are implementing lock-down measures in a bid to flatten the curve of the new deadly COVID-19 disease. Our paper does not claim to have found the cure for COVID-19, neither does it claim that the suggested model have taken into account all the complexities around the spread of the disease. Nonetheless, the fundamental question asked in this paper is to know if within the conditions taken into account in this suggested model, the integral lock-down is effective in saving human lives. To answer this question, a mathematical model was suggested taking into account the possibility of transmission of COVID-19 from dead bodies to humans and the effect of lock-down. Three cases were considered. The first case suggested that there is transmission from dead to the living (medical staffs as they perform postmortem procedures on corpses, and direct contacts with during burial ceremonies). This case has no equilibrium points except for disease free equilibrium, a clear indication that care must be taken when dealing with corpses due to corona-19. In the second case we removed the transmission rate from dead bodies. This case showed an equilibrium point, although the number of deaths, carriers and infected grew exponentially up to a certain stability level. In the last case, we incorporated a lock-down and social distancing effect, using the next generation matrix. We could achieve a zero reproduction number, with number of deaths, infected and carriers decaying very rapidly. This is a clear indication that if lock-down recommendations are observed the threat of COVID-19 can be reduced to zero in few months.While our mathematical model agrees with the effectiveness of the lock-down, it is important to mention damaging effects of inadequate testing. The long waiting period of few days before confirmation of status, can only lead to more infections. The asymptomatic tested person could be positive and spread the infection, or could contact the virus in days after testing and will spread the disease further, after being given a false result. Testing kit that with immediate results are needed for more efficient measures. We used Italy's Data to guide the construction of the mathematical model. To include non-locality into mathematical formulas, differential and integral operators were suggested. Properties and numerical approximations were presented in details. Finally, the suggested differential and integral operators were applied to the model.", "qid": 15, "docid": "xds1t447", "rank": 52, "score": 6.522499084472656}, {"content": "Title: Risk assessment of novel coronavirus COVID-19 outbreaks outside China Content: We developed a computational tool to assess the risk of novel coronavirus outbreaks outside China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia and Europe, and we investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.", "qid": 15, "docid": "ecu579el", "rank": 53, "score": 6.47790002822876}, {"content": "Title: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China Content: We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas;(ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination;and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ) We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc Countries in the middle should consider a combination of such policies Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing", "qid": 15, "docid": "fpexj3s5", "rank": 54, "score": 6.477899074554443}, {"content": "Title: Boosted Ensemble Learning for Anomaly Detection in 5G RAN Content: The emerging 5G networks promises more throughput, faster, and more reliable services, but as the network complexity and dynamics increases, it becomes more difficult to troubleshoot the systems. Vendors are spending a lot of time and effort on early anomaly detection in their development cycle and majority of the time is spent on manually analyzing system logs. While main research in anomaly detection uses performance metrics, anomaly detection using functional behaviour is still lacking in depth analysis. In this paper we show how a boosted ensemble of Long Short Term Memory classifiers can detect anomalies in the 5G Radio Access Network system logs. Acquiring system logs from a live 5G network is difficult due to confidentiality issues, live network disturbance, and problems to repeat scenarios. Therefore, we perform our evaluation on logs from a 5G test bed that simulate realistic traffic in a city. Our ensemble learns the functional behaviour of an application by training on logs from normal execution time. It can then detect deviations from normal behaviour and also be retrained on false positive cases found during validation. Anomaly detection in RAN shows that our ensemble called BoostLog, outperforms a single LSTM classifier and further testing on HDFS logs confirms that BoostLog also can be used in other domains. Instead of using domain experts to manually analyse system logs, BoostLog can be used by less experienced trouble shooters to automatically detect anomalies faster and more reliable.", "qid": 15, "docid": "lq8z4syu", "rank": 55, "score": 6.459400177001953}, {"content": "Title: Watch the coronavirus\u2019 rampage through the body Content: Science\u2019s COVID-19 reporting is supported by the Pulitzer Center SARS-CoV-2, the virus that causes COVID-19, can severely damage lungs, but in serious cases it doesn\u2019t stop there\u2014clinicians have observed bodywide damage because of the coronavirus As researchers begin to better understand the pathology of the disease, new treatments can be deployed to help save lives Clinicians see a range of impacts from COVID-19\u2014from pulmonary embolisms to kidney damage", "qid": 15, "docid": "3eysv9sl", "rank": 56, "score": 6.456200122833252}, {"content": "Title: COVID-19 pandemic in the African continent: forecasts of cumulative cases, new infections, and mortality Content: Background: Africa is the last major region to capitulate to the SARS-CoV-2 (COVID-19) pandemic. The first confirmed COVID-19 case in the region was reported on February 14, but what lies ahead in terms of the course and magnitude of infection remains speculative. To the best of our knowledge, no study, using a robust methodology, provides the immediate and long-term trajectory of COVID-19 for the entire region or accounts for its local context. This paper is the first systematic attempt to provide estimates on how many people would contract the virus and how many would die in the coming few months across Africa. Methods: The forecasts on caseloads and incidences are from a co-variate-based instrumental variable regression model. Fatality rates from Italy and China were further applied to generate mortality estimates after adjustments were made for differences in age-structure, health service quality, and living standards between each of the African countries and those of the reference population. We cover all countries that reported a confirmed case as of March 31, 2020. Results: By the end of June, 16,283,085 people will contract COVID-19 (95% CI 718,403 to 98, 358, 799). With a cumulative caseload of 5,413,4517 (95% CI 1,332,953 to 8,489,940) and 906,625 (95% CI 173, 821 to 4,742,917) Northern and Eastern Africa will respectively be the most and least affected sub-regions in the continent. Cumulative COVID-19 cases on June 30, 2020 are expected to reach 2,912, 864 (95% CI 465,028 to 18,286,358) in Southern Africa, 2,787, 913 (95% CI 517, 489 to 15,056,314) in Western Africa, and 1,185,742 (95% CI 229, 111 to 6,138,692) in Central Africa. New infections (incidence) for the month of April are expected to be the highest in Djibouti, 32.8 per 1000 (95% CI 6.25 to 171.77), while Morocco 1045 (95% CI 167 to 6,547) will register the highest number of deaths. Conclusion: Our study shows that countries that are least urbanized and have a low level of socio-economic development, hence least connected to the outside world, are likely to register lower and slower transmissions, at least at the early stage of the epidemic. However, the same set of enabling factors that worked for their benefit are likely to go against them in implementing interventions that have lessened the impact of the disease elsewhere.", "qid": 15, "docid": "atee6lis", "rank": 57, "score": 6.451200008392334}, {"content": "Title: Cities and population health Content: A majority of the world's population will live in urban areas by 2007 and cities are exerting growing influence on the health of both urban and non-urban residents. Although there long has been substantial interest in the associations between city living and health, relatively little work has tried to understand how and why cities affect population health. This reflects both the number and complexity of determinants and of the absence of a unified framework that integrates the multiple factors that influence the health of urban populations. This paper presents a conceptual framework for studying how urban living affects population health. The framework rests on the assumption that urban populations are defined by size, density, diversity, and complexity, and that health in urban populations is a function of living conditions that are in turn shaped by municipal determinants and global and national trends. The framework builds on previous urban health research and incorporates multiple determinants at different levels. It is intended to serve as a model to guide public health research and intervention.", "qid": 15, "docid": "myjbk7ye", "rank": 58, "score": 6.448299884796143}, {"content": "Title: The Challenges of COVID-19 for People Living With Diabetes: Considerations for Digital Health Content: The coronavirus disease (COVID-19) is a global pandemic that significantly impacts people living with diabetes. Diabetes-related factors of glycemic control, medication pharmacodynamics, and insulin access can impact the severity of a COVID-19 infection. In this commentary, we explore how digital health can support the diabetes community through the pandemic. For those living with diabetes, digital health presents the opportunity to access care with greater convenience while not having to expose themselves to infection in an in-person clinic. Digital diabetes apps can increase agency in self-care and produce clinically significant improvement in glycemic control through facilitating the capture of diabetes device data. However, the ability to share these data back to the clinic to inform virtual care and enhance diabetes coaching and guidance remains a challenge. In the end, it requires an unnecessarily high level of technical sophistication on the clinic's part and on those living with diabetes to routinely use their diabetes device data in clinic visits, virtual or otherwise. As the world comes together to fight the COVID-19 pandemic, close collaboration among the global diabetes community is critical to understand and manage the sustained impact of the pandemic on people living with diabetes.", "qid": 15, "docid": "56tdmfp3", "rank": 59, "score": 6.433800220489502}, {"content": "Title: The Challenges of COVID-19 for People Living With Diabetes: Considerations for Digital Health Content: The coronavirus disease (COVID-19) is a global pandemic that significantly impacts people living with diabetes. Diabetes-related factors of glycemic control, medication pharmacodynamics, and insulin access can impact the severity of a COVID-19 infection. In this commentary, we explore how digital health can support the diabetes community through the pandemic. For those living with diabetes, digital health presents the opportunity to access care with greater convenience while not having to expose themselves to infection in an in-person clinic. Digital diabetes apps can increase agency in self-care and produce clinically significant improvement in glycemic control through facilitating the capture of diabetes device data. However, the ability to share these data back to the clinic to inform virtual care and enhance diabetes coaching and guidance remains a challenge. In the end, it requires an unnecessarily high level of technical sophistication on the clinic\u2019s part and on those living with diabetes to routinely use their diabetes device data in clinic visits, virtual or otherwise. As the world comes together to fight the COVID-19 pandemic, close collaboration among the global diabetes community is critical to understand and manage the sustained impact of the pandemic on people living with diabetes.", "qid": 15, "docid": "8lhkiw9p", "rank": 60, "score": 6.4337992668151855}, {"content": "Title: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China Content: We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number [Formula: see text]). We found that in countries with low connectivity to China but with relatively high [Formula: see text] , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low [Formula: see text] benefit the most from policies that further reduce [Formula: see text]. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.", "qid": 15, "docid": "axljtddn", "rank": 61, "score": 6.433199882507324}, {"content": "Title: Dis-ease Surveillance: How Might Surveillance Studies Address COVID-19? Content: We are currently in the midst of a global pandemic with the spread of Coronavirus Disease 2019 (COVID-19) While we do not know how this situation will unfold or resolve, we do have insight into how it fits within existing patterns and relations, particularly those pertaining to sociocultural constructions of (in)security, vulnerability, and risk We can see evidence of surveillance dynamics at play with how bodies and pathogens are being measured, tracked, predicted, and regulated We can grasp how threat is being racialized, how and why institutions are flailing, and how social media might be fueling social divisions There is, in other words, a lot that our scholarly community could add to the conversation In this rapid-response editorial, we provide an introduction to the framing devices of disease surveillance and discuss how a surveillance studies orientation could help us think critically about the present crisis and its possible aftermath", "qid": 15, "docid": "x8qsmlw5", "rank": 62, "score": 6.396299839019775}, {"content": "Title: Social Distancing as a Network Population Game in a Socially Connected World Content: While social living is considered to be an indispensable part of human life in today's ever-connected world, social distancing has recently received much public attention on its importance since the outbreak of the coronavirus pandemic. In fact, social distancing has long been practiced in nature among solitary species, and been taken by human as an effective way of stopping or slowing down the spread of infectious diseases. Here we consider a social distancing problem for how a population, when in a world with a network of social sites, such as schools, restaurants, shopping centers, residential areas, etc., decides to visit or stay at some sites while avoiding or closing down others so that the social contacts across the network can be minimized. We model this problem as a network population game, where every individual tries to find some network sites to visit or stay so that he/she can minimize all his/her contacts. In the end, an optimal strategy can be found for every one, when the resulting distribution of the population over the network reaches an equilibrium. We show that a large class of equilibrium strategies can be obtained by selecting a set of network sites that forms a so-called maximal r-regular subnetwork. The latter includes many well studied network types, such as the maximal independent set (r=0), the maximal strong matching (r=1), the maximal set of independent cycles (r=2), etc. They are easy to identify or construct, and can be completely disconnected (with r = 0) for the most strict isolation, or allow certain degree of connectivities (with r>0) for more flexible distancing. We derive the equilibrium conditions of these strategies, and analyze their rigidity and flexibility on different types of r-regular subnetworks. We provide an overview on algorithms that can be used for computing maximal r-regular subnetworks and their associated distancing strategies.", "qid": 15, "docid": "qev9sryo", "rank": 63, "score": 6.382800102233887}, {"content": "Title: Comfortably Numb in the Midst of the Corona Crisis Content: The coronavirus has taken the West by surprise It has called into question basic assumptions about globalisation, how our society is organised, how safe we actually are and to what extent we control the world around us The virus arrived when we were without the proper conceptual framework to deal with a new type of virus, and we could not have imagined how much of a social challenge it would represent The novelty of the situation has made most of us feel strangely confused, numb and calm, and in many cases has left us not knowing what to do with ourselves This satirical review seeks to put some distance and detachment between us and the situation and give us an outside perspective of what the corona crisis can teach us, both at the individual and social levels Before the situation becomes the ?new normal?, we should take the time to extract some lessons from this mess", "qid": 15, "docid": "dpupzthk", "rank": 64, "score": 6.370999813079834}, {"content": "Title: \u2018All the single ladies\u2019 as the ideal academic in times of Covid-19? Content: Much of what has hitherto been written about women?s lived experiences of the coronavirus pandemic takes their status as mothers and the spouses of men for granted Skewed care demands on women researchers working from home may translate into individual career disadvantage and cumulative, large-scale gender inequalities in the future, which is undeniably a serious issue However, the narrative that single, childfree women must currently, by contrast, be unconcernedly enjoying a surge of productivity needs to be nuanced Therefore, with this paper, I autoethnographically discuss how living alone in the context of the Covid-19 pandemic provides its own set of circumstances and is hardly problem-free, which affects how one can deal with issues of academic productivity and work-life balance Also, I take issue with the premise that our productivity is the golden standard against which we and our worth should be measured while we are living through a global crisis", "qid": 15, "docid": "94so2gfe", "rank": 65, "score": 6.366600036621094}, {"content": "Title: Outcomes after long-term mechanical ventilation of cancer patients Content: BACKGROUND: The probability of weaning and of long-term survival of chronically mechanically ventilated cancer patients is unknown, with incomplete information available to guide therapeutic decisions. We sought to determine the probability of weaning and overall survival of cancer patients requiring long-term mechanical ventilation in a specialized weaning unit. METHODS: A single-institution retrospective review of patients requiring mechanical ventilation outside of a critical care setting from 2008 to 2012 and from January 1 to December 31, 2018, was performed. Demographic and clinical data were recorded, including cancer specifics, comorbidities, treatments, and outcomes. Overall survival was determined using the Kaplan-Meier approach. Time to weaning was analyzed using the cumulative incidence function, with death considered a competing risk. Prognostic factors were evaluated for use in prospective evaluations of weaning protocols. RESULTS: Between 2008 and 2012, 122 patients required mechanical ventilation outside of a critical care setting with weaning as a goal of care. The cumulative incidence of weaning after discharge from the intensive care unit was 42% at 21 days, 49% at 30 days, 58% at 60 days, 61% at 90 days, and 61% at 120 days. The median survival was 0.16 years (95% CI, 0.12 to 0.33) for those not weaned and 1.05 years (95% CI, 0.60 to 1.34) for those weaned. Overall survival at 1 year and 2 years was 52 and 32% among those weaned and 16 and 9% among those not weaned. During 2018, 36 patients at our institution required mechanical ventilation outside of a critical care setting, with weaning as a goal of care. Overall, with a median follow-up of 140 days (range, 0\u2013425 days; average, 141 days), 25% of patients requiring long-term mechanical ventilation (9 of 36) are alive. CONCLUSIONS: Cancer patients can be weaned from long-term mechanical ventilation, even after prolonged periods of support. Implementation of a resource-intensive weaning program did not improve rates of successful weaning. No clear time on mechanical ventilation could be identified beyond which weaning was unprecedented. Short-term overall survival for these patients is poor.", "qid": 15, "docid": "u5ecibta", "rank": 66, "score": 6.3649001121521}, {"content": "Title: Station\u00e4re Psychosomatik in Zeiten des Coronavirus./ [Inpatient psychosomatics in times of the coronavirus] Content: The current coronavirus 2019 (COVID-19) pandemic presents psychosomatic clinics with new challenges. In order that psychotherapists in private practice can also obtain a picture for their patients, this article deals with the core aspects of hygiene. There are three fundamental patterns of care and provisions by the institutions that can be differentiated: rededication, stepwise evacuation and stand-by for rededication and continuation of the service under medical epidemic conditions. The following topics are the relevant contents: need for consultation in the matter of anxiety for coronavirus and interpersonal mental and psychosomatic problems due to the necessary social distancing, care especially in precarious living situations, altered communication structures (telephone, video consultation) and care of those occupied with the topic of \"coronavirus disease 2019\" (COVID-19). All patients undergo a clinical and virologic diagnostic process before admittance and receive psychosomatic psychotherapeutic inpatient care, possibly beginning under quarantine conditions. Furthermore, appropriate general hygiene regulations are explained. Finally, what the patients are told is illustrated using a simple schematic aid: distance (minimum 2 m), rubbing (wash hands with soap often and for at least 20 s), avoidance (pass by in a friendly manner), alternative communication, forsaking (shopping is not always necessary), wiping (regularly wipeing of all surfaces by the cleaning personnel as well as tablet and mobile telephone by the patients themselves) and outside activity as much as possible, alone or sitting together (with safety distance). The psychosomatic services were appropriately converted.", "qid": 15, "docid": "yjmada6s", "rank": 67, "score": 6.357500076293945}, {"content": "Title: Immunological fortification at our barrier organs: Protecting us as we age. Content: Our barrier surfaces are fundamental in protecting us from the outside world and segregating key biological processes. The immunological fortifications found at these sites therefore possess many distinct qualities, which are discussed in Immunology's series of reviews on Barrier Immunity. Together these reviews showcase novel biological processes identified through the use of state-of-the-art technologies, and specifically highlight how these change throughout our lives.", "qid": 15, "docid": "gm9j0b58", "rank": 68, "score": 6.3541998863220215}, {"content": "Title: Chapter One Parasites of seabirds: A survey of effects and ecological implications Content: Abstract Parasites are ubiquitous in the environment, and can cause negative effects in their host species. Importantly, seabirds can be long-lived and cross multiple continents within a single annual cycle, thus their exposure to parasites may be greater than other taxa. With changing climatic conditions expected to influence parasite distribution and abundance, understanding current level of infection, transmission pathways and population-level impacts are integral aspects for predicting ecosystem changes, and how climate change will affect seabird species. In particular, a range of micro- and macro-parasites can affect seabird species, including ticks, mites, helminths, viruses and bacteria in gulls, terns, skimmers, skuas, auks and selected phalaropes (Charadriiformes), tropicbirds (Phaethontiformes), penguins (Sphenisciformes), tubenoses (Procellariiformes), cormorants, frigatebirds, boobies, gannets (Suliformes), and pelicans (Pelecaniformes) and marine seaducks and loons (Anseriformes and Gaviiformes). We found that the seabird orders of Charadriiformes and Procellariiformes were most represented in the parasite-seabird literature. While negative effects were reported in seabirds associated with all the parasite groups, most effects have been studied in adults with less information known about how parasites may affect chicks and fledglings. We found studies most often reported on negative effects in seabird hosts during the breeding season, although this is also the time when most seabird research occurs. Many studies report that external factors such as condition of the host, pollution, and environmental conditions can influence the effects of parasites, thus cumulative effects likely play a large role in how parasites influence seabirds at both the individual and population level. With an increased understanding of parasite-host dynamics it is clear that major environmental changes, often those associated with human activities, can directly or indirectly affect the distribution, abundance, or virulence of parasites and pathogens.", "qid": 15, "docid": "re9c3e0b", "rank": 69, "score": 6.338500022888184}, {"content": "Title: News at a glance. Content: In science news around the world, the World Health Organization cautions governments against introducing \"immunity passports that declare people immune to COVID-19 after they test positive for antibodies to the new coronavirus;the group notes a lack of evidence that people with such antibodies are protected from a second infection The U S National Institutes of Health ends a long-standing grant for research on how viruses spread from bats and other wildlife to humans after conservative politicians criticize the project's ties to a lab in Wuhan, China, that they blame, without evidence, for being the source of the COVID-19 virus The U S Food and Drug Administration advises physicians not to prescribe the antimalarial drugs chloroquine and hydroxychloroquine for COVID-19 patients outside of hospitals or clinical trials, citing safety concerns The U S Supreme Court gives hydrologic science top billing in a closely watched ruling affirming that the federal Clean Water Act covers groundwater pollution Donald Kennedy, former editor-in-chief of Science, dies at the age of 88 from COVID-19", "qid": 15, "docid": "nam9jp3c", "rank": 70, "score": 6.333700180053711}, {"content": "Title: Urban food sovereignty: urgent need for agroecology and systems thinking in a post-COVID-19 future Content: The current COVID-19 pandemic has brought attention to challenges associated with our dominant industrial food system in the U.S. The general public now has more appreciation for farm workers and meatpacking employees, as well as those in grocery stores and in food transportation who are suddenly recognized as essential frontline workers. It apparently takes a crisis for us to focus clearly on the fragility of this system and the lives of people on whom we depend. In this commentary we discuss the definition of food sovereignty, how it manifests in urban areas, and how the COVID-19 pandemic can trigger viable responses to increase urban food sovereignty. While recognizing and appreciating the value of trade and comparative advantages of some regions with long seasons to produce food for others, there is strong reason to explore the potentials of local and urban production and governance to avoid serious impacts of unexpected interruptions in the world order.", "qid": 15, "docid": "bsymc7w2", "rank": 71, "score": 6.306000232696533}, {"content": "Title: Station\u00e4re Psychosomatik in Zeiten des Coronavirus Content: The current coronavirus 2019 (COVID-19) pandemic presents psychosomatic clinics with new challenges. In order that psychotherapists in private practice can also obtain a picture for their patients, this article deals with the core aspects of hygiene. There are three fundamental patterns of care and provisions by the institutions that can be differentiated: rededication, stepwise evacuation and stand-by for rededication and continuation of the service under medical epidemic conditions. The following topics are the relevant contents: need for consultation in the matter of anxiety for coronavirus and interpersonal mental and psychosomatic problems due to the necessary social distancing, care especially in precarious living situations, altered communication structures (telephone, video consultation) and care of those occupied with the topic of \u201ccoronavirus disease 2019\u201d (COVID-19). All patients undergo a clinical and virologic diagnostic process before admittance and receive psychosomatic psychotherapeutic inpatient care, possibly beginning under quarantine conditions. Furthermore, appropriate general hygiene regulations are explained. Finally, what the patients are told is illustrated using a simple schematic aid: distance (minimum 2 m), rubbing (wash hands with soap often and for at least 20 s), avoidance (pass by in a friendly manner), alternative communication, forsaking (shopping is not always necessary), wiping (regularly wipeing of all surfaces by the cleaning personnel as well as tablet and mobile telephone by the patients themselves) and outside activity as much as possible, alone or sitting together (with safety distance). The psychosomatic services were appropriately converted.", "qid": 15, "docid": "42wlbcbm", "rank": 72, "score": 6.303400039672852}, {"content": "Title: The ethics of sharing preliminary research findings during public health emergencies: a case study from the 2009 influenza pandemic. Content: During the 2009 A(H1N1) influenza pandemic, a suite of studies conducted in Canada showed an unexpected finding, that patients with medically attended laboratory-confirmed pandemic influenza were more likely to have received seasonal influenza vaccination than test-negative control patients. Different bodies, including scientific journals and government scientific advisory committees, reviewed the evidence simultaneously to determine its scientific validity and implications. Decision-making was complicated when the findings made their way into the media. The normal trajectory of non-urgent research includes peer-review publication after which decision-makers can process the information taking into account other evidence and logistic considerations. In the situation that arose, however, the congruence of an unexpected finding and the simultaneous review of the evidence both within and outside the traditional peer-review sphere raised several interesting issues about how to deal with emerging evidence during a public health emergency. These events are used in this article to aid discussion of the complex interrelationship between researchers, public health decision-makers and scientific journals, the trade-offs between sharing information early and maintaining the peer-review quality assurance process, and to emphasise the need for critical reflection on the practical and ethical norms that govern the way in which research is evaluated, published and communicated in public health emergencies.", "qid": 15, "docid": "xg868v5n", "rank": 73, "score": 6.297100067138672}, {"content": "Title: Functional traits explain amphibian distribution in the Brazilian Atlantic Forest Content: AIM: Species distributions are one of the most important ways to understand how communities interact through macroecological relationships. The functional abilities of a species, such as its plasticity in various environments, can determine its distribution, species richness and beta diversity patterns. In this study, we evaluate how functional traits influence the distribution of amphibians, and hypothesize which functional traits explain the current pattern of amphibian species composition. LOCATION: Atlantic Forest, Brazil. TAXON: Amphibia (Anura and Gymnophiona) METHODS: Using potential distributions of Brazilian amphibians from Atlantic Forest based on their functional traits, we analysed the influence of biotic and abiotic factors on species richness, endemism (with permutation multivariate analysis) and beta diversity components (i.e. total, turnover and nestedness dissimilarities). RESULTS: Environmental variables explained 59.5% of species richness, whereas functional traits explained 15.8% of species distribution (geographical species range) for Anuran and 88.8% for Gymnophiona. Body size had the strongest correlation with species distribution. Results showed that species with medium to large body size, and species that are adapted to living in open areas tended to disperse from west to east direction. Current forest changes directly affected beta diversity patterns (i.e. most species adapted to novel environments increase their ranges). Beta diversity partitioning between humid and dry forests showed decreased nestedness and increased turnover by increasing altitude in the south\u2010eastern region of the Atlantic Forest. MAIN CONCLUSIONS: Our study shows that functional traits directly influence the ability of the species to disperse. With the alterations of the natural environment, species more apt to these alterations have dispersed or increased their distribution, which consequently changes community structure. As a result, there are nested species distribution patterns and homogenization of amphibian species composition throughout the Brazilian Atlantic Forest.", "qid": 15, "docid": "c980uv3z", "rank": 74, "score": 6.290800094604492}, {"content": "Title: From the \u201cMadding Crowd\u201d to mass gatherings-religion, sport, culture and public health Content: Abstract Human behavior has long engaged in collective behavior assembling in crowds. The Christian pilgrimage to the Holy Land has been recorded since the 4th century, while the Hajj, Islam's great pilgrimage, has existed for fourteen centuries, of which a body of literature devoted to the travelogues of the Hajj has been recorded for over ten centuries. Football is a sport played worldwide by more than 1.5 million teams and in 300,000 clubs. Most however play outside of the officially organized sphere: more than 4 percent of the global population plays football, including 270 million amateur players. Assembling for specific events is a uniquely human behavior, though the formal study of crowds did not begin until the mid-Twentieth Century. Today Mass Gathering Medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. All of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. Certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching, uplifting and overwhelming, just as much as they may be at times dangerous and high risk. This review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on Hajj, among the largest of all mass gatherings today. We will find there are some powerful similarities as well as stark differences. Each bequeaths a legacy which can inform the other and, as we make our observations, we join with you and the legions of other investigators who continue to remain fascinated and enthralled by mass gatherings which are among the most beloved and beholden events of modern humanity.", "qid": 15, "docid": "xjbz9fw9", "rank": 75, "score": 6.280900001525879}, {"content": "Title: Ultrastructure of human nasal epithelium during an episode of coronavirus infection Content: The nasal epithelium from a young girl was examined by electron microscopy and found to be infected by coronavirus. Virions are seen within and outside the ciliated cells, but not outside or within the goblet cells or other cells of the nasal mucosa. Some virions are located near the microvilli, others in pockets in the apical cell membrane. The cytoplasm contains many small vesicles with a single virion, large apical vesicles containing hundreds of virions, and lysosome-like cytosomes with a moderate number of virions. Some viruslike particles devoid of an electron-dense interior are seen both in the cytosomes and extracellularly. Virus budding was observed in the Golgi apparatus but nowhere else in the cell. The ciliated cells seem not to be destroyed by the viruses, although in many cases the cilia are withdrawn into the cell body. The loss of cilia is likely to cause rhinorrhoea.", "qid": 15, "docid": "4od8qt36", "rank": 76, "score": 6.267199993133545}, {"content": "Title: The Anxiety of Being Asian American: Hate Crimes and Negative Biases During the COVID-19 Pandemic Content: In this essay, we review how the COVID-19 (coronavirus) pandemic that began in the United States in early 2020 has elevated the risks of Asian Americans to hate crimes and Asian American businesses to vandalism. During the COVID-19 pandemic, the incidents of negative bias and microaggressions against Asian Americans have also increased. COVID-19 is directly linked to China, not just in terms of the origins of the disease, but also in the coverage of it. Because Asian Americans have historically been viewed as perpetually foreign no matter how long they have lived in the United States, we posit that it has been relatively easy for people to treat Chinese or Asian Americans as the physical embodiment of foreignness and disease. We examine the historical antecedents that link Asian Americans to infectious diseases. Finally, we contemplate the possibility that these experiences will lead to a reinvigoration of a panethnic Asian American identity and social movement.", "qid": 15, "docid": "uiezqa4p", "rank": 77, "score": 6.257400035858154}, {"content": "Title: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China Content: Cases of coronavirus disease 2019 (COVID-19) emigrating from Wuhan escalated the risk of spreading the disease in other cities. This report focused on outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Contact investigation was conducted on each patient who was admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from 22 January to 23 February 2020. Cases were confirmed by the polymerase chain reaction test. Demographic, clinical, and outcomes were collected and analyzed. Of the 104 patients, 48 (46.15%) were cases who immigrated from Wuhan; 93 (89.42%) had a definite contact history with infection. Family clusters were the major body of patients. Transmission along the chain of three \"generations\" was observed. Five asymptomatic infected cases were found and two of them infected their relatives. Mean age was 43 (range, 8-84) years, and 49 (47.12%) were male. The median incubation period was 6 (range, 1-32) days, which of 8 patients ranged from 18 to 32 days, 96 (92.31%) were discharged, and 1 (0.96%) died. The average hospital stay was 10 (range, 8-14) days. Family but not community transmission became the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown worked well. Asymptomatic transmission demonstrated here warned us that it may lead to the widespread of COVID-19. A 14-day quarantine may need to be prolonged.", "qid": 15, "docid": "65kw5eof", "rank": 78, "score": 6.244200229644775}, {"content": "Title: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside\u2010Wuhan patients, China Content: OBJECTIVE: Cases with coronavirus disease 2019 (COVID\u201019) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside\u2010Wuhan patients to assess the transmission and clinical characteristics of this illness. METHODS: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 23, 2020. Patients were confirmed by PCR test. Demographic, clinical and outcomes were collected and analyzed. RESULTS: Of the 104 patients, 48 (46.15%) were imported cases who were immigrated from Wuhan; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 \u201cgenerations\u201d was observed. Five asymptomatic infections were found and 2 of them infected their relatives. Mean age was 43 (rang, 8\u201084) years and 49 (47.12%) were male. The median incubation period was 6 (rang, 1\u201032) days, of 8 patients ranged from 18 to 32 days, 96 (92.31%) discharged and 1 (0.96%) died. Average hospital stay was 10 (rang, 8\u201014) days. CONCLUSIONS: Family but not community transmission occupied the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown wok well. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID\u201019. A 14\u2010day quarantine may need to be prolonged. This article is protected by copyright. All rights reserved.", "qid": 15, "docid": "wfnlp15o", "rank": 79, "score": 6.244199275970459}, {"content": "Title: Autophagy in viral replication and pathogenesis Content: Autophagy is a catabolic process that is important for the removal of damaged organelles and long-lived proteins for the maintenance of cellular homeostasis. It can also serve as innate immunity to remove intracellular microbial pathogens. A growing list of viruses has been shown to affect this cellular pathway. Some viruses suppress this pathway for their survival, while others enhance or exploit this pathway to benefit their replication. The effect of viruses on autophagy may also sensitize cells to death or enhance cell survival and play a critical role in viral pathogenesis. In this article, we review the relationships between different viruses and autophagy and discuss how these relationships may affect viruses and their host cells.", "qid": 15, "docid": "m1wm72do", "rank": 80, "score": 6.203700065612793}, {"content": "Title: Mitigating the Effects of a Pandemic: Facilitating Improved Nursing Home Care Delivery Through Technology Content: The coronavirus disease (COVID-19) pandemic has been particularly challenging for nursing home staff and residents. Centers for Medicare & Medicaid Services regulation waivers are burdening staff and affecting how care is delivered. Residents are experiencing social isolation, which can result in physical and behavioral health issues, particularly for persons with dementia. These challenges can be addressed in part through technology adaptations. Full integration of electronic health record systems can improve workflow and care quality. Telehealth can improve access to outside providers, provide remote monitoring, and improve social connectedness. Electronic and audiovisual programs can be used for end-of-life planning and information sharing between nursing home staff and families. Online learning systems and other online resources provide flexible options for staff education and training. Investing in and adapting technology can help mitigate workforce stress and improve the quality of nursing home care during and after the COVID-19 crisis.", "qid": 15, "docid": "cbs3f71g", "rank": 81, "score": 6.1981000900268555}, {"content": "Title: The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach Content: The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states.", "qid": 15, "docid": "ysa8vb9x", "rank": 82, "score": 6.192800045013428}, {"content": "Title: Life\u2010history traits predict perennial species response to fire in a desert ecosystem Content: The Mojave Desert of North America has become fire\u2010prone in recent decades due to invasive annual grasses that fuel wildfires following years of high rainfall. Perennial species are poorly adapted to fire in this system, and post\u2010fire shifts in species composition have been substantial but variable across community types. To generalize across a range of conditions, we investigated whether simple life\u2010history traits could predict how species responded to fire. Further, we classified species into plant functional types (PFTs) based on combinations of life\u2010history traits and evaluated whether these groups exhibited a consistent fire\u2010response. Six life\u2010history traits varied significantly between burned and unburned areas in short (up to 4 years) or long\u2010term (up to 52 years) post\u2010fire datasets, including growth form, lifespan, seed size, seed dispersal, height, and leaf longevity. Forbs and grasses consistently increased in abundance after fire, while cacti were reduced and woody species exhibited a variable response. Woody species were classified into three PFTs based on combinations of life\u2010history traits. Species in Group 1 increased in abundance after fire and were characterized by short lifespans, small, wind\u2010dispersed seeds, low height, and deciduous leaves. Species in Group 2 were reduced by fire and distinguished from Group 1 by longer lifespans and evergreen leaves. Group 3 species, which also decreased after fire, were characterized by long lifespans, large non\u2010wind dispersed seeds, and taller heights. Our results show that PFTs based on life\u2010history traits can reliably predict the responses of most species to fire in the Mojave Desert. Dominant, long\u2010lived species of this region possess a combination of traits limiting their ability to recover, presenting a clear example of how a novel disturbance regime may shift selective environmental pressures to favor alternative life\u2010history strategies.", "qid": 15, "docid": "squyqflj", "rank": 83, "score": 6.184199810028076}, {"content": "Title: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China Content: Background: Cases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Methods: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test. Results: Of the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 &ldquo:generations\u201d was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy. Conclusions: Family but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.", "qid": 15, "docid": "ti9b1etu", "rank": 84, "score": 6.149799823760986}, {"content": "Title: Measles-derived vaccines to prevent emerging viral diseases Content: Abstract Infectious disease epidemics match wars and natural disasters in their capacity to threaten lives and damage economies. Like SARS previously and Zika recently, the Ebola crisis in 2015 showed how vulnerable the world is to these epidemics, with over 11,000 people dying in the outbreak. In addition to causing immense human suffering, these epidemics particularly affect low- and middle-income countries. Many of these deadly infectious diseases that have epidemic potential can become global health emergencies in the absence of effective vaccines. But very few vaccines against these threats have been developed to create proven medical products. The measles vaccine is an efficient, live attenuated, replicating virus that has been safely administered to 2 billion children over the last 40 years, affording life-long protection after a single dose. Taking advantage of these characteristics, this attenuated virus was transformed into a versatile chimeric or recombinant vaccine vector with demonstrated proof-of-principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Clinical trials have shown the safety and immunogenicity of this vaccine platform in individuals with preexisting immunity to measles. This review describes the potential of this platform to develop new vaccines against emerging viral diseases.", "qid": 15, "docid": "uk5khcoz", "rank": 85, "score": 6.138500213623047}, {"content": "Title: CHAPTER 13 FERRETS Content: Publisher Summary This chapter familiarizes veterinarians with basic knowledge of ferret biology, medicine, surgery, and care. Ferrets have a long, slender body with short muscular legs, a long thin tail, small eyes, and short ears. The life span of the ferret is 5 to 8 years. Ferrets may be housed singly or in groups, inside or outside of a house. When kept outdoors, however, they must be protected from extreme weather. Ferrets have difficulty tolerating temperatures above 90\u00b0F or below 20\u00b0F, and appropriate precautions must be taken to prevent their exposure to these extremes. Ferrets are carnivorous and require a suitable diet. A diet that is high in good-quality animal protein and fat and low in complex carbohydrates and fiber is recommended. Ferrets are routinely immunized against canine distemper virus (CDV) and rabies virus. Ferrets are quite susceptible to CDV, and there is a 100% mortality rate in unvaccinated ferrets infected with CDV. When a new ferret is brought into the household, a quarantine period is recommended before introducing it to other animals, particularly other ferrets. The purpose of the quarantine period is to identify and prevent transmission of infectious disease potentially carried by the new ferret. The duration of this period allows for the development of any clinical signs in a seemingly healthy ferret following entrance into the new household.", "qid": 15, "docid": "mkk3uuv4", "rank": 86, "score": 6.129000186920166}, {"content": "Title: The epidemic consequences of virulence and free-living survival relationships in models of emerging outbreaks Content: The relationship between parasite virulence and transmission is a pillar of evolutionary theory that has specific implications for public health. Part of this canon involves the idea that virulence and free-living survival (a key component of transmission) may have different relationships in different host-parasite systems. Most examinations of the evolution of virulence-transmission relationships\u2014theoretical or empirical in nature\u2014tend to focus on the evolution of virulence, with transmission a secondary consideration. In virus evolution, recent studies have examined how the evolution of free-living survival can influence other traits. However, few studies have examined the epidemic-scale consequences of evolution across the different virulence-survival relationships, and specifically, of increased free-living survival. In this study, we utilize a mathematical model motivated by aspects of SARS-CoV-2 natural history to investigate how evolutionary changes in survival traits, and their subsequent relationship to virulence traits, may influence several aspects of disease dynamics. Specifically, we examine how each of two different hypothesized relationships between virulence and survival, one deemed \u201cthe Curse of the Pharaoh hypothesis\u201d and the other more classically referred to as the \u201ctradeoff hypothesis.\u201d Across virulence-survival frameworks, we found that small changes (5% above and below the nominal value) in survival can have a meaningful effect on certain outbreak features, including the R0, and the size of the infectious peak in the population. These results highlight the importance of properly understanding the relationship between virulence and parasite survival, as they offer considerably different predictions for how the evolution of free-living survival will influence the trajectory of an emerging epidemic.", "qid": 15, "docid": "a183x67w", "rank": 87, "score": 6.125400066375732}, {"content": "Title: Studying health-related internet and mobile device use using web logs and smartphone records Content: Many people use the internet to seek information that will help them understand their body and their health. Motivations for such behaviors are numerous. For example, users may wish to figure out a medical condition by searching for symptoms they experience. Similarly, they may seek more information on how to treat conditions they have been diagnosed with or seek resources on how to live a healthy life. With the ubiquitous availability of the internet, searching and finding relevant information is easier than ever before and a widespread phenomenon. To understand how people use the internet for health-related information, we use data from a sample of 1,959 internet users. A unique combination of data containing four months of users\u2019 browsing histories and mobile application use on computers and mobile devices allows us to study which health websites they visited, what information they searched for and which health applications they used. Survey data inform us about users\u2019 socio-demographic background, medical conditions and other health-related behaviors. Results show that women, young users, users with a university education and nonsmokers are most likely to use the internet and mobile applications for health-related purposes. On search engines, internet users most frequently search for pharmacies, symptoms of medical conditions and pain. Moreover, users seem most interested in information on how to live a healthy life, alternative medicine, mental health and women\u2019s health. With this study, we extend the field\u2019s understanding of who seeks and consumes health information online, what users look for as well as how individuals use mobile applications to monitor their health. Moreover, we contribute to methodological research by exploring new sources of data for understanding humans, their preferences and behaviors.", "qid": 15, "docid": "o8gy5zul", "rank": 88, "score": 6.110599994659424}, {"content": "Title: The role of an Orthopaedic Surgeon in the time of Covid-19 Pandemic\u2013a German perspective Content: Covid-19 is a non-orthopaedic disease but is affecting the community of Orthopaedics as much as every part of our daily living. In this Editorial the different aspects of changes in our routine are described, based on the experience of this Editor in Germany. I will try to give you a bit of background information first, as the situation is very much dependent on the specific phase of the pandemic and your place of work. The experience for an Orthopaedic Surgeon in New York or Madrid may differ from that of an Orthopaedic Surgeon in Singapore, or South Korea. As Europe is, at least at the moment, the most affected continent, it hopefully is an interesting topic for all of you. The Covid-19 pandemic is affecting all aspects of our lives, therefore this editorial is divided into 4 sessions: Role as surgeon, as doctor, as teacher, and as family member. Most countries have stopped elective surgeries and by that relegated Orthopaedic surgeons to a minimum of work. Keeping contact to patients with digital tools might be an option to achieve an organised restart after the end of the lock down period and to keep treating patients through that phase. For many Orthopaedic surgeons, the principal task now is being part of an interdisciplinary team that is headed by colleagues from Internal Medicine or Anaesthesiology. Wards from the Orthopaedic department are reorganised as quarantine wards for Covid-19 patients. Worldwide all conferences have been cancelled and nobody knows for how long this will continue. Education now has become fully digital, allowing to present and communicate without real limitations compared to conventional conferences. Some teaching options, such as hands-on workshops, fellowships, etc. are ceased and cannot be replaced by digital options. Due to social distancing families are spending much more time together than before, while some family members, especially the people at risk (elders, ones with a fragile health) cannot be visited for a long time. Get togethers with friends as well as community meetings are completely suspended. For some of them, digital technology is the only option to minimize the problem of social distancing. Overall, it has to be stated, that all parts of our lives as an Orthopaedic Surgeon are affected by the Covid-19 pandemic. As nobody knows how long these restrictions need to remain in place we have to accept them and work on improving this specific situation by following the rules. Hopefully, a vaccine will be developed in the near future, allowing us to return to a \u201cnormal\u201d life. Nevertheless, it will never be like it was before.", "qid": 15, "docid": "lcyv211y", "rank": 89, "score": 6.105999946594238}, {"content": "Title: Impact of COVID-19 pandemic on people living with visual disability. Content: People living with visual disabilities/impairment are more likely vulnerable to get contracted from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV 2) than people without visual impairment. This means more than 253 million people globally will be at higher risk of affecting by the COVID-19. The current pandemic, followed by a nationwide emergency lockdown to slow the unprecedented spread of the virus, will have a serious impact on people living with visual disabilities and even endangers their lives in the long run. Many restrictive and control measures, including the adoption of new behavioural changes (for example, social distance during outdoor movement, limiting touch or tactile contact) recommended by the government will pose immense challenges to individuals with a visual loss. This serious impact, including challenges in healthcare access, can be minimized through inclusive service approaches, involving persons with visual disabilities, caregivers, family members, and healthcare providers, along with the community to a large extent, and finally, support to improve the overall outcomes. The government, along with profit or non-profit private sectors, should consider initiating such inclusive approaches while planning responses to the pandemic. Indeed, the present COVID-19 pandemic provides an opportunity for health care planners and decision-makers of various organizations across India for a reformation of disabilities care. Impacts due to the pandemic and lockdown can be reduced substantially if planning and policy are in place before any emergency happened in the future.", "qid": 15, "docid": "5bb9xeh3", "rank": 90, "score": 6.097899913787842}, {"content": "Title: Impact of COVID-19 pandemic on people living with visual disability Content: People living with visual disabilities/impairment are more likely vulnerable to get contracted from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV 2) than people without visual impairment. This means more than 253 million people globally will be at higher risk of affecting by the COVID-19. The current pandemic, followed by a nationwide emergency lockdown to slow the unprecedented spread of the virus, will have a serious impact on people living with visual disabilities and even endangers their lives in the long run. Many restrictive and control measures, including the adoption of new behavioural changes (for example, social distance during outdoor movement, limiting touch or tactile contact) recommended by the government will pose immense challenges to individuals with a visual loss. This serious impact, including challenges in healthcare access, can be minimized through inclusive service approaches, involving persons with visual disabilities, caregivers, family members, and healthcare providers, along with the community to a large extent, and finally, support to improve the overall outcomes. The government, along with profit or non-profit private sectors, should consider initiating such inclusive approaches while planning responses to the pandemic. Indeed, the present COVID-19 pandemic provides an opportunity for health care planners and decision-makers of various organizations across India for a reformation of disabilities care. Impacts due to the pandemic and lockdown can be reduced substantially if planning and policy are in place before any emergency happened in the future.", "qid": 15, "docid": "gndc1pst", "rank": 91, "score": 6.097898960113525}, {"content": "Title: Biomedical Research in Times of Emergency: Lessons From History Content: Coronavirus disease 2019 has disrupted the lives of billions of persons worldwide. Emergencies can stimulate substantial investment of resources that catalyze impressive scientific accomplishments but can also lead to false promises and ethical breaches. The authors discuss how history shows the importance of treating early results with caution, because we are only beginning to understand severe acute respiratory syndrome coronavirus 2.", "qid": 15, "docid": "l7qdepsp", "rank": 92, "score": 6.093999862670898}, {"content": "Title: Living with the new coronavirus: How can a society cope with uncertainty Content:", "qid": 15, "docid": "aodv8w1i", "rank": 93, "score": 6.084199905395508}, {"content": "Title: Living with the new coronavirus: How can a society cope with uncertainty. Content:", "qid": 15, "docid": "ppxt4xg8", "rank": 94, "score": 6.084198951721191}, {"content": "Title: Singing Away the Social Distancing Blues: Art Therapy in a Time of Coronavirus Content: This essay explores the abundance of art flourishing as a therapeutic antidote to the COVID-19 pandemic and panic arising across the world. Specifically, I discuss how the act of viewing, making, and sharing music, street art, paintings, graphic art, cinema, and digital videos can serve as a therapeutic vehicle for empowerment, solidarity, and collective action as most human beings strive to adopt practices of extreme social distancing as the recommended community mitigation strategy to help save lives before a vaccine is developed. This essay explores how therapeutic art-making can promote physical, mental, and social health at a time in history when all of these are under threat by COVID-19. I root these claims in theoretical literature from art therapy, as well as in inspiring and heart-warming examples of the beautiful coronavirus art that has already begun to fill our digital landscape with motivation, resiliency, and hope, though the crisis is still in its early stages.", "qid": 15, "docid": "g9ckz1tb", "rank": 95, "score": 6.067599773406982}, {"content": "Title: Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV Content: The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.", "qid": 15, "docid": "chl7ykkc", "rank": 96, "score": 6.0609002113342285}, {"content": "Title: Effects of body tilt on multifrequency admittance tympanometry. Content: INTRODUCTION Hydrops and abnormalities of inner fluid pressure are involved in some otologic diseases such as M\u00e9ni\u00e8re's disease (MD). However, demonstrating abnormal perilymphatic or endolymphatic pressure is challenging. Multifrequency tympanometry studies in MD patients demonstrated an increase of the width of conductance tympanograms (outside an attack) compared with controls. To confirm that the increase in conductance width is caused by hyperpressure and not hypopressure in these patients tested outside an attack, we assessed the effect of changes in inner ear fluid pressure caused by body tilt on the results of multifrequency admittancemetry tympanograms. MATERIALS AND METHODS A multifrequency tympanometry including conductance (G) tympanogram at 2 kHz and resonance frequency measurements were performed in 20 volunteers (40 ears) free of otologic or neurologic disease. The measures were collected in three different positions: vertical, supine, and Trendelenburg positions. RESULTS Changes in inner ear fluid pressure caused by body tilt induced an increase in the width of G tympanograms. In the vertical position, the mean value was 141.7 \u00b1 56.5 daPa; in the supine position, it increased to 158 \u00b1 58.3 daPa; and increased even more in the Trendelenburg position (20 degrees), with a mean of 184 \u00b1 69.6 daPa (p < 0.01). Resonance frequency also increased in the Trendelenburg position.We conclude that the increased width of G tympanograms in MD patients outside an attack may be caused by an increase in inner ear fluid pressure.", "qid": 15, "docid": "zpmdrh4q", "rank": 97, "score": 6.049499988555908}, {"content": "Title: Strategies and Solutions for Team Sports Athletes in Isolation due to COVID-19 Content: In December of 2019, there was an outbreak of a severe acute respiratory syndrome caused by the Coronavirus 2 (SARS-CoV-2 or COVID-19) in China. The virus rapidly spread into the whole World causing an unprecedented pandemic and forcing governments to impose a global quarantine, entering an extreme unknown situation. The organizational consequences of quarantine/isolation are: absence of organized training and competition, lack of communication among athletes and coaches, inability to move freely, lack of adequate sunlight exposure, inappropriate training conditions. Based on the current scientific, we strongly recommend encouraging the athlete to reset their mindset to understand quarantine as an opportunity for development, organizing appropriate guidance, educating and encourage athletes to apply appropriate preventive behavior and hygiene measures to promote immunity and ensuring good living isolation conditions. The athlete\u2019s living space should be equipped with cardio and resistance training equipment (portable bicycle or rowing ergometer). Some forms of body mass resistance circuit-based training could promote aerobic adaptation. Sports skills training should be organized based on the athlete\u2019s needs. Personalized conditioning training should be carried out with emphasis on neuromuscular performance. Athletes should also be educated about nutrition (Vitamin D and proteins) and hydration. Strategies should be developed to control body composition. Mental fatigue should be anticipated and mental controlled. Adequate methods of recovery should be provided. Daily monitoring should be established. This is an ideal situation in which to rethink personal life, understanding the situation, that can be promoted in these difficult times that affect practically the whole world.", "qid": 15, "docid": "qwdjb7vk", "rank": 98, "score": 6.038000106811523}, {"content": "Title: Editorial Perspective: COVID\u201019 pandemic\u2010related psychopathology in children and adolescents with mental illness Content: The coronavirus disease (COVID\u201019) pandemic is likely to have negative health consequences way beyond those caused by the virus per se \u2013 including significant psychological distress. Children and adolescents who already live with a mental illness may be particularly vulnerable to the distress associated with the pandemic \u2013 due to, for example, fear of the virus as well as the significant societal changes launched to minimize spread of the virus (social distancing and quarantine). In this editorial perspective, we (a) provide data on COVID\u201019 pandemic\u2010related psychopathology in children and adolescents from a large psychiatric treatment setting in Denmark, (b) give advice on how the likely harmful effects of the COVID\u201019 pandemic on the mental health of children and adolescents may be minimized, and (c) propose six lines of research into pandemic\u2010related psychopathology with emphasis on children and adolescents. Finally, we underline the necessity of politicians, health authorities, and funding bodies supporting these research initiatives here and now.", "qid": 15, "docid": "21bghq0n", "rank": 99, "score": 6.034900188446045}, {"content": "Title: A focus on CORONA VIRUS (COVID-19) Content: The coronavirus episode is a worldwide concern. As time passes, the circumstance appears to change for the most noticeably terrible. An ever-increasing number of individuals are affirmed as contaminated, the death rate goes up somewhat with each deadly case and the infection is advancing outside the Chinese outskirts. The news outlets are everywhere throughout the point, giving day by day or even hourly updates to the inexorably critical circumstance. Be that as it may, most articles and reports appear to concentrate more on instigating alarm and making disarray as opposed to giving an account of log-ical realities or advancing avoidance measures Along these lines, for this arti-cle, how about we leave the frenzy aside and see where that brings us. The Wuhan infection is the main significant wellbeing danger of 2020, yet it\u2019s a long way from being the first or the most noticeably awful wellbeing emergency that humankind confronted. Before we had the Ebola infection, Avian flu and SARS, with the keep goisecng on this rundown, really being a kind of coro-navirus. All were profoundly infectious and possibly savage, yet none caused such an instinctive response from the populace. Regardless of whether we dis-miss those, we have the basic influenza infection that causes a large number of passing right off the bat, and we don\u2019t hear much about that in the news, isn\u2019t that right?.", "qid": 15, "docid": "4a8a118f", "rank": 100, "score": 6.0320000648498535}]}
{"query": "how long does coronavirus remain stable  on surfaces?", "hits": [{"content": "Title: How long does Coronavirus survive on different surfaces? Content: Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices", "qid": 16, "docid": "7ftq02ev", "rank": 1, "score": 8.854900360107422}, {"content": "Title: A Study of Nonstructural Protein 1 of SARS Coronavirus Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) encoded nonstructural protein 1 (nsp1) orchestrates a multi-pronged mechanism to down regulate host gene expression, also known as host shutoff Nsp1 is a 180 amino acid long protein with primarily flexible structure that allows nsp1 to interact with various cellular factors during host shutoff to inhibit translation and promote mRNA decay Mutations of the surface residues of nsp1 either attenuates or augments its host shutoff function prompting the hypothesis that these residues bind cellular proteins that facilitate nsp1 during host shutoff To identify cellular proteins that interact with nsp1 and assist its function, we conducted a quantitative proteomics experiment by comparing protein complexes associated with nsp1 and its inactive mutant (K164AH165A) and computer modeling to predict structural changes By comparing protein complexes, we identified a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts nuclear-cytoplasmic transport of biomolecules Expression of nsp1 in 293 cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation of the protein while other nucleoporins and the nuclear lamina remain unperturbed, suggesting a significant alteration of the nuclear pore complex in the presence of nsp1 However, expression of mutant nsp1, which does not bind to Nup93, does not alter the nuclear pore complex To better understand the structural basis of this protein?s function, we have utilized computational modeling tools, more specifically, I-TASSER (Iterative Threading ASSEmbly Refinement) Structural models of various mutants of nsp1 were obtained (by using I-TASSER) in order to explore the structural impact of different mutations Our preliminary explorations show significant topological changes on nsp1?s surface for specific mutations These perturbations of surface properties can provide a steric-based mechanism of interfering with nsp1?s binding or recognition function therefore, aggravating its host shutoff function", "qid": 16, "docid": "ozc3dh7c", "rank": 2, "score": 8.399800300598145}, {"content": "Title: Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily Content: Frequently touched surfaces of a university classroom that is cleaned daily contained viable human coronavirus 229E (CoV-229E). Tests of a CoV-229E laboratory strain under conditions that simulated the ambient light, temperature, and relative humidity conditions of the classroom revealed that some of the virus remained viable on various surfaces for 7 days, suggesting CoV-229E is relatively stable in the environment. Our findings reinforce the notion that contact transmission may be possible for this virus.", "qid": 16, "docid": "khpc9f98", "rank": 3, "score": 8.037199974060059}, {"content": "Title: Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing Content: A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4C, 22C, and 37C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4C (14 days). Virus remained stable on skin for at least 96 h at 22C and for at least 8h at 37C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22C and 4 h at 37C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4C and at least 4 h at 22C. No viable virus was detected on clothing samples at 37C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.", "qid": 16, "docid": "ywusapij", "rank": 4, "score": 7.853000164031982}, {"content": "Title: In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata. Content: How does the concerted activity of neuronal populations shape behavior? Impediments to address this question are primarily due to critical experimental barriers. An integrated perspective on large scale neural information processing requires an in vivo approach that can combine the advantages of exhaustively observing all neurons dedicated to a given type of stimulus, and simultaneously achieve a resolution that is precise enough to capture individual neuron activity. Current experimental data from in vivo observations are either restricted to a small fraction of the total number of neurons, or are based on larger brain volumes but at a low spatial and temporal resolution. Consequently, fundamental questions as to how sensory information is represented on a population scale remain unanswered. In Drosophila melanogaster, the mushroom body (MB) represents an excellent model to analyze sensory coding and memory plasticity. In this work, we present an experimental setup coupled with a dedicated computational method that provides in vivo measurements of the activity of hundreds of densely packed somata uniformly spread in the MB. We exploit spinning-disk confocal 3D imaging over time of the whole MB cell body layer in vivo while it is exposed to olfactory stimulation. Importantly, to derive individual signal from densely packed somata, we have developed a fully automated image analysis procedure that takes advantage of the specificities of our data. After anisotropy correction, our approach operates a dedicated spot detection and registration over the entire time sequence to transform trajectories to identifiable clusters. This enabled us to discard spurious detections and reconstruct missing ones in a robust way. We demonstrate that this approach outperformed existing methods in this specific context and made possible high-throughput analysis of approximately 500 single somata uniformly spread over the MB in various conditions. Applying this approach, we find that learned experiences change the population code of odor representations in the MB. After long-term memory (LTM) formation, we quantified an increase in responsive somata count and a stable single neuron signal. We predict that this method, which should further enable studying the population pattern of neuronal activity, has the potential to uncover fine details of sensory processing and memory plasticity.", "qid": 16, "docid": "nkbze64q", "rank": 5, "score": 7.768099784851074}, {"content": "Title: In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata Content: How does the concerted activity of neuronal populations shape behavior? Impediments to address this question are primarily due to critical experimental barriers. An integrated perspective on large scale neural information processing requires an in vivo approach that can combine the advantages of exhaustively observing all neurons dedicated to a given type of stimulus, and simultaneously achieve a resolution that is precise enough to capture individual neuron activity. Current experimental data from in vivo observations are either restricted to a small fraction of the total number of neurons, or are based on larger brain volumes but at a low spatial and temporal resolution. Consequently, fundamental questions as to how sensory information is represented on a population scale remain unanswered. In Drosophila melanogaster, the mushroom body (MB) represents an excellent model to analyze sensory coding and memory plasticity. In this work, we present an experimental setup coupled with a dedicated computational method that provides in vivo measurements of the activity of hundreds of densely packed somata uniformly spread in the MB. We exploit spinning-disk confocal 3D imaging over time of the whole MB cell body layer in vivo while it is exposed to olfactory stimulation. Importantly, to derive individual signal from densely packed somata, we have developed a fully automated image analysis procedure that takes advantage of the specificities of our data. After anisotropy correction, our approach operates a dedicated spot detection and registration over the entire time sequence to transform trajectories to identifiable clusters. This enabled us to discard spurious detections and reconstruct missing ones in a robust way. We demonstrate that this approach outperformed existing methods in this specific context and made possible high-throughput analysis of approximately 500 single somata uniformly spread over the MB in various conditions. Applying this approach, we find that learned experiences change the population code of odor representations in the MB. After long-term memory (LTM) formation, we quantified an increase in responsive somata count and a stable single neuron signal. We predict that this method, which should further enable studying the population pattern of neuronal activity, has the potential to uncover fine details of sensory processing and memory plasticity.", "qid": 16, "docid": "tfuj8n9w", "rank": 6, "score": 7.768098831176758}, {"content": "Title: Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces Content: SARS-CoV-2 survives and remains viable on surfaces for several days under different environments as reported in recent studies. However, it is unclear how the viruses survive for such a long time and why their survivability varies across different surfaces. To address these questions, we conduct systematic experiments investigating the evaporation of droplets produced by a nebulizer and human-exhaled gas on surfaces. We found that these droplets do not disappear with evaporation, but instead shrink to a size of a few micrometers (referred to as residues), persist for more than 24 hours, and are highly durable against changes of environmental conditions. The characteristics of these residues change significantly across surface types. Specifically, surfaces with high thermal conductivity like copper do not leave any resolvable residues, while stainless steel, plastic, and glass surfaces form residues from a varying fraction of all deposited droplets at 40% relative humidity. Lowering humidity level suppresses the formation of residues while increasing humidity level enhances it. Our results suggest that these microscale residues can potentially insulate the virus against environmental changes, allowing them to survive inhospitable environments and remain infectious for prolonged durations after deposition. Our findings can also be extended to other viruses transmitted through respiratory droplets (e.g., SARS-CoV, flu viruses, etc.), and can thus lead to practical guidelines for disinfecting surfaces and other prevention measures (e.g., humidity control) for limiting viral transmission.", "qid": 16, "docid": "pdmfxssd", "rank": 7, "score": 7.760799884796143}, {"content": "Title: Long term stability and infectivity of herpesviruses in water Content: For viruses to utilize environmental vectors (hard surfaces, soil, water) for transmission, physical and chemical stability is a prerequisite. There are many factors including pH, salinity, temperature, and turbidity that are known to contribute to the ability of viruses to persist in water. Equine herpesvirus type-1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and wild equids. EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause infections in non-equid animal species, particularly in captive settings. Many of the captive non-equid mammals are not naturally sympatric with equids and do not share enclosures, however, in many cases water sources may overlap. Similarly, in the wild, equids encounter many species at waterholes in times of seasonal drought. Therefore, we hypothesized that EHV-1 is stable in water and that water may act as a vector for EHV-1. In order to establish the conditions promoting or hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in controlled experiments over 21 days. The presence and infectivity of the virus was confirmed by both qPCR and cell culture experiments. Our results show that EHV-1 remains stable and infectious under many conditions in water for up to three weeks.", "qid": 16, "docid": "xwxgvdvp", "rank": 8, "score": 7.509799957275391}, {"content": "Title: Worrying decrease in hospital admissions for myocardial infarction during the COVID-19 pandemic Content: Summary Background: How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. Aims: To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non\u2013ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018\u20132019 and for an unavoidable emergency, i.e. birth. Methods: Based on the national hospitalization database (Programme de m\u00e9dicalisation des syst\u00e8mes d'information [PMSI]), all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. Results: Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018\u20132019 by less than 10%; after the start of lockdown, it decreased by 31% compared with the corresponding time window in 2018\u20132019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. Conclusion: This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.", "qid": 16, "docid": "imusyaot", "rank": 9, "score": 7.370299816131592}, {"content": "Title: Worrying decrease in hospital admissions for myocardial infarction during the COVID-19 pandemic Content: BACKGROUND: How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. AIMS: To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non-ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018-2019 and for an unavoidable emergency, i.e. birth. METHODS: Based on the national hospitalisation database [Programme de m\u00e9dicalisation des syst\u00e8mes d'information (PMSI)], all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. RESULTS: Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018-2019 by less than 10%; after the start of lockdown, it decreased by 31% compared to the corresponding time window in 2018-2019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. CONCLUSION: This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.", "qid": 16, "docid": "o15odm3z", "rank": 10, "score": 7.370298862457275}, {"content": "Title: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Content: Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.", "qid": 16, "docid": "gh58t6eh", "rank": 11, "score": 7.355599880218506}, {"content": "Title: The Ocular Surface and the Coronavirus Disease 2019: Does a Dual \u2018Ocular Route\u2019 Exist? Content: Coronavirus disease 2019 (COVID-19) is an important health problem that was defined as a pandemic by the World Health Organization on 11 March 2020. Although great concern has been expressed about COVID-19 infection acquired through ocular transmission, its underlying mechanism has not currently been clarified. In the current work, we analyzed and elucidated the two main elements that should be taken into account to understand the \u201cocular route\u201d, both from a clinical and molecular point of view. They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein. Although it seems, at the moment, that there is a low risk of coronavirus spreading through tears, it may survive for a long time or replicate in the conjunctiva, even in absence of conjunctivitis signs, indicating that eye protection (e.g., protective goggles alone or in association with face shield) is advisable to prevent contamination from external droplets and aerosol.", "qid": 16, "docid": "g2a4f2ko", "rank": 12, "score": 7.331699848175049}, {"content": "Title: Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine. Content: Highly conserved ectodomain of influenza virus M2 protein (M2e) is an important target for the development of universal influenza vaccines. Today, the use of chemical or genetic fusion constructs have been undertaken to overcome the low immunogenicity of M2e in vaccine formulation. However, current M2e vaccines are neither orally delivered nor heat-stable. In this study, we evaluated the immune efficacy of an orally delivered recombinant M2e vaccine containing 3 molcules of M2e consensus sequence of influenza A viruses, termed RSM2e3. To accomplish this, CotB, a spore coat of Bacillus subtilis (B. subtilis), was used as a fusion partner, and heat-stable nonpathogenic B. subtilis spores were used as the carrier. Our results showed that CotB-M2e3 fusion had no effect on spore structure or function in the resultant recombinant RSM2e3 strain and that heterologous influenza virus M2e protein was successfully displayed on the surface of the recombinant RSM2e3 spore. Importantly, recombinant RSM2e3 spores elicited strong and long-term M2e-specific systemic and mucosal immune responses, completely protecting immunized mice from lethal challenge of A/PR/8/34(H1N1) influenza virus. Taken together, our study forms a solid basis for the development of a novel orally delivered and heat-stable influenza vaccine based on B. subtilis spore surface display.", "qid": 16, "docid": "fkrc17kj", "rank": 13, "score": 7.323800086975098}, {"content": "Title: Bisphosphonate-anchored PEGylation and radiolabeling of superparamagnetic iron oxide: long-circulating nanoparticles for in vivo multimodal (T1 MRI-SPECT) imaging. Content: The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero \u03b6-potential at neutral pH. The longitudinal (r(1)) and transverse (r(2)) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r(1) of 9.5 mM(-1) s(-1) and low r(2)/r(1) ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t(1/2) = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.", "qid": 16, "docid": "g06lthp7", "rank": 14, "score": 7.321300029754639}, {"content": "Title: Traffic-driven epidemic outbreak on complex networks: How long does it take? Content: Recent studies have suggested the necessity to incorporate traffic dynamics into the process of epidemic spreading on complex networks, as the former provides support for the latter in many real-world situations. While there are results on the asymptotic scope of the spreading dynamics, the issue of how fast an epidemic outbreak can occur remains outstanding. We observe numerically that the density of the infected nodes exhibits an exponential increase with time initially, rendering definable a characteristic time for the outbreak. We then derive a formula for scale-free networks, which relates this time to parameters characterizing the traffic dynamics and the network structure such as packet-generation rate and betweenness distribution. The validity of the formula is tested numerically. Our study indicates that increasing the average degree and/or inducing traffic congestion can slow down the spreading process significantly.", "qid": 16, "docid": "wuy3cwhu", "rank": 15, "score": 7.186200141906738}, {"content": "Title: Stability of SARS-CoV-2 on environmental surfaces and in human excreta Content: At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.", "qid": 16, "docid": "ej93duxi", "rank": 16, "score": 7.173099994659424}, {"content": "Title: Structural Considerations in the Fitness Landscape of a Virus Content: Viral fitness is determined by replication within hosts and transmission between them. We examine how pleiotropic mutations that have antagonistic effects (i.e., antibody evasion vs. receptor binding) on viral replication within hosts can impact viral immune escape in the host population. When the host population is vaccinated, the virus escapes from passive immunity by mutations in the antibody-binding region on the surface of the target protein. However, the reduced ability of the antibody to bind the virus is often accompanied by a reduced ability of the virus to bind the cell receptor because the antibody-binding region overlaps with the receptor-binding domain (RBD). The types of permitted mutations are limited. To investigate the causal relation between a mutation in a viral genome and adaptive evolution of a viral population, we developed a mathematical model that describes the population dynamics of viruses, antibodies, and normal/infected cells within a host. The coefficients describe the binding affinity between the virus and the induced antibody and that between the virus and its receptor. Our knowledge-based index enables us to estimate the effect of a mutation in a binding region on the binding affinity. Using population genetic theory, we evaluated the probability that a mutant is fixed in a host population. The mutations that can be fixed with high probabilities may determine how long a vaccine remains effective. We simulate the adaptive evolution of coronavirus, the etiological agent of severe acute respiratory syndrome, and show that some of mutations in the RBD may have high fixation probabilities in the vaccinated host population.", "qid": 16, "docid": "ywhu66o7", "rank": 17, "score": 7.163700103759766}, {"content": "Title: Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory Content: Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage \u03a6X174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.", "qid": 16, "docid": "f94skuai", "rank": 18, "score": 7.008399963378906}, {"content": "Title: Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory Content: Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage &#934;X174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.", "qid": 16, "docid": "jcq2394b", "rank": 19, "score": 7.00839900970459}, {"content": "Title: A Murine and a Porcine Coronavirus Are Released from Opposite Surfaces of the Same Epithelial Cells Content: Abstract Epithelial cells are important target cells for coronavirus infection. Earlier we have shown that transmissible gastroenteritis coronavirus (TGEV) and mouse hepatitis coronavirus (MHV) are released from different sides of porcine and murine epithelial cells, respectively. To study the release of these viruses from the same cells, we constructed a porcine LLC-PK1 cell line stably expressing the recombinant MHV receptor cDNA (LMR cells). The MHV and TGEV receptor glycoproteins were shown by immunofluorescence to appear at the surface of the cells and to be functional so that the cells were susceptible to both MHV and TGEV infection. Both coronaviruses entered polarized LMR cells only through the apical surface. Remarkably, while the cells remained susceptible to TGEV for long periods, infectability by MHV decreased with time after plating of the cells onto filters. This was not due to a lack of expression of the MHV receptor, since this glycoprotein was still abundant on the apical surface of these cells. TGEV and MHV appeared to exit LMR cells from opposite sides. Whereas TGEV was released preferentially at the apical membrane, MHV was released preferentially at the basolateral surface. These results show that vesicles containing the two coronaviruses are targeted differently in LMR cells. We propose that the viruses are sorted at the Golgi complex into different transport vesicles that carry information directing them to one of the two surface domains. The apical release of TGEV and the basolateral release of MHV might be factors contributing to the difference in virus spread found between TGEV and MHV in their respective natural hosts, the former causing mainly a localized enteric infection, the latter spreading through the body to other organs.", "qid": 16, "docid": "4ziz0llu", "rank": 20, "score": 6.980999946594238}, {"content": "Title: Illuminating pathogen\u2013host intimacy through optogenetics Content: The birth and subsequent evolution of optogenetics has resulted in an unprecedented advancement in our understanding of the brain. Its outstanding success does usher wider applications; however, the tool remains still largely relegated to neuroscience. Here, we introduce selected aspects of optogenetics with potential applications in infection biology that will not only answer long-standing questions about intracellular pathogens (parasites, bacteria, viruses) but also broaden the dimension of current research in entwined models. In this essay, we illustrate how a judicious integration of optogenetics with routine methods can illuminate the host\u2013pathogen interactions in a way that has not been feasible otherwise.", "qid": 16, "docid": "fqdv3ohv", "rank": 21, "score": 6.962699890136719}, {"content": "Title: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Content: Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.", "qid": 16, "docid": "tjplc5j6", "rank": 22, "score": 6.962500095367432}, {"content": "Title: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations Content: The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virion\u2019s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious.", "qid": 16, "docid": "9wfb43gt", "rank": 23, "score": 6.955399990081787}, {"content": "Title: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour Content: Influenza A viruses result in the deaths of hundreds of thousands of individuals worldwide each year. In this study, influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on real data from more than 3500 person-to-person contacts and 127,000 surface touches obtained by video-camera. The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively. For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively. The intranasal dose via fomites of the students\u2019 bodies, belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%, 57.8%, 9.3% and 4.9%, respectively. The intranasal dose does not monotonously increase or decrease with the virus transfer rate between hands and surfaces. Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting. Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.", "qid": 16, "docid": "6yu02snn", "rank": 24, "score": 6.930300235748291}, {"content": "Title: Isolation and trypsin-enhanced propagation of turkey enteric (bluecomb) coronaviruses in a continuous human rectal adenocarcinoma cell line. Content: Turkey enteric coronavirus (TCV) from intestinal contents of diarrheal poults was isolated and serially propagated in HRT-18 cells, an established cell line derived from a human rectal adenocarcinoma. In these cells, TCV induced cytopathic changes, including polykaryocytosis, which depended on trypsin in the medium and incubation at 41 C. Viral antigens could be demonstrated in the cytoplasm by immunofluorescence, and extracellular virus was detected by an ELISA and negative electron microscopy. The cell-free virus had characteristics of TCV: shape, surface projections, buoyant density of 1.18 to 1.20 g/ml in sucrose, and hemagglutination of rat RBC. The one-step growth curve was complete by postinoculation hours 14 to 16, and maximal titers reached 9 to 9.5 log10 TCID50/ml during 5 passages, after which the titer remained stable. Electron microscopic examination of infected cell monolayers revealed budding of typical coronavirus particles through intracytoplasmic membranes and accumulation of complete virus in cytoplasmic vesicles. Late in the infection, aggregated progeny vial particles were detected near the outer surface of infected cells. One-day-old turkey poults inoculated orally with tissue culture-adapted TCV isolates developed mild to severe diarrhea.", "qid": 16, "docid": "1fjrzpnr", "rank": 25, "score": 6.928500175476074}, {"content": "Title: The use of comb-type copolymers to sustain the surface bactericidal effect of highly water-soluble cationic biocides Content: A series of free radical comb-type acrylic copolymers was prepared in a solution incorporating charged and/or neutral stabilising species on the backbone. The polymer solutions were formulated with cationic biocides to give physically stable formulations with a long shelf life. Furthermore, through the control of polymer architecture of both the side-chain and the backbone, hydrophobicity, a controlled release of a biocide could be achieved. This technology has resulted in the design of temporary coatings demonstrating a sustained surface disinfecting effect. In laboratory trials, coated surfaces with polymeric/biocidal formulations continued to show a disinfection effect after several washes.", "qid": 16, "docid": "nsn7m590", "rank": 26, "score": 6.92710018157959}, {"content": "Title: Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization Content: The rodent arenavirus glycoprotein complex encodes a stable signal peptide (SSP) that is an essential structural component of mature virions. The SSP, GP1, and GP2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity. Nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (ER) to cleave SSP from the remaining precursor GP1/2 (glycoprotein complex [GPC]) glycoprotein and second within the Golgi stacks by the cellular SKI-1/S1P for GP1/2 processing to yield GP1 and GP2 subunits. Cleaved SSP is not degraded but retained as an essential glycoprotein subunit. Here, we defined functions of the 58-amino-acid lymphocytic choriomeningitis virus (LCMV) SSP in regard to glycoprotein complex processing and maturation. Using molecular biology techniques, confocal microscopy, and flow cytometry, we detected SSP at the plasma membrane of transfected cells. Further, we identified a sorting signal (FLLL) near the carboxyl terminus of SSP that is required for glycoprotein maturation and trafficking. In the absence of SSP, the glycoprotein accumulated within the ER and was unable to undergo processing by SKI-1/S1P. Mutation of this highly conserved FLLL motif showed impaired glycoprotein processing and secretory pathway trafficking, as well as defective surface expression and pH-dependent membrane fusion. Immunoprecipitation of SSP confirmed an interaction between the signal peptide and the GP2 subunit; however, mutations within this FLLL motif disrupted the association of the GP1 subunit with the remaining glycoprotein complex.", "qid": 16, "docid": "wbh06gzb", "rank": 27, "score": 6.9166998863220215}, {"content": "Title: Quantitative temporal\u2010spatial distribution of severe acute respiratory syndrome\u2010associated coronavirus (SARS\u2010CoV) in post\u2010mortem tissues Content: Few post\u2010mortem studies have been performed on patients who have died from severe acute respiratory syndrome (SARS). No studies have examined how the SARS\u2010associated coronavirus (SARS\u2010CoV) loads in different organs with respect to time, post\u2010mortem. The aim of this study was to determine the quantitative temporal\u2010spatial distribution of SARS\u2010CoV in the post\u2010mortem tissue samples of seven patients. Quantitation of a house\u2010keeping gene, glyceraldehyde\u20103\u2010phosphate dehydrogenase (GAPDH) was undertaken to standardize the amount of tissue tested. SARS\u2010CoV viral load and SARS\u2010CoV/GAPDH RNA ratio for each organ type were related to four time durations: onset of illness to death, death to post\u2010mortem tissue sampling, and total durations of treatment with ribavirin and hydrocortisone. The SARS\u2010CoV/GAPDH RNA ratio remained relatively stable in most organ tissue types for all these time durations. The ratio reached the highest value of equal to or greater than one for lung and small bowel, whereas those for heart, liver, spleen, and kidney were always less than one. It is concluded that SARS\u2010CoV viral loads in these organs remain relatively stable, post\u2010mortem. This quantitative assessment further supports SARS\u2010CoV has a specific tropism for the human respiratory and gastrointestinal tracts, which may be related to the density of SARS\u2010CoV receptors. J. Med. Virol. 79:1245\u20131253, 2007. \u00a9 Wiley\u2010Liss, Inc.", "qid": 16, "docid": "md0avnqg", "rank": 28, "score": 6.888599872589111}, {"content": "Title: Trunk muscle activation characteristics in patients with severe haemophilia. Content: INTRODUCTION Recurrent bleeding episodes in patients with haemophilia (PWH) lead to joint alterations and therewith disturbed muscle coordination patterns. Major weight-bearing joints are affected most. However, possible effects on trunk muscle activity have not been examined so far. The objective of this work was to study consequences of haemarthropathy on characteristics of trunk muscles in PWH while standing on surfaces with different mechanical properties. METHODS Surface EMG of internal oblique (IO) and multifidus (MF) muscles were bilaterally recorded during a natural bilateral stance in 20 PWH with severe haemophilia A [age: 42 years (SD: 10)] and 25 non-haemophilic controls [NHC, 43 (12)]. Amplitude ratios, a symmetry index between sides and the co-activation ratio of IO over MF served as outcome measures and compared standing on three different surfaces (stable, soft, unsteady). RESULTS PWH revealed markedly restricted lower extremity joints (P < 0.001), but without any hint of back pain. Neither result revealed significant main or interaction effects of 'group' (P > 0.24). Group-independent analyses showed amplitude ratios (MF: P < 0.05) as well as symmetry indices (MF: P < 0.02) significantly altered by 'surface' in NHC only. Effects of utilizing soft vs. unsteady surfaces were not detectable (P > 0.77). CONCLUSION Utilizing unstable surfaces does not lead to altered trunk muscle activity in PWH. Differently than expected, a quite similar behaviour of lower trunk muscles in terms of applied indices can be found in PWH and NHC. Ascending alterations of muscle coordination in PWH could not be verified.", "qid": 16, "docid": "8cplu9mi", "rank": 29, "score": 6.8703999519348145}, {"content": "Title: Prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation Content: Mortality in acute respiratory distress syndrome (ARDS) remains unacceptably high at approximately 39%. One of the only treatments is supportive: mechanical ventilation. However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS. Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication. Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated. A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients. Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually \u201cnudge\u201d alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection.", "qid": 16, "docid": "wb150n8w", "rank": 30, "score": 6.817200183868408}, {"content": "Title: Dynamics of HBV surface antigen related endpoints in chronic hepatitis B infection: a systematic review and meta-analysis Content: BACKGROUND: In chronic hepatitis B (CHB) treatment, hepatitis B virus surface antigen (HBsAg) is regarded as a promising clinical endpoint associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg. METHODS: Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various anti-viral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC), or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics. RESULTS: We collected data from 24 papers involving 6674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remain stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7%-7.9%) and NUC+IFN (5.2%, 3.1%-7.4%) were significantly higher than that of NUC (0.93%, 0.29%-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN. CONCLUSIONS: With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.", "qid": 16, "docid": "0mnxx019", "rank": 31, "score": 6.808800220489502}, {"content": "Title: Dynamics of HBV surface antigen related endpoints in chronic hepatitis B infection: a systematic review and meta-analysis. Content: BACKGROUND In chronic hepatitis B (CHB) treatment, hepatitis B virus surface antigen (HBsAg) is regarded as a promising clinical endpoint associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg. METHODS Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various anti-viral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC), or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics. RESULTS We collected data from 24 papers involving 6674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remain stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7%-7.9%) and NUC+IFN (5.2%, 3.1%-7.4%) were significantly higher than that of NUC (0.93%, 0.29%-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN. CONCLUSIONS With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.", "qid": 16, "docid": "77pbhylo", "rank": 32, "score": 6.8087992668151855}, {"content": "Title: Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25. Content: The mechanism for how internal ribosome entry sites (IRESs) recruit ribosomes to initiate translation of an mRNA is not completely understood. We investigated how a 40S subunit was recruited by the cricket paralysis virus intergenic region (CrPV IGR) IRES to form a stable 40S-IRES complex. Kinetic binding studies revealed that formation of the complex between the CrPV IGR and the 40S subunit consisted of two-steps: an initial fast binding step of the IRES to the 40S ribosomal subunit, followed by a slow unimolecular reaction consistent with a conformational change that stabilized the complex. We further showed that the ribosomal protein S25 (eS25), which is required by functionally and structurally diverse IRESs, impacts both steps of the complex formation. Mutations in eS25 that reduced CrPV IGR IRES activity either decreased 40S-IRES complex formation, or increased the rate of the conformational change that was required to form a stable 40S-IRES complex. Our data are consistent with a model in which eS25 facilitates initial binding of the CrPV IGR IRES to the 40S while ensuring that the conformational change stabilizing the 40S-IRES complex does not occur prematurely.", "qid": 16, "docid": "42c532h7", "rank": 33, "score": 6.769000053405762}, {"content": "Title: Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25 Content: The mechanism for how internal ribosome entry sites (IRESs) recruit ribosomes to initiate translation of an mRNA is not completely understood. We investigated how a 40S subunit was recruited by the cricket paralysis virus intergenic region (CrPV IGR) IRES to form a stable 40S-IRES complex. Kinetic binding studies revealed that formation of the complex between the CrPV IGR and the 40S subunit consisted of two-steps: an initial fast binding step of the IRES to the 40S ribosomal subunit, followed by a slow unimolecular reaction consistent with a conformational change that stabilized the complex. We further showed that the ribosomal protein S25 (eS25), which is required by functionally and structurally diverse IRESs, impacts both steps of the complex formation. Mutations in eS25 that reduced CrPV IGR IRES activity either decreased 40S-IRES complex formation, or increased the rate of the conformational change that was required to form a stable 40S-IRES complex. Our data are consistent with a model in which eS25 facilitates initial binding of the CrPV IGR IRES to the 40S while ensuring that the conformational change stabilizing the 40S-IRES complex does not occur prematurely.", "qid": 16, "docid": "zdjpnzvs", "rank": 34, "score": 6.768999099731445}, {"content": "Title: A Functional Link between RNA Replication and Virion Assembly in the Potyvirus Plum Pox Virus. Content: Accurate assembly of viral particles in the potyvirus Plum pox virus (PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in Nicotiana benthamiana leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied in trans, was assembled into virus-like particles and remained stable after in vitro incubation. In contrast, deletions in multiple regions of the LONG coding sequence prevented the CP stabilization mediated by HCPro. In particular, we demonstrated that the first 178 amino acids of P3, but not a specific nucleotide sequence coding for them, are required for CP stability and proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we observed that the subviral LONG RNA replicates and locally spreads in N. benthamiana leaves expressing an RNA silencing suppressor. The analysis of the effect of both point and deletion mutations affecting RNA replication in LONG and full-length PPV demonstrated that this process is essential for the assembly of stable viral particles. Interestingly, in spite of this requirement, the CP produced by a nonreplicating viral RNA can be stably assembled into virions as long as it is coexpressed with a replication-proficient RNA. Altogether, these results highlight the importance of coupling encapsidation to other viral processes to secure a successful infection.IMPORTANCE Viruses of the family Potyviridae are among the most dangerous threats for basically every important crop, and such socioeconomical relevance has made them a subject of many research studies. In spite of this, very little is currently known about proteins and processes controlling viral genome encapsidation by the coat protein. In the case of Plum pox virus (genus Potyvirus), for instance, we have previously shown that the multitasking viral factor HCPro plays a role in the production of stable virions. Here, by using this potyvirus as a model, we move further to show that additional factors are also necessary for the efficient production of potyviral particles. More importantly, a comprehensive screening for such factors led us to the identification of a functional link between virus replication and packaging, unraveling a previously unknown connection of these two key events of the potyviral infection cycle.", "qid": 16, "docid": "zca9qww1", "rank": 35, "score": 6.763500213623047}, {"content": "Title: Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments. Content: tRNA-derived RNA fragments (tRFs) have emerged as a new class of functional RNAs implicated in cancer, metabolic and neurological disorders, and viral infection. Yet our understanding of their biogenesis and functions remains limited. In the present study, through analysis of small RNA profile we have identified a distinct set of tRFs derived from pre-tRNA 3' trailers in the hepatocellular carcinoma cell line Huh7. Among those tRFs, tRF_U3_1, which is a 19-nucleotide-long chr10.tRNA2-Ser(TGA)-derived trailer, was expressed most abundantly in both Huh7 and cancerous liver tissues, being present primarily in the cytoplasm. We show that genetic loss of tRF_U3_1 does not affect cell growth and it is not involved in Ago2-mediated gene silencing. Using La/SSB knockout Huh7 cell lines, we demonstrate that this nuclear-cytoplasmic shuttling protein directly binds to the 3' U-tail of tRF_U3_1 and other abundantly expressed trailers and plays a critical role in their stable cytoplasmic accumulation. The pre-tRNA trailer-derived tRFs capable of sequestering the limiting amounts of La/SSB in the cytoplasm rendered cells resistant to various RNA viruses, which usurp La/SSB with RNA chaperone activity for their gene expression. Collectively, our results establish the trailer-derived tRF-La/SSB interface, regulating viral gene expression.", "qid": 16, "docid": "mgribv9s", "rank": 36, "score": 6.75570011138916}, {"content": "Title: Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. Content: OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.", "qid": 16, "docid": "gp3ib74q", "rank": 37, "score": 6.747499942779541}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare, and respond to COVID-19 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID-19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle-income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time-based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short- and long-term interventions to manage outbreaks at the international, national, and subnational levels in the region.", "qid": 16, "docid": "w5kjmw88", "rank": 38, "score": 6.696400165557861}, {"content": "Title: Bats and Emerging Infections: An Ecological and Virological Puzzle Content: More than 200 viruses have been detected in bats. Some unique bat characteristics can explain the roles played in the maintenance and transmission of viruses: long phylogenetic history can have originated coevolution processes, great number of species are adapted to live in different environments, big mobility, long lifespan and gregarious behaviour of many species. To analyse zoonoses long longitudinal studies are needed with a multidisciplinary approximation to obtain the following eco-epidemiological data: colony size, number of bats per species, population structure, behaviour of each species, degree of contact between bats, social structure, remaining time of bats in the colony, colony type, foraging area, turnover rate of individuals, shelter temperature, relationship with other colonies and co-infection processes. These data allows assessing the epidemiological risk and which preventive measures are necessary to take. The structure and functionality of ecosystems are changing worldwide at an unprecedented rate and can modify the interactions between humans and infected bats. There are more or less local factors that can affect the emergence and spread of diseases (environmental alterations, changes in land use, human population growth, changes in human socioeconomic behavior or social structure, people mobility increase, trade increase, forest fires, extreme weather events, wars, breakdown in public health infrastructure, etc.). Twenty-three percent of all bat species in the world are decreasing. How does the regression of bat species affect the dynamic of viruses? The dichotomy between health risk and bat preservation is compatible with a preventive task based on more information and training.", "qid": 16, "docid": "amzc5yrd", "rank": 39, "score": 6.664400100708008}, {"content": "Title: A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike Content: Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short \u03b1-HCoV and long \u03b2-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.", "qid": 16, "docid": "3c5ab73l", "rank": 40, "score": 6.657400131225586}, {"content": "Title: Characterization of a calf diarrheal coronavirus. Content: A coronavirus-like agent isolated from feces of a calf with diarrhea and attenuated by consecutive passage in a fetal bovine kidney cell line was characterized as a coronavirus. Negatively stained virions were approximately circular, had a mean diameter of 120 nm, and were covered with wide-spaced, petal-shaped projections about 20 nm long. Virions in ultrathin sections of infected cell monolayers had a mean diameter of 80 nm, lacked surface projections, and were found within cytoplasmic vesicles. Viral antigen was demonstrated by immunofluorescence microscopy to occur only in cytoplasm. Growth of the virus was not inhibited by 5-iodo-2'- deoxyuridine and actinomycin D. The virus was sensitive to ether, chloroform, deoxycholate, and heat treatment. However, thermosensitivity was stabilized in the presence of 1 M MgCl2; at pH 3, the virus was stable. Hemadsorption and hemagglutination were observed with erythrocytes of hamsters, mice, and rats but not with erythrocytes of cats, dogs, goats, sheep, cattle, horses, turkeys, chickens, guinea pigs, rabbits, geese, pigs, and man (type O). However, hemadsorption and hemagglutination were shown to be virus specific, since this could be inhibited by specific antiserum. Both infectivity and hemagglutinating activity were maximal at a particle density of 1.18 g/ml by sucrose density gradient centrifugation, indicating that hemagglutinin was part of the virion.", "qid": 16, "docid": "t42ube59", "rank": 41, "score": 6.6442999839782715}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID\u201019 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID\u201019 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time\u2010based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short\u2010 and long\u2010term interventions to manage outbreaks at the international, national and sub\u2010national levels in the region. This article is protected by copyright. All rights reserved.", "qid": 16, "docid": "gan10za0", "rank": 42, "score": 6.625899791717529}, {"content": "Title: Percutaneous thermal ablation of subcapsular hepatocellular carcinomas: influence of tumor-surface contact and protrusion on therapeutic efficacy and safety. Content: PURPOSE To evaluate therapeutic efficacy and complication of percutaneous thermal ablation of subcapsular hepatocellular carcinomas (HCCs), and how these may be influenced by the degree of tumor to liver surface contact and tumor protrusion from liver surface. MATERIALS AND METHODS Our retrospective study was approved by the Institutional Review Board. Between January 2006 and December 2013, 290 patients (82 women, 208 men; mean age, 64.5 years; range, 33-89 years) with 474 subcapsular (within 1 cm to the liver surface) HCCs (mean size, 23.7 mm; range, 6-71 mm) underwent percutaneous thermal ablation. The HCCs were divided into surface contact group (n = 243) and non-surface contact group (n = 231). The former was further subdivided into exophytic and non-exophytic HCCs. Technical success, primary technique efficacy, local tumor progression (LTP), and secondary technique efficacy rates were analyzed and compared by the chi-square test or Fisher exact test. Prognostic factors for LTP and secondary technique efficacy were assessed using the Cox regression model. Major complications were also assessed. RESULTS With median follow-up of 15 months (range, 1-87 months), technical success and primary technique efficacy were 98.7% and 95.7% % in the non-surface contact group; 96.4% and 94.0% in the non-exophytic group; and 100% and 94.7% in the exophytic group (p > 0.05). Tumor size > 3 cm was a significant predictor for LTP, but not for secondary efficacy. Overall major complication rate was 3.8% (24/624) and was not different among the three groups. CONCLUSION Subcapsular HCCs can be effectively treated with thermal ablation techniques. Degree of tumor-surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. KEY POINTS \u2022 Subcapsular HCCs can be effectively treated with thermal therapy when proper image-guided technique and assistive techniques are applied. \u2022 Degree of tumor surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. \u2022 Major complications after percutaneous thermal ablation of subcapsular HCCs such as tumor seeding can be minimized by avoiding breach of the tumor capsule exposed to the peritoneal surface and use of tract ablation.", "qid": 16, "docid": "qztkpinh", "rank": 43, "score": 6.617199897766113}, {"content": "Title: Does COVID19 infect the brain? If so, smokers might be at a higher risk. Content: COVID19 is a devastating global pandemic with epicenters in China, Italy, Spain, and now the United States. While the majority of infected cases appear mild, in some cases individuals present serious cardiorespiratory complications with possible long-term lung damage. Infected individuals report a range of symptoms from headaches to shortness of breath to taste and smell loss. To that end, less is known about the how the virus may impact different organ systems. The SARS-CoV2 virus, which is responsible for COVID19, is highly similar to SARS-CoV. Both viruses have evolved an ability to enter host cells through direct interaction with the angiotensin converting enzyme 2 (ACE2) protein at the surface of many cells. Published findings indicate that SARS-CoV can enter the human nervous system with evidence from both postmortem brains and detection in cerebrospinal fluid of infected individuals. Here we consider the ability of SARS-CoV2 to enter and infect the human nervous system based on the strong expression of the ACE2 target throughout the brain. Moreover, we predict that nicotine exposure through various kinds of smoking (cigarettes, e-cigarettes, or vape) can increase the risk for COVID19 neuroinfection based on known functional interactions between the nicotinic receptor and ACE2. We advocate for higher surveillance and analysis of neuro-complications in infected cases.", "qid": 16, "docid": "rdm2ks69", "rank": 44, "score": 6.611199855804443}, {"content": "Title: Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59. Content: The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.", "qid": 16, "docid": "y53sp8wc", "rank": 45, "score": 6.605100154876709}, {"content": "Title: Partitioning of Viruses in Wastewater Systems and Potential for Aerosolization Content: [Image: see text] To gain insight into the potential for aerosolization of viruses in wastewater systems, we investigated the partitioning of MS2 and Phi6 bacteriophages in synthetic sludge and anaerobically digested sludge from a wastewater treatment plant. We evaluated partitioning among the liquid, solids, and material surfaces of porcelain, concrete, polyvinyl chloride (PVC), and polypropylene. In all cases, at least 94% of the virions partitioned into the liquid fraction. In real sludge, no more than 0.8% of virions partitioned to the solids and no more than 6% to the material surface. Both MS2 and Phi6 partitioned more to the surface of concrete and polypropylene than to the surface of porcelain or PVC. Partitioning of viruses in wastewater among the liquid, biosolids, and material surface does not appear to mitigate the potential for aerosolization of virus, as most of the virus remains in the liquid phase.", "qid": 16, "docid": "onen3aw3", "rank": 46, "score": 6.582099914550781}, {"content": "Title: Surface Nano-patterning of Polymers for Mass-Sensitive Biodetection Content: The crafting of sensor material of desired features has always remained a challenging task in the field of material designing and predominantly becomes more interesting when analyte belongs to biospecies. Label-free detection of different bioanalytes such as enzymes, viruses, microorganisms, and blood groups through mass-sensitive transducers has gained considerable importance in the development of modern biosensors. Analyte molecules interact with the surface of sensitive layer coated on these devices and as a result of this interaction, the frequency change is determined, which provides quantitative information about the mass of analyte. One of the most vital elements of these detection systems is to design selective sensor coatings through control surface structuring at nanoscale. Molecular imprinting has proven to be a highly suitable technique to generate selective surfaces that are capable of detecting different analytes, quantitatively and qualitatively as well. The tailor-made synthetic antibody cavities are rigid and stable, which are not immediately collapsed upon analyte interaction; moreover, the different bioanalytes do not undergo any phase change and maintain their original identity during analysis. This chapter will discuss the contribution of imprinting methods to design optimized surfaces for mass-sensitive detection of diverse biological species.", "qid": 16, "docid": "mmmm3pmv", "rank": 47, "score": 6.564599990844727}, {"content": "Title: Mutual Moral Obligations in the Prevention of Infectious Diseases Content: Not so long ago health policy was about little more than the provision of medical care. The availability of treatment is important for those in need of cure, but by now it is a well-shown fact that health is generally determined to a much greater extent by other factors. Genetic constitution, lifestyle choices and socio-economic environment largely explain why some of us become ill or die earlier than others who remain healthy (Mackenbach 1996; McKeown 1976; Wilkinson and Marmot 2003). While some of these factors fall under the control of an individual, the majority does not. Research increasingly indicates how remarkably sensitive our health seems to be to what has become known as the \u2018social determinants of health\u2019. These factors generally fall beyond the control of an individual, but can nonetheless be influenced on a population level. This causes a shift in the focus of health policy from the classic provision of health care to policies specifically designed to influence the causal factors of ill-health in different non-medical fields. The flipside of that evolution is a significant increase of the state\u2019s influence in the sphere of individual lives. A pertinent question remains the one that asks for the legitimate role of governments in modifying, discouraging or prohibiting behaviors that lead to ill-health. To what extent can and should we hold public policy responsible for us leading a healthy life? Most scholars will argue that governments indeed have a role to play, but that the limits will be reached when public health measures would imply large sacrifices of individual liberty.", "qid": 16, "docid": "pir3xmbw", "rank": 48, "score": 6.480100154876709}, {"content": "Title: COVID-19 and ENT Surgery Content: In Otorhinolaryngology - Head and Neck Surgery, clinical examination and invasive procedures on the respiratory tract and on airway-connected cavities, such as paranasal sinuses and the middle ear, expose people to direct transmission of SARS-CoV-2 by inhalation or ocular projection of contaminated droplets, and to indirect transmission by contact with contaminated hands, objects or surfaces. Estimating an R0 of COVID-19 at around 3 justified postponing non-urgent face-to-face consultations and expanding the use of teleconsultation in order to limit the risks of SARS-CoV-2 infection of patients or health workers and comply with the lockdown. The health authority recommends cancellation of all medical or surgical activities, which are not urgent as long as this does not involve a loss of chance for the patient. The purpose of this cancellation is to significantly increase critical care capacity, prioritise the reception of patients with COVID-19, prioritise the allocation of staff and provision of the equipment necessary for their medical or surgical management, and contribute to the smooth running of downstream critical care within their establishment. Another goal is to reduce the risks of patient contamination within healthcare facilities. This document provides guidance on how to proceed with and adapt ENT surgery in the current pandemic context, as well as on the management of postponed operations. This best practice advice must of course be adapted in each region according to the development of the epidemic and pre-existing arrangements. Their local application can only be decided within the framework of collaboration between the ENT teams, the operational hygiene units and all the other specialties concerned.", "qid": 16, "docid": "gzqtpw6b", "rank": 49, "score": 6.457499980926514}, {"content": "Title: COVID-19 and ENT Surgery Content: ABSTRACT In Otorhinolaryngology - Head and Neck Surgery, clinical examination and invasive procedures on the respiratory tract and on airway-connected cavities such as paranasal sinuses and the middle ear expose people to direct transmission of SARS-CoV-2 by inhalation or ocular projection of contaminated droplets, and to indirect transmission by contact with contaminated hands, objects or surfaces. Estimating an R0 of Covid-19 at around 3 justified postponing non-urgent face-to-face consultations and expanding the use of teleconsultation in order to limit the risks of SARS-CoV-2 infection of patients or health workers and comply with the lockdown. The health authority recommends cancellation of all medical or surgical activities which are not urgent as long as this does not involve a loss of chance for the patient. The purpose of this cancellation is to significantly increase critical care capacity, prioritize the reception of patients with Covid-19, prioritize the allocation of staff and provision of the equipment necessary for their medical or surgical management, and contribute to the smooth running of downstream critical care within their establishment. Another goal is to reduce the risks of patient contamination within healthcare facilities. This document provides guidance on how to proceed with and adapt ENT surgery in the current pandemic context, as well as on the management of postponed operations. This best practice advice must of course be adapted in each region according to the development of the epidemic and pre-existing arrangements. Their local application can only be decided within the framework of collaboration between the ENT teams, the operational hygiene units and all the other specialties concerned.", "qid": 16, "docid": "kec74uka", "rank": 50, "score": 6.457499027252197}, {"content": "Title: The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations Content: Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive. Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single\u2010stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry. The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 \u00b1 16 pN, a duration time of 278 \u00b1 68 ms. The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time. Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.", "qid": 16, "docid": "cxnoemdo", "rank": 51, "score": 6.438600063323975}, {"content": "Title: Minute ventilation during spontaneous breathing, high-intensity noninvasive positive pressure ventilation and intelligent volume assured pressure support in hypercapnic COPD. Content: BACKGROUND High-intensity noninvasive positive pressure ventilation (HI-NPPV) is an effective treatment option in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the effect of HI-NPPV compared with spontaneous breathing (SB) on minute ventilation (MV) in patients receiving long-term treatment remains to be determined. This study compared MV during HI-NPPV and SB. In addition, the ability of intelligent volume assured pressure support (iVAPS) to increase MV to the same extent as HI-NPPV was determined. METHODS Daytime pneumotachographic measurements were performed during SB, HI-NPPV and iVAPS. RESULTS Twenty-seven stable hypercapnic COPD patients (mean FEV1 34 \u00b1 15% predicted) who had been treated with HI-NPPV for a median of 22 months (interquartile range 8.5-84 months) were enrolled. Mean MV was 9.5 \u00b1 1.7 L/min during SB and 12.1 \u00b1 2.8 L/min during HI-NPPV, an increase of 2.5 L/min (95% CI [1.5-3.6] p < 0.001), or 26%. MV during iVAPS was 11.7 \u00b1 3.6 L/min, an increase of 1.8 L/min (95%CI [0.7-3.0], p = 0.003) compared with SB. There was no difference in MV between HI-NPPV and iVAPS (p = 0.25). CONCLUSION Long-term HI-NPPV increased MV by an average of 26% compared with SB in stable hypercapnic COPD patients. A similar increase in MV was observed during use of iVAPS.", "qid": 16, "docid": "y7je28je", "rank": 52, "score": 6.389800071716309}, {"content": "Title: How Should the Rehabilitation Community Prepare for 2019-nCoV? Content: With the novel coronavirus 2019 (2019-nCoV) pandemic spreading quickly in the United States and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so most of the world's population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it is currently mainly social distancing and infection control measures.", "qid": 16, "docid": "5gj4lhdj", "rank": 53, "score": 6.387899875640869}, {"content": "Title: Effects of repeated walking in a perturbing environment: a 4-day locomotor learning study. Content: Previous studies have shown that when subjects repeatedly walk in a perturbing environment, initial movement error becomes smaller, suggesting that retention of the adapted locomotor program occurred (learning). It has been proposed that the newly learned locomotor program may be stored separately from the baseline program. However, how locomotor performance evolves with repeated sessions of walking with the perturbation is not yet known. To address this question, 10 healthy subjects walked on a treadmill on 4 consecutive days. Each day, locomotor performance was measured using kinematics and surface electromyography (EMGs), before, during, and after exposure to a perturbation, produced by an elastic tubing that pulled the foot forward and up during swing, inducing a foot velocity error in the first strides. Initial movement error decreased significantly between days 1 and 2 and then remained stable. Associated changes in medial hamstring EMG activity stabilized only on day 3, however. Aftereffects were present after perturbation removal, suggesting that daily adaptation involved central command recalibration of the baseline program. Aftereffects gradually decreased across days but were still visible on day 4. Separation between the newly learned and baseline programs may take longer than suggested by the daily improvement in initial performance in the perturbing environment or may never be complete. These results therefore suggest that reaching optimal performance in a perturbing environment should not be used as the main indicator of a completed learning process, as central reorganization of the motor commands continues days after initial performance has stabilized.", "qid": 16, "docid": "ao309193", "rank": 54, "score": 6.386099815368652}, {"content": "Title: Trunk extensor fatigue decreases jump height similarly under stable and unstable conditions with experienced jumpers. Content: PURPOSE The purpose of this study was to investigate the effects of back extensor fatigue on performance measures and electromyographic (EMG) activity of leg and trunk muscles during jumping on stable and unstable surfaces. METHODS Before and after a modified Biering-Sorensen fatigue protocol for the back extensors, countermovement (CMJ) and lateral jumps (LJ) were performed on a force plate under stable and unstable (balance pad on the force plate) conditions. Performance measures for LJ (contact time) and CMJ height and leg and trunk muscles EMG activity were tested in 14 male experienced jumpers during 2 time intervals for CMJ (braking phase, push-off phase) and 5 intervals for LJ (-30 to 0, 0-30, 30-60, 60-90, and 90-120 ms) in non-fatigued and fatigued conditions. RESULTS A significant main effect of test (fatigue) (p = 0.007, f = 0.57) was observed for CMJ height. EMG analysis showed a significant fatigue-induced decrease in biceps femoris and gastrocnemius activity with CMJ (p = 0.008, f = 0.58 andp = 0.04, f = 0.422, respectively). LJ contact time was not affected by fatigue or surface interaction. EMG activity was significantly lower in the tibialis anterior with LJ following fatigue (p = 0.05, f = 0.405). A test x surface (p = 0.04, f = 0.438) interaction revealed that the non-fatigued unstable CMJ gastrocnemius EMG activity was lower than the non-fatigued stable condition during the onset-of-force phase. CONCLUSION The findings revealed that fatiguing the trunk negatively impacts CMJ height and muscle activity during the performance of CMJs. However, skilled jumpers are not additionally affected by a moderately unstable surface as compared to a stable surface.", "qid": 16, "docid": "chhwtlwy", "rank": 55, "score": 6.383500099182129}, {"content": "Title: Long-term results of simplified frozen elephant trunk technique in complicated acute type A aortic dissection: A case-control study. Content: AIM To describe the long-term experience of a simplified frozen elephant trunk technique (sFETT) used in complicated acute type A aortic dissection (AAAD) treatment. METHODS AND RESULTS Between January 2001 and December 2012, 34 patients (mean age 59.9 \u00b1 11.0 years) with complicated AAAD (DeBakey I) underwent an emergency surgery including sFETT. sFETT consisted in gluing the dissected aortic arch wall layers with gelatine-resorcinol adhesive and video-assisted antegrade open arch aortic stent-graft deployment in the arch or proximal descending aorta. In addition to sFETT, the aortic root was addressed with standard techniques. A 30-day mortality was 14.7% (five patients) due to bleeding (1), multiple organ failure (2), and colon ischemia (2). Postoperative morbidity included neurological (2), renal (1) and cardio-pulmonary complications (4), as well as wound infection (1). Mean follow-up was 74.4 \u00b1 45.0 months. Actual survival rates were 73.5% at 1 year, 70.2% at 5 years, and 58.5% at 13 years of follow-up. Six patients died during long-term follow-up from heart failure (1) and unknown reasons (5). Five patients required reoperation for aortic arch (3) or aorto-iliac (2) progression of aneurysm during the mid- and long-term follow-up. The remaining patients showed favorable evolution of the dissected aorta with false lumen occlusion in most cases and stable aortic diameters. CONCLUSIONS In AAAD patients, sFETT as used in our series is an easy and safe technique to repair the aortic arch. Long-term results after sFETT showed false lumen occlusion and stable aortic diameter in up to 13 years of follow-up.", "qid": 16, "docid": "kgo6e4ei", "rank": 56, "score": 6.368100166320801}, {"content": "Title: Hemodynamic-morphological discriminant models for intracranial aneurysm rupture remain stable with increasing sample size. Content: BACKGROUND We previously established three logistic regression models for discriminating intracranial aneurysm rupture status based on morphological and hemodynamic analysis of 119 aneurysms. In this study, we tested if these models would remain stable with increasing sample size, and investigated sample sizes required for various confidence levels (CIs). METHODS We augmented our previous dataset of 119 aneurysms into a new dataset of 204 samples by collecting an additional 85 consecutive aneurysms, on which we performed flow simulation and calculated morphological and hemodynamic parameters, as done previously. We performed univariate significance tests on these parameters, and multivariate logistic regression on significant parameters. The new regression models were compared against the original models. Receiver operating characteristics analysis was applied to compare the performance of regression models. Furthermore, we performed regression analysis based on bootstrapping resampling statistical simulations to explore how many aneurysm cases were required to generate stable models. RESULTS Univariate tests of the 204 aneurysms generated an identical list of significant morphological and hemodynamic parameters as previously (from the analysis of 119 cases). Furthermore, multivariate regression analysis produced three parsimonious predictive models that were almost identical to the previous ones, with model coefficients that had narrower CIs than the original ones. Bootstrapping showed that 10%, 5%, 2%, and 1% convergence levels of CI required 120, 200, 500, and 900 aneurysms, respectively. CONCLUSIONS Our original hemodynamic-morphological rupture prediction models are stable and improve with increasing sample size. Results from resampling statistical simulations provide guidance for designing future large multi-population studies.", "qid": 16, "docid": "907b8o0m", "rank": 57, "score": 6.366199970245361}, {"content": "Title: Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease Content: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002\u20132003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-\u0394E or SARS-CoV-\u0394[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-\u0394E and rSARS-CoV-\u0394[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-\u0394E is an efficacious vaccine candidate that might be useful if SARS recurred.", "qid": 16, "docid": "8b4n6tm8", "rank": 58, "score": 6.338799953460693}, {"content": "Title: Nanoyeast and Other Cell Envelope Compositions for Protein Studies and Biosensor Applications Content: [Image: see text] Rapid progress in disease biomarker discovery has increased the need for robust detection technologies. In the past several years, the designs of many immunoaffinity reagents have focused on lowering costs and improving specificity while also promoting stability. Antibody fragments (scFvs) have long been displayed on the surface of yeast and phage libraries for selection; however, the stable production of such fragments presents challenges that hamper their widespread use in diagnostics. Membrane and cell wall proteins similarly suffer from stability problems when solubilized from their native environment. Recently, cell envelope compositions that maintain membrane proteins in native or native-like lipid environment to improve their stability have been developed. This cell envelope composition approach has now been adapted toward stabilizing antibody fragments by retaining their native cell wall environment. A new class of immunoaffinity reagents has been developed that maintains antibody fragment attachment to yeast cell wall. Herein, we review recent strategies that incorporate cell wall fragments with functional scFvs, which are designed for easy production while maintaining specificity and stability when in use with simple detection platforms. These cell wall based antibody fragments are globular in structure, and heterogeneous in size, with fragments ranging from tens to hundreds of nanometers in size. These fragments appear to retain activity once immobilized onto biosensor surfaces for the specific and sensitive detection of pathogen antigens. They can be quickly and economically generated from a yeast display library and stored lyophilized, at room temperature, for up to a year with little effect on stability. This new format of scFvs provides stability, in a simple and low-cost manner toward the use of scFvs in biosensor applications. The production and \u201cpanning\u201d of such antibody cell wall composites are also extremely facile, enabling the rapid adoption of stable and inexpensive affinity reagents for emerging infectious threats.", "qid": 16, "docid": "45gdwh24", "rank": 59, "score": 6.310699939727783}, {"content": "Title: Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment Content: Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross- linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf.", "qid": 16, "docid": "9tdbygve", "rank": 60, "score": 6.29640007019043}, {"content": "Title: Structural definition of a conserved neutralization epitope on HIV-1 gp120 Content: The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 \u00c5 resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.", "qid": 16, "docid": "t1dpo0pl", "rank": 61, "score": 6.258800029754639}, {"content": "Title: 3C protein of feline coronavirus inhibits viral replication independently of the autophagy pathway Content: Abstract Feline coronavirus (FCoV) can cause either asymptomatic enteric infection or fatal peritonitis in cats. Although the mutation of FCoV accessory gene 3c has been suggested to be related to the occurrence of feline infectious peritonitis (FIP), how the 3C protein is involved in this phenomenon remains unknown. To investigate the role of the 3C protein, a full-length 3c gene was transiently expressed and the cytoplasmic distribution of the protein was found to be primarily in the perinuclear region. Using 3c-stable expression cells, the replication of a 3c-defective FCoV strain was titrated and a significant decrease in replication (p < 0.05) was observed. The mechanism underlying the decreased FIPV replication caused by the 3C protein was further investigated; neither the induction nor inhibition of autophagy rescued the viral replication. Taken together, our data suggest that the 3C protein might have a virulence-suppressing effect in FCoV-infected cats. Deletion of the 3c gene could therefore cause more efficient viral replication, which leads to a fatal infection.", "qid": 16, "docid": "qn1awvxk", "rank": 62, "score": 6.250400066375732}, {"content": "Title: Closing the loop on plastic packaging materials: What is quality and how does it affect their circularity? Content: While attention on the importance of closing materials loops for achieving circular economy (CE) is raging, the technicalities of doing so are often neglected or difficult to overcome. These technicalities determine the ability of materials, components and products (MCPs) to be properly recovered and redistributed for reuse, recycling or recovery, given their remaining functionality, described here as the remaining properties and characteristics of MCPs. The different properties of MCPs make them useful for various functions and purposes. A transition, therefore, towards a CE would require the utmost exploitation of the remaining functionality of MCPs; ideally, enabling recirculation of them back in the economy. At present, this is difficult to succeed. This short communication article explains how the remaining functionality of MCPs, defined here as quality, is perceived at different stages of the supply chain, focusing specifically on plastic packaging, and how this affects their potential recycling. It then outlines the opportunities and constraints posed by some of the interventions that are currently introduced into the plastic packaging system, aimed at improving plastic materials circularity. Finally, the article underpins the need for research that integrates systemic thinking, with technological innovations and policy reforms at all stages of the supply chain, to promote sustainable practices become established.", "qid": 16, "docid": "pmk6g515", "rank": 63, "score": 6.250199794769287}, {"content": "Title: Monolayer culture of rat parotid acinar cells without basement membrane substrates Content: Acinar cells have been difficult to maintain in primary or secondary cultures over extended periods of time. The most successful monolayer culture system reported to date requires basement membrane substrates. We report here a technique for culture of rat parotid acinar cells which does not rely upon basement membrane supports for maintenance and growth. The procedure involves gland excision, treatment to chelate metal ions, enzymatic digestion with collagenases and hyaluronidase, removal of fat and red blood cells by gravimetric separation, and nylon mesh filtration to yield a homogeneous suspension of small aggregates and single cells. The cells were examined for: a) morphology, identity, and growth; b) macromolecular synthesis; and c) secretory output. They were healthy, peroxidase positive, and growing for up to 10 d. Protein synthesis increased from the point of cell layer formation at 3 to 4 d, through 10 d, while DNA synthesis decreased. As in other studies, amylase secretion fell sharply between 2 and 4 d in culture and remained low. Although previous studies indicated that the initial isolation protocol left these acinar cells unable to thrive in monolayer culture except in the presence of basement membrane substrates, the modified technique reported herein allows these cells to attach, spread, and grow on a wide variety of commerically available plasticware. this method lends itself readily to long-term analysis of rat parotid acinar cell metabolism without the complications of dedifferentiation, cell loss through culture manipulation common in suspension cultures, or complex interactions between bioactive supports and cell surfaces.", "qid": 16, "docid": "quklubnt", "rank": 64, "score": 6.246399879455566}, {"content": "Title: Fomite transmission and disinfection strategies for SARS-CoV-2 and related viruses Content: Contaminated objects or surfaces, referred to as fomites, play a critical role in the spread of viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The long persistence of viruses (hours to days) on surfaces calls for an urgent need for surface disinfection strategies to intercept virus transmission and the spread of the disease. Elucidating the physicochemical processes and surface science underlying the adsorption and transfer of virus between surfaces, as well as their inactivation, are important in understanding how the disease is transmitted, and in developing effective interception strategies. This review aims to summarize the current knowledge and underlying physicochemical processes of virus transmission, in particular via fomites, and common disinfection approaches. Gaps in knowledge and needs for further research are also identified. The review focuses on SARS-CoV-2, but will supplement the discussions with related viruses.", "qid": 16, "docid": "xbw72k4m", "rank": 65, "score": 6.238900184631348}, {"content": "Title: Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats. Content: RATIONALE A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. OBJECTIVES We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug seeking after intravenous cocaine self-administration. METHODS Male Long-Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. RESULTS RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. CONCLUSIONS These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug seeking provides further potential for treatment by epigenetic modulation.", "qid": 16, "docid": "lwjuhfmp", "rank": 66, "score": 6.226900100708008}, {"content": "Title: Variational-LSTM Autoencoder to forecast the spread of coronavirus across the globe Content: Modelling the spread of coronavirus globally while learning trends at global and country levels remains crucial for tackling the pandemic. We introduce a novel variational LSTM-Autoencoder model to predict the spread of coronavirus for each country across the globe. This deep spatio-temporal model does not only rely on historical data of the virus spread but also includes factors related to urban characteristics represented in locational and demographic data (such as population density, urban population, and fertility rate), an index that represent the governmental measures and response amid toward mitigating the outbreak (includes 13 measures such as: 1) school closing, 2) workplace closing, 3) cancelling public events, 4) close public transport, 5) public information campaigns, 6) restrictions on internal movements, 7) international travel controls, 8) fiscal measures, 9) monetary measures, 10) emergency investment in health care, 11) investment in vaccines, 12) virus testing framework, and 13) contact tracing). In addition, the introduced method learns to generate graph to adjust the spatial dependences among different countries while forecasting the spread. We trained two models for short and long-term forecasts. The first one is trained to output one step in future with three previous timestamps of all features across the globe, whereas the second model is trained to output 10 steps in future. Overall, the trained models show high validation for forecasting the spread for each country for short and long-term forecasts, which makes the introduce method a useful tool to assist decision and policymaking for the different corners of the globe.", "qid": 16, "docid": "lrn0wpvj", "rank": 67, "score": 6.220900058746338}, {"content": "Title: Safety and feasibility of sleeve gastrectomy in morbidly obese patients following liver transplantation. Content: BACKGROUND Obesity, steroid-induced diabetes, hypercholesterolemia, and steatohepatitis can occur after liver transplantation and may respond to bariatric surgery. The safety and feasibility of bariatric surgery after liver transplantation is unknown. METHODS Nine morbidly obese patients with prior liver transplants underwent sleeve gastrectomy in a pilot program. Sleeve gastrectomy was chosen over gastric banding to avoid foreign body implantation, and over gastric bypass to maintain endoscopic access to the biliary system and reduce surgical complexity. We reviewed patient demographics, operative details, 30-day complications, weight loss, postoperative hepatic and renal functions, and resolution of comorbidities. RESULTS Sleeve gastrectomy was performed laparoscopically in eight patients and as an open procedure in one patient. The mean operative time was 165 min and mean postoperative length of stay was 5 days. Follow-up ranged from 3 to 36 months. In the first 30 days, there were three complications in three patients: mesh dehiscence after a synchronous incisional hernia repair, bile leak from the liver surface requiring laparoscopic drainage, and postoperative dysphagia that required reoperation. Calcineurin inhibitor levels and hepatic and renal functions remained stable. There were no episodes of graft rejection. At 3 months liver function tests remained stable. Excess weight loss averaged 55.5% at 6 months. CONCLUSION Sleeve gastrectomy is technically feasible after liver transplantation and resulted in weight loss without adversely affecting graft function and immunosuppression. Early complications may be more frequent as a result of adhesions of the left upper quadrant. Late complications were rare.", "qid": 16, "docid": "sb64g3ia", "rank": 68, "score": 6.212699890136719}, {"content": "Title: Liposome-Coupled Peptides Induce Long-Lived Memory CD8(+) T Cells Without CD4(+) T Cells Content: CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.", "qid": 16, "docid": "twf6g5t3", "rank": 69, "score": 6.1915998458862305}, {"content": "Title: Coronavirus envelope (E) protein remains at the site of assembly Content: Abstract Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly.", "qid": 16, "docid": "rl483cg9", "rank": 70, "score": 6.1905999183654785}, {"content": "Title: A surface plasmon resonance-based assay for small molecule inhibitors of human cyclophilin A Content: Abstract A simple protocol for generating a highly stable and active surface plasmon resonance (SPR) sensor surface of recombinant human hexahistidine cyclophilin A (His-CypA) is described. The sensor surface was sensitive and stable enough to allow, for the first time, the screening and ranking of several novel small-molecule (M r \u223c250\u2013500Da) ligands in a competition binding assay with cyclosporin A (CsA). It also allowed us to accurately determine the kinetic rate constants for the interaction between His-CypA and CsA. His-CypA was first captured on a Ni2+\u2013nitrilotriacetic acid (NTA) sensor chip and was then briefly covalently stabilized, coupling via primary amines. The significant baseline drift observed due to dissociation of weakly bound His-CypA from the Ni2+\u2013NTA moiety was eliminated, resulting in a surface that was stable for at least 36h. In addition, immobilized protein activity levels were high, typically between 85 and 95%, assayed by the interaction between His-CypA and CsA. The mean equilibrium dissociation constant for CsA (K dCsA) binding to the immobilized His-CypA was 23\u00b16nM, with on and off rates of 0.53\u00b10.1\u03bcM\u22121 s\u22121 and 1.2\u00b10.1 (\u00d710\u22122) s\u22121, respectively. These values agree well with the values for the corresponding binding constants determined from steady-state and kinetic fluorescence titrations in solution.", "qid": 16, "docid": "n76inyi8", "rank": 71, "score": 6.179999828338623}, {"content": "Title: Fuzziness endows viral motif-mimicry. Content: Motif-mimicry is exploited by viruses to interfere with host regulatory networks and has also been suggested as a prevalent strategy for eukaryotic and prokaryotic pathogens. Using the same peptide motif however does not guarantee more effective interactions with the host. Motif-mediated interactions require a flexible or disordered environment, with structural and dynamic features that should differ between the competing host and viral proteins. Using the eukaryotic linear motif (ELM) database we analyzed the protein regions which contained the eukaryotic and viral motifs, including human and human virus ELMs with common target sites. We found that although the eukaryotic motifs are associated with a lack of structure, they are more stable than their flanking regions and can serve as molecular recognition elements. In contrast, eukaryotic viral motifs are often located in more ordered regions, but have increased local flexibility or disorder compared to their embedding environment. Most viral ELMs are devoid of stable binding elements and remain fuzzy after binding. Fuzziness reduces the entropic cost of binding and imparts versatile interaction modes to increase binding promiscuity and to compete with multiple host peptides. Fuzzy interactions confer further functional benefits such as the combinatorial usage of motifs, and a fine-tuning affinity via post-translational modifications.", "qid": 16, "docid": "q01ttuo6", "rank": 72, "score": 6.173299789428711}, {"content": "Title: Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk Content: COVID19 is a devastating global pandemic with epicenters in China, Italy, Spain, and now the United States. While the majority of infected cases appear mild, in some cases, individuals present serious cardiorespiratory complications with possible long-term lung damage. Infected individuals report a range of symptoms from headaches to shortness of breath to taste and smell loss. To that end, less is known about how the virus may impact different organ systems. The SARS-CoV2 virus, which is responsible for COVID19, is highly similar to SARS-CoV. Both viruses have evolved an ability to enter host cells through direct interaction with the angiotensin converting enzyme (ACE) 2 protein at the surface of many cells. Published findings indicate that SARS-CoV can enter the human nervous system with evidence from both postmortem brains and detection in cerebrospinal fluid of infected individuals. Here, we consider the ability of SARS-CoV2 to enter and infect the human nervous system based on the strong expression of the ACE2 target throughout the brain. Moreover, we predict that nicotine exposure through various kinds of smoking (cigarettes, electronic cigarettes, or vape) can increase the risk for COVID19 neuroinfection based on known functional interactions between the nicotinic receptor and ACE2. We advocate for higher surveillance and analysis of neurocomplications in infected cases. SIGNIFICANCE STATEMENT: The COVID19 epidemic has spurred a global public health crisis. While many of the cases requiring hospitalization and intensive medical care center on cardiorespiratory treatment, a growing number of cases present neurological symptoms. Viral entry into the brain now appears a strong possibility with deleterious consequences and an urgent need for addressing.", "qid": 16, "docid": "tk8c7rh7", "rank": 73, "score": 6.170400142669678}, {"content": "Title: Unprecedented nationwide blood studies seek to track U.S. coronavirus spread Content: We still don\u2019t know how many people have been infected with the novel coronavirus, SARS-CoV-2 Not only have countries struggled to roll out wide-scale testing for the virus, those efforts inevitably will miss people who have recovered from an infection The best way to figure out how far and wide the virus has spread in a population is to look at blood Antibodies, blood proteins that the immune system produces to attack pathogens, are viral fingerprints that remain long after infections are cleared Sensitive tests can detect them even in people who never felt a single symptom of COVID-19 The World Health Organization has announced an ambitious global effort, called Solidarity II, of so-called serosurveys, studies that look for antibodies to SARS-CoV-2 in the population", "qid": 16, "docid": "na0bq2e0", "rank": 74, "score": 6.1697998046875}, {"content": "Title: The SCHOOL of nature: IV. Learning from viruses. Content: During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.", "qid": 16, "docid": "f4d6ixmj", "rank": 75, "score": 6.162899971008301}, {"content": "Title: Evaluating the evidence for direct central nervous system invasion in patients infected with the nCOVID-19 virus Content: The current nCOVID-19 pandemic is raising several questions in the approximately 25% of patients who present with neurological symptoms. While secondary brain injury from the systemic manifestations of the disease account for the majority of non-specific neurological symptoms that include headache, nausea, and progressive confusion, the question that remains unanswered is does the nCOVID-19 virus use the olfactory mucosa as a portal to directly invade the brain ? A second question is how common does direct CNS invasion complicate the classical cardiorespiratory severe form of the disease? We know from previous studies that almost all members of the Corona virus family have neurotropism. We also know from the current pandemic that deteriorating consciousness and cerebrovascular accidents are not uncommon. Several previous scattered case reports, and post-mortem examinations of brain tissue, demonstrated nCOVID-19 nucleic acid in the CSF, and brain tissue, of infected and deceased individuals. We performed a PubMed review of the literature to specifically assess the evidence for the direct CNS invasion by the nCOVID-19 virus. This phenomenon would explain the cerebral oedema and encephalitis, that does occur, and bring Neurosurgeons into the management of these patients by for example directed intra-cranial pressure management post insertion of an intra-cranial pressure monitor. Unfortunately, the answers to these questions were not definitively answered by the research reviewed. While suggestive that direct CNS invasion does occur, the exact scale and manifestations of the problem remains, to date, essentially unknown.", "qid": 16, "docid": "k2vcntfp", "rank": 76, "score": 6.144000053405762}, {"content": "Title: The utility of native MS for understanding the mechanism of action of repurposed therapeutics in COVID-19: heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor Content: The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported world-wide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-\u00e0-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.", "qid": 16, "docid": "wgfhjfiz", "rank": 77, "score": 6.1143999099731445}, {"content": "Title: Manipulation of the infectious bronchitis coronavirus genome for vaccine development and analysis of the accessory proteins() Content: Infectious bronchitis coronavirus (IBV) is the cause of the single most economically costly infectious disease of domestic fowl in the UK\u2014and probably so in many countries that have a developed poultry industry. A major reason for its continued dominance is its existence as many serotypes, determined by the surface spike protein (S), cross-protection being poor. Although controlled to some degree by live and inactivated vaccines, a new generation of IB vaccines is called for. Reverse genetic or \u2018infectious clone\u2019 systems, which allow the manipulation of the IBV genome, are key to this development. New vaccines would ideally be: genetically stable (i.e. maintain a stable attenuated phenotype); administered in ovo; and be flexible with respect to the source of the spike protein gene. Rational attenuation of IBV requires the identification of genes that are simultaneously not essential for replication and whose absence would reduce pathogenicity. Being able to modify a \u2018core\u2019 vaccine strain to make it applicable to a prevailing serotype requires a procedure for doing so, and the demonstration that \u2018spike-swapping\u2019 is sufficient to induce good immunity. We have demonstrated that four small IBV proteins, encoded by genes 3 and 5, are not essential for replication; failure to produce these proteins had little detrimental affect on the titre of virus produced. Our current molecularly cloned IBV, strain Beaudette, is non-pathogenic, so we do not know what effect the absence of these proteins would have on pathogenicity. That said, plaque size and composition of various gene 3/5 recombinant IBVs in cell culture, and reduced output and ciliostasis in tracheal organ cultures, shows that they are less aggressive than the wild-type Beaudette. Consequently these genes remain targets for rational attenuation. We have recently obtained evidence that one or more of the 15 proteins encoded by gene 1 are also determinants of pathogenicity. Hence gene 1 is also a target for rational attenuation. Replacing the S protein gene of Beaudette with that from the pathogenic M41 strain resulted in a recombinant virus that was still non-pathogenic but which did induce protection against challenge with M41. We have since made other \u2018spike-swapped\u2019 recombinants, including ones with chimaera S genes. Uniquely, our molecular clone of Beaudette is benign when administered to 18-day-old embryos, even at high doses, and induces immunity after this route of vaccination. Taken together, our results point to the creation of a new generation of IB vaccines, based on rational modification of the genome, as being a realisable objective.", "qid": 16, "docid": "urxr3xgp", "rank": 78, "score": 6.110000133514404}, {"content": "Title: On the formation of three-dimensional flows over finite-aspect-ratio wings under tip effects Content: We perform DNS of flow over finite-aspect-ratio NACA 0015 wings to characterize the tip effects on the wake dynamics. This study focuses on the development of three-dimensional separated flow over the wing, and discuss flow structures formed on the wing surface as well as in the far field wake. Vorticity is introduced into the flow in a predominantly two-dimensional manner. The vortex sheet from the wing tip rolls up around the free end to form the tip vortex. At its inception, the tip vortex is weak and its effect is spatially confined. As the flow around the tip separates, the tip effects extend farther in the spanwise direction, generating noticeable three dimensionality in the wake. For low-aspect-ratio wings, the wake remains stable due to the strong downwash over the entire span. Increasing the aspect ratio allows unsteady vortical flow to emerge away from the tip at sufficiently high angles of attack. These unsteady vortices shed and form closed vortical loops. For higher-aspect-ratio wings, the tip effects retard the near-tip shedding process, which desynchronizes from the two-dimensional shedding over the mid-span region, yielding vortex dislocation. At high angles of attack, the tip vortex exhibits noticeable undulations due to the strong interaction with the unsteady shedding vortices. The spanwise distribution of force coefficients is related to the three-dimensional wake dynamics and the tip effects. Vortical elements in the wake that are responsible for the generation of lift and drag forces are identified through the force element analysis. We note that at high angles of attack, a stationary vortical structure forms at the leading edge near the tip, giving rise to locally high lift and drag forces. The analysis performed here reveals how the vortical flow around the tip influences the separation physics, the global wake dynamics, and the spanwise force distributions.", "qid": 16, "docid": "z00bbk4p", "rank": 79, "score": 6.108399868011475}, {"content": "Title: Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus Content: The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-na\u00efve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.", "qid": 16, "docid": "c7c9ycew", "rank": 80, "score": 6.089399814605713}, {"content": "Title: Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells Content: Abstract Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum\u2013Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells.", "qid": 16, "docid": "waqyr9tq", "rank": 81, "score": 6.064899921417236}, {"content": "Title: Telepresence Mobile Robots Design and Control for Social Interaction Content: Human\u2013robot interaction has extended its application horizon to simplify how human beings interact with each other through a remotely controlled telepresence robot. The fast growth of communication technologies such as 4G and 5G has elevated the potential to establish stable audio\u2013video-data transmission. However, human\u2013robot physical interactions are still challenging regarding maneuverability, controllability, stability, drive layout, and autonomy. Hence, this paper presents a systematic design and control approach based on the customer\u2019s needs and expectations of telepresence mobile robots for social interactions. A system model and controller design are developed using the Lagrangian method and linear quadratic regulator, respectively, for different scenarios such as flat surface, inclined surface, and yaw (steering). The robot system is capable of traveling uphill (30[Formula: see text] ) and has a variable height (600\u20131200 mm). The robot is advantageous in developing countries to fill the skill gaps as well as for sharing knowledge and expertise using a virtual and mobile physical presence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12369-020-00676-3) contains supplementary material, which is available to authorized users.", "qid": 16, "docid": "mw5dctbw", "rank": 82, "score": 6.060500144958496}, {"content": "Title: A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease Content: Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3\u2032-5\u2032 exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses.", "qid": 16, "docid": "1u0cwnoq", "rank": 83, "score": 6.039400100708008}, {"content": "Title: Global trends in air travel: implications for connectivity and resilience to infectious disease threats Content: Background: Increased connectivity via air travel can facilitate the geographic spread of infectious diseases. The number of travelers alone does not explain risk; passenger origin and destination will also influence risk of disease introduction and spread. We described trends in international air passenger numbers and connectivity between countries with different capacities to detect and respond to infectious disease threats. Methods: We used the Fragile States Index (FSI) as an annual measure of country-level resilience and capacity to respond to infectious disease events. Countries are categorized as: Sustainable, Stable, Warning, or Alert, in order of increasing fragility. We included data for 177 sovereign states for the years 2007 to 2016. Annual inbound and outbound international air passengers for each country were obtained for the same time period. We examined trends in FSI score, trends in worldwide air travel, and the association between a state's FSI score and air travel. Results: Among countries included in the FSI rankings, the total number of passengers increased from 0.791 billion to 1.28 billion between 2007 and 2016. Increasing fragility was associated with a decrease in travel volumes, with a 2.9% (95% CI: 2.3-3.5%) reduction in passengers per 1-unit increase in FSI score. Overall, travel between countries of different FSI categories either increased or remained stable. The greatest increase was observed for travel to Warning countries from Warning countries, with an annual increase of 8,967,623 passengers (95%CI: 6,546,494 to 11,388,753) over the study period. Conclusions: The world's connectivity via air travel has increased dramatically over the past decade. There has been notable growth in travel from Warning and Stable countries, which comprise more than three-quarters of international air travel passengers. These countries may have suboptimal capacity to detect and respond to infectious disease threats that emerge within their borders.", "qid": 16, "docid": "1p3zelv1", "rank": 84, "score": 6.038599967956543}, {"content": "Title: Escherichia coli heat-stable enterotoxin in feces and intestines of calves with diarrhea. Content: Two experiments were conducted to evaluate detection of Escherichia coli heat-stable enterotoxin (ST) in the feces of calves as a method for implicating E coli in neonatal calf diarrhea. The first experiment evaluated the use of the infant mouse test for detection of ST in the feces of calves with naturally occurring diarrhea. Simultaneous identification of bovine enteropathogenic strains of E coli (EEC) and of other infective agents implicated in neonatal calf diarrhea was attempted in these samples. The ST was detected with certainty in only 7 of 41 samples from calves less than or equal to 3 weeks old. Enteropathogenic E coli, however, was detected in 27 samples. In 23 of these 27 samples, EEC was the only recognizable diarrheagenic agent. In a small percentage of the samples, Salmonella, rotavirus, coronavirus, and cryptosporidium were recognized alone, in combination with each other, or with EEC. In the second experiment, 6 calves were fed colostrum from cows inoculated with the bovine EEC strain B44; 6 were given colostrum from cows vaccinated with non-EEC strain 28F, and 4 were given milk from nonvaccinated heifers. Two of the calves that were given colostrum from cows inoculated with strain B44 were challenge exposed with the non-EEC strain 28F. The remaining calves were challenge exposed with the EEc strain B44. Fecal samples were taken from these calves at intervals and were examined for the presence of ST and of the challenge-exposure organism. The ST was detected in approximately one half of the fecal samples obtained, and it was most often detected in the early stages of the induced diarrhea. Calves were observed to shed the challenge-exposure EEC strain for long periods in the absence of diarrhea or detectable amounts of ST in the feces. The ST was detectable in fecal samples when the diarrhea was severe and when the dry matter content of the fecal samples was low.", "qid": 16, "docid": "1calxcf9", "rank": 85, "score": 6.036799907684326}, {"content": "Title: In vitro diagnostics of coronavirus disease 2019: technologies and application Content: Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "qid": 16, "docid": "923jpec0", "rank": 86, "score": 6.019899845123291}, {"content": "Title: In vitro diagnostics of coronavirus disease 2019: Technologies and application Content: Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "qid": 16, "docid": "r1yf75bo", "rank": 87, "score": 6.019898891448975}, {"content": "Title: Novel Coronavirus: How Atmospheric Particulate Affects Our Environment and Health Content: It is well-known that atmospheric pollution, first and foremost the particulate matter (PM), causes serious diseases in humans China\u2019s metropolises and Italy\u2019s Po Valley have in fact achieved a concerning degree of notoriety thanks to runaway air pollution problems The spread of viral respiratory diseases is facilitated in polluted environments, an example of which is the respiratory syncytial virus bronchiolitis In this opinion paper, we consider the possible relationship between air pollution, primarily airborne PM10\u20132 5, and the spread of the novel coronavirus in Northern Italy If it is true that the novel coronavirus remains active from some hours to several days on various surfaces, it is logical to postulate that the same can occur when it is adsorbed or absorbed by the atmospheric particulate matter, which may also help carry the virus into the human respiratory system As the Earth presents us with a very high bill to pay, governments and other authorities need to take prompt action to counter excessive pollution levels, both in Italy and in other countries", "qid": 16, "docid": "lnwc8mfg", "rank": 88, "score": 5.984899997711182}, {"content": "Title: Prolonged viral RNA shedding after COVID-19 symptom resolution in older convalescent plasma donors Content: Importance: The novel coronavirus, SARS-CoV-2, is responsible for a world-wide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved. Objective: To determine how long the SARS-CoV-2 remains detectable following self-reporting of viral symptom resolution. Design: A cohort of 86 previously SARS-CoV-2 positive patients were re-tested for proof of viral recovery by nasal swab and nucleic acid amplification less than 28 days after self-reported symptom resolution. Setting: A tertiary care center in a mid-size city utilizing a drive-through SAR-CoV-2 testing center. Participants: 86 previously confirmed SARS-CoV-2 positive individuals less than 28 days after self-reported resolution of symptoms evaluated as potential donors for COVID-19 convalescent plasma. Intervention: Participants underwent nasopharyngeal sampling and subsequent nucleic acid amplification for SARS-CoV-2 genes. Main Outcome: SARS-CoV-2 RNA in nasopharyngeal secretions detected by rtPCR. Results: 11/86 (13%) previously confirmed SARS-CoV-2 subjects were still positive at a median of 19 days (range 12-24 days) after symptom resolution. Older patients were more likely to be test-positive, and older positive patients had lower rtPCR CT values. Test-positive patients were not significantly different from test-negative patients with respect to days since symptom recovery. Conclusions and Resolution: These results underscore the necessity of testing COVID-19 convalescent plasma donors less than 28 days after symptom resolution and suggests that COVID-19 positive patients may need to remain in quarantine beyond the recommended two weeks following \"recovery.\"", "qid": 16, "docid": "136d42v0", "rank": 89, "score": 5.984499931335449}, {"content": "Title: Manifestations of mortality based global data of COVID-19; unifying global model through single parameter Content: Critical inspection of the world data of COVID-19 mortality rates per population number has been made and used to express extensive variations in mortality over the globe in terms of a powered parameter {lambda} varying from 0 to 1.2 expressed as a measure of strength of primary infection, originating from China source. The copying process is degenerating successively while infection is passed on to secondary subjects. We have been able to correlate global data through this parameter; any value close to or less than 1 shows significant impact of diluted multiple secondary effect. Further, the scatter diagram shows no effect of temperature of the geographical location and so is likely as the virus is only being spread from either contact or close proximity; the virus does not need to face highs and lows of temperatures of the environment. It stays only in the range of human body temperature and appears to be stable in 36 to 40C range. If it faces the environmental temperatures it is possible for its quicker deactivation but that situation never arises for this virus except when it spreads from surfaces.", "qid": 16, "docid": "wdeahrff", "rank": 90, "score": 5.976600170135498}, {"content": "Title: MagicWand: a single, designed peptide that assembles to stable, ordered alpha-helical fibers. Content: We describe a straightforward single-peptide design that self-assembles into extended and thickened nano-to-mesoscale fibers of remarkable stability and order. The basic chassis of the design is the well-understood dimeric alpha-helical coiled-coil motif. As such, the peptide has a heptad sequence repeat, abcdefg , with isoleucine and leucine residues at the a and d sites to ensure dimerization. In addition, to direct staggered assembly of peptides and to foster fibrillogenesisthat is, as opposed to blunt-ended discrete speciesthe terminal quarters of the peptide are cationic and the central half anionic with lysine and glutamate, respectively, at core-flanking e and g positions. This +,-,-,+ arrangement gives the peptide its name, MagicWand (MW). As judged by circular dichroism (CD) spectra, MW assembles to alpha-helical structures in the sub-micromolar range and above. The thermal unfolding of MW is reversible with a melting temperature >70 degrees C at 100 muM peptide concentration. Negative-stain transmission electron microscopy (TEM) of MW assemblies reveals stiff, straight, fibrous rods that extended for tens of microns. Moreover, different stains highlight considerable order both perpendicular and parallel to the fiber long axis. The dimensions of these features are consistent with bundles of long, straight coiled alpha-helical coiled coils with their axes aligned parallel to the long axis of the fibers. The fiber thickening indicates inter-coiled-coil interactions. Mutagenesis of the outer surface of the peptide i.e., at the b and f positionscombined with stability and microscopy measurements, highlights the role of electrostatic and cation-pi interactions in driving fiber formation, stability and thickening. These findings are discussed in the context of the growing number of self-assembling peptide-based fibrous systems.", "qid": 16, "docid": "r6vtzf3m", "rank": 91, "score": 5.974299907684326}, {"content": "Title: Desynchronization and Wave Pattern Formation in MPI-Parallel and Hybrid Memory-Bound Programs Content: Analytic, first-principles performance modeling of distributed-memory parallel codes is notoriously imprecise. Even for applications with extremely regular and homogeneous compute-communicate phases, simply adding communication time to computation time does often not yield a satisfactory prediction of parallel runtime due to deviations from the expected simple lockstep pattern caused by system noise, variations in communication time, and inherent load imbalance. In this paper, we highlight the specific cases of provoked and spontaneous desynchronization of memory-bound, bulk-synchronous pure MPI and hybrid MPI+OpenMP programs. Using simple microbenchmarks we observe that although desynchronization can introduce increased waiting time per process, it does not necessarily cause lower resource utilization but can lead to an increase in available bandwidth per core. In case of significant communication overhead, even natural noise can shove the system into a state of automatic overlap of communication and computation, improving the overall time to solution. The saturation point, i.e., the number of processes per memory domain required to achieve full memory bandwidth, is pivotal in the dynamics of this process and the emerging stable wave pattern. We also demonstrate how hybrid MPI-OpenMP programming can prevent desirable desynchronization by eliminating the bandwidth bottleneck among processes. A Chebyshev filter diagonalization application is used to demonstrate some of the observed effects in a realistic setting.", "qid": 16, "docid": "pgkgfrwx", "rank": 92, "score": 5.972499847412109}, {"content": "Title: Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure. Content: Inhaled nitric oxide (INO) is a colorless, odorless gas that is also a potent pulmonary vasodilator. When given via the inhaled route it is a selective pulmonary vasodilator. INO is approved by the United States Food and Drug Administration (FDA) for the treatment of term and near-term neonates with hypoxemic respiratory failure associated with clinical or echocardiographic evidence of pulmonary arterial hypertension. A systematic review of the literature was conducted with the intention of making recommendations related to the clinical use of INO for its FDA-approved indication. Specifically, we wrote these evidence-based clinical practice guidelines to address the following questions: (1) What is the evidence for labeled use? (2) What are the specific indications for INO for neonates with acute hypoxemic respiratory failure? (3) Does the use of INO impact oxygenation, mortality, or utilization of extracorporeal membrane oxygenation (ECMO)? (4) Does INO affect long-term outcomes? (5) Is INO cost-effective therapy? (6) How is the appropriate dosing regimen and dose response to INO established? (7) How is the dose of INO titrated and weaned? (8) Which INO delivery system should be used? (9) How should INO be implemented with different respiratory support devices? (10) What adverse effects of INO should be monitored, and at what frequency? (11) What physiologic parameters should be monitored during INO? (12) Is scavenging of gases necessary to protect the caregivers? Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring system, 22 recommendations are developed for the use of INO in newborns.", "qid": 16, "docid": "ti3nytq3", "rank": 93, "score": 5.965000152587891}, {"content": "Title: Effects of temperature on COVID-19 transmission Content: Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.", "qid": 16, "docid": "ycrrsr5c", "rank": 94, "score": 5.964099884033203}, {"content": "Title: Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials Content: The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.", "qid": 16, "docid": "4d4l6mzl", "rank": 95, "score": 5.963799953460693}, {"content": "Title: Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine Content: Abstract Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of \u223c10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.", "qid": 16, "docid": "w9rqnz9h", "rank": 96, "score": 5.963099956512451}, {"content": "Title: Sialic acids as receptor determinants for coronaviruses Content: Among coronaviruses, several members are able to interact with sialic acids. For bovine coronavirus (BCoV) and related viruses, binding to cell surface components containing N-acetyl-9- O-acetylneuraminic acid is essential for initiation of an infection. These viruses resemble influenza C viruses because they share not only the receptor determinant, but also the presence of an acetylesterase that releases the 9- O-acetyl group from sialic acid and thus abolishes the ability of the respective sialoglycoconjugate to function as a receptor for BCoV. As in the case of influenza viruses, the receptor-destroying enzyme of BCoV is believed to facilitate the spread of virus infection by removing receptor determinants from the surface of infected cells and by preventing the formation of virus aggregates. Another coronavirus, porcine transmissible gastroenteritis virus (TGEV) preferentially recognizes N-glycolylneuraminic acid. TGEV does not contain a receptor-destroying enzyme and does not depend on the sialic acid binding activity for infection of cultured cells. However, binding to sialic acids is required for the enteropathogenicity of TGEV. Interaction with sialoglycoconjugates may help the virus to pass through the sialic acid-rich mucus layer that covers the viral target cells in the epithelium of the small intestine. We discuss that the BCoV group of viruses may have evolved from a TGEV-like ancestor by acquiring an acetylesterase gene through heterologous recombination.", "qid": 16, "docid": "2i5paxb6", "rank": 97, "score": 5.960400104522705}, {"content": "Title: On the role of governmental action and individual reaction on COVID-19 dynamics in South Africa: A mathematical modelling study Content: Mathematical models proffer a rational basis to epidemiologists and policy makers on how, where and when to control an infectious disease. Through mathematical models one can explore and provide solutions to phenomena which are difficult to measure in the field. In this paper, a mathematical models has been used to explore the role of government and individuals reaction to the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The proposed framework incorporates all the relevant biological factors as well as the effects of individual behavioral reaction and government action such as travel restrictions, social distancing, hospitalization, quarantine and hygiene measures. Understanding the dynamics of this highly contagious SARS-CoV-2, which at present does not have any therapy assist the policy makers on evaluating the effectiveness of the control measures currently being implemented. Moreover, policy makers can have insights on short-and-long term dynamics of the disease. The proposed conceptual framework was combined with data on cases of coronavirus disease (COVID-19) in South Africa, March 2020 to early May 2020. Overall, our work demonstrated optimal conditions necessary for the infection to die out as well as persist.", "qid": 16, "docid": "v5bmsln8", "rank": 98, "score": 5.957799911499023}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management Content: As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.", "qid": 16, "docid": "q82gkygd", "rank": 99, "score": 5.957300186157227}, {"content": "Title: Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation. Content: Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding \"lectin\" domain appended to a receptor-destroying sialate-O-acetylesterase (\"esterase\"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein-carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins \"see\" sugars and how this affects protein and virus evolution.", "qid": 16, "docid": "eu3ohrrp", "rank": 100, "score": 5.953800201416016}]}
{"query": "are there any clinical trials available for the coronavirus", "hits": [{"content": "Title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Content: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.", "qid": 17, "docid": "iymmf4k6", "rank": 1, "score": 7.723899841308594}, {"content": "Title: IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? Content: At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF\u03b1), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be \u2018life-saving\u2019 as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.", "qid": 17, "docid": "s5lailkp", "rank": 2, "score": 7.560100078582764}, {"content": "Title: IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? Content: At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF&#945;), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be 'life-saving' as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.", "qid": 17, "docid": "z91sksce", "rank": 3, "score": 7.560099124908447}, {"content": "Title: Drug Repurposing to find Inhibitors of SARS-CoV-2 Main Protease Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. Currently there is no known vaccine or specific antiviral treatment for COVID-19 and so, there is an urgent need for expedite discovery of new therapeutics to combat the disease until a vaccine will be available worldwide. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage (over conventional approaches that attempt to develop a drug from scratch) that time frame of the overall process can be significantly reduced because of the few number of clinical trial required. In this work, a virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. As a result of this study, 12 drugs are proposed as candidates for inhibitors of the Mpro enzyme. Some of the selected compounds are antiviral drugs that are already being tested in COVID-19 clinical trials (i.e. ribavirin) or are used to alleviate symptoms of the disease (i.e. codeine). Surprisingly, the most promising candidate is the naturally occurring broad spectrum antibiotic oxytetracycline. This compound has largely outperformed the remaining selected candidates along all filtering steps of our virtual screening protocol. If the activity of any of these drugs is experimentally corroborated, they could be used directly in clinical trials without the need for pre-clinical testing or safety evaluation since they are already used as drugs for other diseases.", "qid": 17, "docid": "z17knvts", "rank": 4, "score": 7.3765997886657715}, {"content": "Title: Missing clinical trial data: the knowledge gap in the safety of potential COVID-19 drugs Content: Abstract (290/300 words) Objectives: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the knowledge gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19. Design: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched using the NCT number to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. Results: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. 1172 (31.2%) completed trials had tabular results on ClinicalTrials.gov. A further 1066 (28.4%) completed trials had results from the literature search, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). Conclusion: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause a large burden of additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.", "qid": 17, "docid": "m938suxh", "rank": 5, "score": 7.375100135803223}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 17, "docid": "98zpr960", "rank": 6, "score": 7.170199871063232}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution. Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 17, "docid": "opbozg55", "rank": 7, "score": 7.170198917388916}, {"content": "Title: Interventions for treatment of COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING Project) Content: BACKGROUND: COVID-19 is a rapidly spreading virus infection that has quickly caused extensive burden to individual, families, countries, and the globe. No intervention has yet been proven effective for the treatment of COVID-19. Some randomized clinical trials assessing the effects of different drugs have been published, and more are currently underway. There is an urgent need for a living, dynamic systematic review that continuously evaluates the beneficial and harmful effects of all available interventions for COVID-19. METHODS/DESIGN: We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and perform risk of bias assessment. We will include randomized clinical trials comparing any intervention for the treatment of COVID-19 (e.g., pharmacological interventions, fluid therapy, invasive or noninvasive ventilation, or similar interventions) with any comparator (e.g., an \"active\" comparator, standard care, placebo, no intervention, or \"active placebo\") for participants in all age groups with a diagnosis of COVID-19. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analysis, and individual patient data meta-analyses. Risk of bias will be assessed with domains, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DISCUSSION: COVID-19 has become a pandemic with substantial mortality. A living systematic review evaluating the beneficial and harmful effects of pharmacological and other interventions is urgently needed. This review will continuously inform best practice in treatment and clinical research of this highly prevalent disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178787.", "qid": 17, "docid": "x1jg0083", "rank": 8, "score": 7.070000171661377}, {"content": "Title: Interventions for treatment of COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING Project) Content: BACKGROUND: COVID-19 is a rapidly spreading virus infection that has quickly caused extensive burden to individual, families, countries, and the globe. No intervention has yet been proven effective for the treatment of COVID-19. Some randomized clinical trials assessing the effects of different drugs have been published, and more are currently underway. There is an urgent need for a living, dynamic systematic review that continuously evaluates the beneficial and harmful effects of all available interventions for COVID-19. METHODS/DESIGN: We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and perform risk of bias assessment. We will include randomized clinical trials comparing any intervention for the treatment of COVID-19 (e.g., pharmacological interventions, fluid therapy, invasive or noninvasive ventilation, or similar interventions) with any comparator (e.g., an \u201cactive\u201d comparator, standard care, placebo, no intervention, or \u201cactive placebo\u201d) for participants in all age groups with a diagnosis of COVID-19. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analysis, and individual patient data meta-analyses. Risk of bias will be assessed with domains, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DISCUSSION: COVID-19 has become a pandemic with substantial mortality. A living systematic review evaluating the beneficial and harmful effects of pharmacological and other interventions is urgently needed. This review will continuously inform best practice in treatment and clinical research of this highly prevalent disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178787", "qid": 17, "docid": "xc5jrjnl", "rank": 9, "score": 7.0699992179870605}, {"content": "Title: Current State of Research About Chinese Herbal Medicines (CHM) for the Treatment of Coronavirus Disease 2019 (COVID-19): A Scoping Review. Content: Background: There is currently no effective treatment against coronavirus disease 2019 (COVID-19). The optimal selection of interventions targeting the virus is unknown. Therefore, evidence from randomized controlled trials (RCTs) to support specific treatment against COVID-19 is urgently needed. The use of Chinese herbal medicines (CHMs) might have a role in the treatment and symptomatic management of patients with COVID-19. It was aimed at providing an overview of the available evidence and ongoing trials concerning the effects of CHMs for the treatment of COVID-19. Methods: This is a narrative review of relevant studies. Searches were conducted to identify documents published till April 22, 2020. Electronic databases, evidence-based collections, websites of relevant organizations, and trial registries were consulted. Results: A total of 25 guidelines on the treatment of patients with COVID-19 were identified. Four guidelines provided recommendations on the use of CHMs; these guidelines were developed in China and South Korea and were based on the consensus of experts exclusively. The remaining 21 guidelines provided no guidance on CHMs. No finished RCTs of CHMs for the treatment of patients with COVID-19 was found. According to the evidence evaluated in this review, a Cochrane review of CHMs for severe acute respiratory syndrome and five uncontrolled observational studies of the effects of CHMs in patients with COVID-19, the effects of CHMs for COVID-19 are unknown. A total of 52 ongoing clinical trials of CHM interventions for the treatment of COVID-19 were found. These trials will be carried out mostly in China (n = 51). Forty (77%) of the ongoing trials will be randomized, whereas 12 (23%) have an unclear sequence generation procedure. Forty-seven trials (90%) will have a sample size <400 participants. Conclusions: To the authors' knowledge, only the Chinese and the South Korean guidelines recommend CHMs as a treatment option for patients with COVID-19. These guidelines base their recommendations on the consensus of experts. Clinical guidelines or health authorities from other countries do not provide advice on CHMs. Due to the absence of RCT, there is currently no reliable evidence on the effects of any specific CHM intervention for the treatment of patients with COVID-19. A high number of clinical trials of different herbal products are being currently conducted in China.", "qid": 17, "docid": "3esrmf0x", "rank": 10, "score": 7.007199764251709}, {"content": "Title: Current State of Research About Chinese Herbal Medicines (CHM) for the Treatment of Coronavirus Disease 2019 (COVID-19): A Scoping Review Content: Background: There is currently no effective treatment against coronavirus disease 2019 (COVID-19). The optimal selection of interventions targeting the virus is unknown. Therefore, evidence from randomized controlled trials (RCTs) to support specific treatment against COVID-19 is urgently needed. The use of Chinese herbal medicines (CHMs) might have a role in the treatment and symptomatic management of patients with COVID-19. It was aimed at providing an overview of the available evidence and ongoing trials concerning the effects of CHMs for the treatment of COVID-19. Methods: This is a narrative review of relevant studies. Searches were conducted to identify documents published till April 22, 2020. Electronic databases, evidence-based collections, websites of relevant organizations, and trial registries were consulted. Results: A total of 25 guidelines on the treatment of patients with COVID-19 were identified. Four guidelines provided recommendations on the use of CHMs; these guidelines were developed in China and South Korea and were based on the consensus of experts exclusively. The remaining 21 guidelines provided no guidance on CHMs. No finished RCTs of CHMs for the treatment of patients with COVID-19 was found. According to the evidence evaluated in this review, a Cochrane review of CHMs for severe acute respiratory syndrome and five uncontrolled observational studies of the effects of CHMs in patients with COVID-19, the effects of CHMs for COVID-19 are unknown. A total of 52 ongoing clinical trials of CHM interventions for the treatment of COVID-19 were found. These trials will be carried out mostly in China (n = 51). Forty (77%) of the ongoing trials will be randomized, whereas 12 (23%) have an unclear sequence generation procedure. Forty-seven trials (90%) will have a sample size <400 participants. Conclusions: To the authors' knowledge, only the Chinese and the South Korean guidelines recommend CHMs as a treatment option for patients with COVID-19. These guidelines base their recommendations on the consensus of experts. Clinical guidelines or health authorities from other countries do not provide advice on CHMs. Due to the absence of RCT, there is currently no reliable evidence on the effects of any specific CHM intervention for the treatment of patients with COVID-19. A high number of clinical trials of different herbal products are being currently conducted in China.", "qid": 17, "docid": "rssq2v7k", "rank": 11, "score": 7.007198810577393}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \"Remdesivir\" or 'GS-5734\u00e2\u0080\u00b3 AND \"COVID-19\" or \"SARS-CoV-2\" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 17, "docid": "1eiw7bxh", "rank": 12, "score": 6.970399856567383}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \u201cRemdesivir\u201d or \u2018GS-5734\u2033 AND \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 17, "docid": "gqqdx2r5", "rank": 13, "score": 6.970398902893066}, {"content": "Title: Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic? Content: CONTEXT: Coronavirus disease 2019 (COVID-19) pandemic has caused increased interest in the application of telehealth to provide care without exposing patients and physicians to the risk of contagion. The urological literature on the topic is sparse. OBJECTIVE: To perform a systematic review of the literature and evaluate all the available studies on urological applications of telehealth. EVIDENCE ACQUISITION: After registration on PROSPERO, we searched PubMed and Scopus databases to collect any kind of studies evaluating any telehealth interventions in any urological conditions. The National Toxicology Program/Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies was used to estimate the risk of bias. A narrative synthesis was performed. EVIDENCE SYNTHESIS: We identified 45 studies (11 concerning prostate cancer [PCa], three hematuria management, six urinary stones, 14 urinary incontinence [UI], five urinary tract infections [UTIs], and six other conditions), including 12 randomized controlled trials. The available literature indicates that telemedicine has been implemented successfully in several common clinical scenarios, including the decision-making process following a diagnosis of nonmetastatic PCa, follow-up care of patients with localized PCa after curative treatments, initial diagnosis of hematuria, management diagnosis and follow-up care of uncomplicated urinary stones and uncomplicated UTIs, and initial evaluation, behavioral therapies, and pelvic floor muscle training in UI patients, as well as follow-up care after surgical treatments of stress urinary incontinence or pelvic organ prolapse. The methodological quality of most of the reports was good. CONCLUSIONS: Telehealth has been implemented successfully in selected patients with PCa, UI, pelvic organ prolapse, uncomplicated urinary stones, and UTIs. Many urological conditions are suitable for telehealth, but more studies are needed on other highly prevalent urological malignant and benign conditions. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine. More robust data on long-term efficacy, safety, and health economics are necessary. PATIENT SUMMARY: The diffusion of coronavirus disease 2019 (COVID-19) infections has recently increased the interest in telehealth, which is the adoption of telecommunication to deliver any health care activity. The available literature indicates that telemedicine has been adopted successfully in selected patients with several common clinical urological conditions, including prostate cancer, uncomplicated urinary stones, uncomplicated urinary infections, urinary incontinence, or pelvic organ prolapse. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine, but more robust data on long-term efficacy, safety, and costs are necessary.", "qid": 17, "docid": "hd1j0nud", "rank": 14, "score": 6.939599990844727}, {"content": "Title: Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic? Content: Abstract Context Coronavirus disease 2019 (COVID-19) pandemic has caused increased interest in the application of telehealth to provide care without exposing patients and physicians to the risk of contagion. The urological literature on the topic is sparse. Objective To perform a systematic review of the literature and evaluate all the available studies on urological applications of telehealth. Evidence acquisition After registration on PROSPERO, we searched PubMed and Scopus databases to collect any kind of studies evaluating any telehealth interventions in any urological conditions. The National Toxicology Program/Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies was used to estimate the risk of bias. A narrative synthesis was performed. Evidence synthesis We identified 45 studies (11 concerning prostate cancer [PCa], three hematuria management, six urinary stones, 14 urinary incontinence [UI], five urinary tract infections [UTIs], and six other conditions), including 12 randomized controlled trials. The available literature indicates that telemedicine has been implemented successfully in several common clinical scenarios, including the decision-making process following a diagnosis of nonmetastatic PCa, follow-up care of patients with localized PCa after curative treatments, initial diagnosis of hematuria, management diagnosis and follow-up care of uncomplicated urinary stones and uncomplicated UTIs, and initial evaluation, behavioral therapies, and pelvic floor muscle training in UI patients, as well as follow-up care after surgical treatments of stress urinary incontinence or pelvic organ prolapse. The methodological quality of most of the reports was good. Conclusions Telehealth has been implemented successfully in selected patients with PCa, UI, pelvic organ prolapse, uncomplicated urinary stones, and UTIs. Many urological conditions are suitable for telehealth, but more studies are needed on other highly prevalent urological malignant and benign conditions. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine. More robust data on long-term efficacy, safety, and health economics are necessary. Patient summary The diffusion of coronavirus disease 2019 (COVID-19) infections has recently increased the interest in telehealth, which is the adoption of telecommunication to deliver any health care activity. The available literature indicates that telemedicine has been adopted successfully in selected patients with several common clinical urological conditions, including prostate cancer, uncomplicated urinary stones, uncomplicated urinary infections, urinary incontinence, or pelvic organ prolapse. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine, but more robust data on long-term efficacy, safety, and costs are necessary.", "qid": 17, "docid": "rseu9nce", "rank": 15, "score": 6.93959903717041}, {"content": "Title: Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences. Content: The rapid progression of corona virus disease in 2019 (COVID-19) pandemic has become an unprecedented global concern. This systemic review aimed at evaluating the available evidence on efficacy, safety to identify any promising role for compassionate use of remdesivir in patient suffered for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE, Cochrane Library for randomized controlled trials (RCTs), prospective case series studies and case reports that evaluated use of remdesivir in COVID-19. The outcomes were mortality, recovery rate, length of hospital stay and clinical outcome. Though the drug remdesivir (RDV) is not approved by the FDA, still the \"Emergency Use Authorization\" (EUA) for compassionate use in severe cases is endorsed. After vigorous searching, screening and sorting of completed and published scientific evidences in electronic database, there were only 2 randomized control trial (RCT), 2 uncontrolled trials found until April 2020. We also included 3 published case reports to analyze the validity use of RDV because of the scarcity of evidence based reports. Remdesivir was thought to be one of the promising options for treating the patients of COVID-19 based on few laboratory experiments and reports from some compassionate use and case reports. The safety and efficacy of this drug in COVID-19 cases require high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.", "qid": 17, "docid": "x89iy0m2", "rank": 16, "score": 6.912499904632568}, {"content": "Title: Clinical evidence for repurposing chloroquine and hydroxychloroquine as antiviral agents: a systematic review Content: BACKGROUND: Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with new viral epidemics. OBJECTIVES: To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection. DATA SOURCES: PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions. Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015. MedRxiv for pre-prints within the last 12 months. STUDY ELIGIBILITY CRITERIA: Interventional and prospective observational studies (with or without a control group) PARTICIPANTS: Adults and children with a confirmed viral infection. INTERVENTION: Use of chloroquine or hydroxychloroquine as antiviral agents in one or more groups of the study. METHODS: Two authors independently screened abstracts and all authors agreed on eligible studies. A meta-analysis was planned if similar studies were available in terms of participants, intervention, comparator and outcomes. RESULTS: Nineteen studies were eligible (HIV: 8, HCV: 2, Dengue: 2, Chikungunya: 1, COVID-19: 6) including two pre-prints. Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV is inconsistent. CQ is ineffective in curing dengue (high certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure if CQ or HCQ has any benefit in clearing viraemia (very low certainty evidence). CONCLUSIONS: Using HCQ or CQ for HIV/HCV infections is clinically irrelevant now as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue and the same conclusion is likely for chikungunya infection. More evidence is needed to confirm if HCQ or CQ is beneficial in COVID-19 infection.", "qid": 17, "docid": "1q9bhwpb", "rank": 17, "score": 6.908199787139893}, {"content": "Title: Current Evidence of the Pharmacological Treatments for Novel Coronavirus Disease 2019 (COVID-19) A Scoping Review Content: Background: As of May 2 2020, 3,267,184 confirmed cases of COVID-19 and 229,971 COVID-19-caused deaths have been reported worldwide. Currently, there is limited clarity on the pharmacological treatments available for the novel coronavirus. We systematically identified the current evidence and ongoing research on the pharmacological treatments for COVID-19. Methods: We conducted a scoping review using PRISMA-ScR. Observational studies, including cohort studies and case series, as well as experimental studies, including randomized controlled trials (RCTs) and non-RCTs were searched electronically on April 7, 2020 and by hand on May 1, 2020. PubMed, EMBASE, and Cochrane library databases were searched along with seven trial registries. The inclusion criteria were patients with confirmed COVID-19 who received pharmacological therapies, including hydroxychloroquine and chloroquine, lopinavir/ritonavir, remdesivir, tocilizumab, and favipiravir. Results: We identified 222 studies on pharmacological treatment of the novel coronavirus. We included 11 of these studies in this review, including the ones on hydroxychloroquine and chloroquine (one cohort), lopinavir/ritonavir (one RCT, three cohorts, and two case series), remdesivir (one RCT and one case series), tocilizumab (one case series), and favipiravir (one RCT). In the three RCTs carried out in China, both lopinavir/ritonavir and remdesivir did not show any significant earlier clinical improvement in case of severe infection [Hazard ratio (HR): 1.31, p=0.09 and HR: 1.24, p=0.24, respectively], The clinical recovery rate on day seven was not significantly different between the favipiravir and arbidol groups (p=0.14) for moderate patients, although the duration of pyrexia and cough in the favipiravir group was significantly shorter as compared to the arbidol group (p<0.01). There are 135 ongoing RCTs, including 72 for hydroxychloroquine and chloroquine, 29 for lopinavir/ritonavir, 14 for remdesivir, 16 for tocilizumab, and 4 for favipiravir. Conclusion: The clinical effectiveness and safety of these drugs for the treatment of COVID-19 remains unclear owing to the lack of large, high-quality RCTs. However, in the event of emerging infectious diseases, we need to repeatedly and systematically update the best available evidence to avoid misleading information.", "qid": 17, "docid": "txvx5fy5", "rank": 18, "score": 6.905099868774414}, {"content": "Title: Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19 Content: BACKGROUND: Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (C(max)), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC(50)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (C(max): EC(50)roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production. METHODS: A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5\u201314 days in participants experiencing acute infections of any kind. Data extracted were grade 1\u20134 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects. Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries. RESULTS: Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited. Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100 mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day. CONCLUSION: Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500 mg BD, up to $4.08 at 1100 mg TDS. Further trials in COVID-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic.", "qid": 17, "docid": "1wr7oud8", "rank": 19, "score": 6.889100074768066}, {"content": "Title: Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19. Content: Background Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (Cmax), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC50) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Cmax : EC50 roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production. Methods A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5-14 days in participants experiencing acute infections of any kind. Data extracted were grade 1-4 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects.Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries. Results Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited.Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100 mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day. Conclusion Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500 mg BD, up to $4.08 at 1100 mg TDS. Further trials in COVID-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic.", "qid": 17, "docid": "6enxm9l5", "rank": 20, "score": 6.88909912109375}, {"content": "Title: Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19 Content: Background: Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19) One drug that has shown promising results in vitro is nitazoxanide Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (Cmax), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC50) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Cmax : EC50 roughly equal to 14:1) As such, it is important to investigate the safety of nitazoxanide for further trials Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production Methods: A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials gov We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5-14 days in participants experiencing acute infections of any kind Data extracted were grade 1-4 and serious adverse events (AEs) Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered Our estimated costs were compared with publicly available list prices from a selection of countries Results: Nine RCTs of nitazoxanide were identified for inclusion These RCTs accounted for 1514 participants and an estimated 95 3 person-years-of-follow-up No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials Mild GI AEs increased with dose No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported There were no teratogenic concerns, but the evidence base was very limited Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1 41 The daily cost would therefore be $0 10 The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh At a higher dose of 1100 mg TDS, our estimated cost was $4 08 per 14-day course, equivalent to $0 29 per day Conclusion: Nitazoxanide demonstrates a good safety profile at approved doses However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity We estimate that it would be possible to manufacture nitazoxanide as generic for $1 41 for a 14-day treatment course at 500 mg BD, up to $4 08 at 1100 mg TDS Further trials in COVID-19 patients should be initiated If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic", "qid": 17, "docid": "cjml56d2", "rank": 21, "score": 6.889098167419434}, {"content": "Title: Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19 Content: BACKGROUND: Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (C(max)), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC(50)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (C(max ): EC(50 )roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production. METHODS: A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5\u201314 days in participants experiencing acute infections of any kind. Data extracted were grade 1\u20134 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects. Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries. RESULTS: Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited. Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100 mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day. CONCLUSION: Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500 mg BD, up to $4.08 at 1100 mg TDS. Further trials in COVID-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic.", "qid": 17, "docid": "qvcbfnbf", "rank": 22, "score": 6.889097213745117}, {"content": "Title: Medication for COVID-19-an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with Clinical- Trials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARSCoV- 2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 17, "docid": "jd1b7asr", "rank": 23, "score": 6.828199863433838}, {"content": "Title: Clinical evidence for repurposing chloroquine and hydroxychloroquine as antiviral agents: a systematic review Content: BACKGROUND: Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics. AIMS: To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection. SOURCES: PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions; Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015; MedRxiv for preprints within the last 12 months. CONTENT: Study eligibility criteria were interventional and prospective observational studies (with or without a control group). Participants were adults and children with a confirmed viral infection. Interventions included the use of CQ or HCQ as antiviral agent in one or more groups of the study. Two authors independently screened abstracts, and all authors agreed on eligible studies. A meta-analysis was planned if studies were available which were similar in terms of participants, intervention, comparator and outcomes. Nineteen studies (including two preprints) were eligible (HIV 8, HCV 2, dengue 2, chikungunya 1, COVID-19 6). Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV are inconsistent. CQ is ineffective in curing dengue (high-certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure whether either CQ or HCQ has any benefit in clearing viraemia (very-low-certainty evidence). IMPLICATIONS: Using HCQ or CQ for HIV/HCV infections is now clinically irrelevant as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue, and the same conclusion is likely for chikungunya. More evidence is needed to confirm whether either HCQ or CQ is beneficial in COVID-19 infection.", "qid": 17, "docid": "e12v80n1", "rank": 24, "score": 6.823400020599365}, {"content": "Title: Medication for COVID-19\u2014an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with ClinicalTrials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARS-CoV-2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 17, "docid": "vyeescn8", "rank": 25, "score": 6.77209997177124}, {"content": "Title: Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure Content: Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.", "qid": 17, "docid": "vqxrjtgb", "rank": 26, "score": 6.764500141143799}, {"content": "Title: Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia? Content: Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.", "qid": 17, "docid": "o04up4dr", "rank": 27, "score": 6.747399806976318}, {"content": "Title: Human Coronavirus Data from Four Clinical Trials of Masks and Respirators Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 17, "docid": "gey0nidn", "rank": 28, "score": 6.652900218963623}, {"content": "Title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 17, "docid": "vjg2auh7", "rank": 29, "score": 6.652899265289307}, {"content": "Title: Long-Term Care Facilities: A Cornucopia of Viral Pathogens Content: OBJECTIVES: To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. DESIGN: Observational. SETTING: Thirty-three Boston-area LTCFs over a 3-year period. PARTICIPANTS: Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. MEASUREMENTS: Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. RESULTS: A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P = .007), pneumonia (P = .02), and any lower respiratory tract infection (P = .002) was significantly associated with having a viral diagnosis. CONCLUSION: A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations.", "qid": 17, "docid": "54f67o77", "rank": 30, "score": 6.648600101470947}, {"content": "Title: Clinical trials on drug repositioning for COVID-19 treatment Content: The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants\u2019 clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.", "qid": 17, "docid": "vxqdfiel", "rank": 31, "score": 6.545599937438965}, {"content": "Title: Systematic review of reporting benefits and harms of surgical interventions in randomized clinical trials. Content: BACKGROUND Standardized reporting methods facilitate comparisons between studies. Reporting of data on benefits and harms of treatments in surgical RCTs should support clinical decision-making. Correct and complete reporting of the outcomes of clinical trials is mandatory to appreciate available evidence and to inform patients properly before asking informed consent. METHODS RCTs published between January 2005 and January 2017 in 15 leading journals comparing a surgical treatment with any other treatment were reviewed systematically. The CONSORT checklist, including the extension for harms, was used to appraise the publications. Beneficial and harmful treatment outcomes, their definitions and their precision measures were extracted. RESULTS Of 1200 RCTs screened, 88 trials were included. For the differences in effect size of beneficial outcomes, 68 per cent of the trials reported a P value only but not a 95 per cent confidence interval. For harmful effects, this was 67 per cent. Only five of the 88 trials (6 per cent) reported a number needed to treat, and no study a number needed to harm. Only 61 per cent of the trials reported on both the beneficial and harmful outcomes of the intervention studied in the same paper. CONCLUSION Despite CONSORT guidelines, current reporting of benefits and harms in surgical trials does not facilitate clear communication of treatment outcomes with patients. Researchers, reviewers and journal editors should ensure proper reporting of treatment benefits and harms in trials.", "qid": 17, "docid": "9avz4c51", "rank": 32, "score": 6.542699813842773}, {"content": "Title: Mechanistic rationale of drugs, Primary endpoints, Geographical distribution of clinical trials against Severe acute respiratory syndrome-related coronavirus-2: A Systematic Review Content: Objective To do a systematic review and critical appraisal of the ongoing clinical trials that are assessing various therapeutic interventions against SARS-CoV-2 with an aim to provide insight into the various interventions tested, clinical rationale, geographical distribution of the trials as well as the endpoints assessed in the studies. Design Rapid systematic review and critical appraisal of the ongoing clinical trials against SARS-CoV-2. Data sources ClinicalTrials.gov, World health organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Cochrane COVID registry were assessed till May 11th 2020. Study selection Studies on any intervention based randomized controlled trials (RCTs), prospective clinical studies on SARS-CoV-2 in patients [\u2265]18 years of age. Studies on autopsy series, preclinical studies, diagnostic methods, mathematical modelling, epidemiology and health services research, pediatric populations were excluded. Data extraction The data was extracted by two authors independently into pre-defined forms based on the SPIRIT 2013 checklist. The data was extracted on various domains such as trial number, study title, abstract of the study, interventions assessed, sample size, phase of the study, study sponsor, primary endpoint assessed and country of study. Results The search resulted in 3242 ongoing studies of which 829 studies were included. There are 134 different drug-based interventions being assessed in 463 clinical trials as treatment options. Seventy-two studies assessed preventive options of which 53 are drug-based prophylaxis and 19 assessed vaccines. Herbal medicines are being assessed in 79 studies; convalescent plasma therapy in 56 studies; stem cell based interventions in 42 studies; anesthesia-based interventions in 31 studies, machine-based interventions in 24 studies, mental health- based interventions in18 studies, rehabilitation based interventions in 12 studies and miscellaneous interventions in 32 studies. China accounts for 35% of all ongoing clinical studies followed by USA 23%, France 7%, Spain 3.3%,Canada 2%, multi-country studies account only for 1.5% (13) and other countries together account for 28%.Amongst the 463 studies assessing drug-based treatment options, studies that are funded by federal and academic institutions are 79.6%, pharmaceutical company funded studies are 15.11% and no funding information is available in 5.10%. The definitive outcomes like mortality are being assessed as primary outcome in 22.8% of the studies only and need for ventilator in 6.2% of the studies. Rest of the studies has primary outcomes such as clinical recovery (15.9%), viral clearance(17.4%), time to recovery (10.1%), oxygen improvement (5.6%), ICU admission (1.9%), lab and imaging(6.4%), adverse effects (5.3%) and symptom reduction(1.5%),no outcome reported(6.2%) which account for 71% of the studies. Amongst the pharmaceutical company funded drug-based studies, only 20% of the studies had mortality as the primary outcome. Only 5.5% of the ongoing clinical trials are specifically designed to assess the most vulnerable population like elderly, patients with comorbidities and cancer. The most common intervention being tested against COVID-19 are antimalarial medications with 105 clinical studies. Hydroxychloroquine is the most common drug being tested with 83 ongoing studies. Conclusion Multiple intervention based clinical studies against SARS-CoV-2 are being performed throughout the world with a high concentration of clinical trials in the developed world. There is a high concern that most of the studies maybe repetitive; elderly and patients with comorbidities are being underrepresented; definite endpoints like mortality are being assessed in only one-fifth of the studies.", "qid": 17, "docid": "feb722re", "rank": 33, "score": 6.539999961853027}, {"content": "Title: An overview of coronaviruses including the SARS-2 coronavirus \u2013 Molecular biology, epidemiology and clinical implications Content: Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.", "qid": 17, "docid": "izltn367", "rank": 34, "score": 6.5395002365112305}, {"content": "Title: An overview of coronaviruses including the SARS-2 coronavirus - Molecular biology, epidemiology and clinical implications Content: Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.", "qid": 17, "docid": "skkng2le", "rank": 35, "score": 6.539499282836914}, {"content": "Title: Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative meta-analysis between the Big data and the real world Content: In the context of the current COVID-19 pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of May, 27, 2020 The keywords \u201chydroxychloroquine\u201d, \u201cchloroquine\u201d, \u201ccoronavirus\u201d, \u201cCOVID-19\u201d and \u201cSARS-Cov-2\u201d were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language Twenty studies were identified involving 105,040 patients (19,270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain, and USA) Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favorable outcome Clinical studies were associated with favorable outcomes and details on therapy Among clinical studies, three of four randomized controlled trials reported a significant favorable effect Among clinical studies, a significant favorable summary effect was observed for duration of cough (Odds ratio (OR), 0 19, p = 00003), duration of fever (0 11, p = 039), clinical cure (0 21, p = 0495), death (0 32, p = 4 1x10-6) and viral shedding (0 43, p = 031) A trend for a favorable effect was noted for the outcome \u201cdeath and/or ICU transfer\u201d (0 29, p = 069) with a point estimate remarkably similar to that observed for death (\u223c0 3) In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes but, more importantly, it reduces mortality by a factor 3 in patients infected with COVID-19 Big data are lacking basic treatment definitions and are linked to conflict of interest", "qid": 17, "docid": "k96byjze", "rank": 36, "score": 6.5229997634887695}, {"content": "Title: Severe acute respiratory syndrome. Content: Severe acute respiratory syndrome (SARS) is a new disease that poses a threat to international health. The SARS epidemic earlier this year affected more than 30 countries and regions, with a cumulative global total of 8098 cases. It is caused by a novel coronavirus, probably of animal origin. The mean incubation period is 6.4 days (range 2-11 days). Patients usually present with high fever, chills, myalgia and dry cough, with or without chest X-ray evidence of pneumonia at the onset of disease. A history of contact with or travel to an area with local transmission is common. Diagnosis is based on clinical criteria, as a valid rapid diagnostic test is not yet available. There is no specific antiviral therapy for this disease, and no controlled clinical trial for any treatment modality has been conducted. In several retrospective studies steroids have been shown to be useful in a proportion of patients who deteriorated despite antibiotics and supportive treatment. SARS has a high morbidity (about 25% required intensive care) and fatality (9.6%). A high index of suspicion for the disease, isolation of patients, strict observation of infection control practices and compliance with use of personal protective equipment are necessary to prevent nosocomial infection. Contact tracing and quarantine are essential measures to prevent community spread of disease. Prevention of future outbreaks requires strengthening of infection control practices in hospitals, development of a rapid diagnostic test and a vaccine, and removal of any animal reservoir and environmental conditions that led to the spread of the disease.", "qid": 17, "docid": "45edcrv6", "rank": 37, "score": 6.517300128936768}, {"content": "Title: Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses. Content: OBJECTIVES To conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in mind: to clarify uncertainties about the cardiovascular risk of rosiglitazone; to determine whether different analytical approaches are likely to alter the conclusions of adverse event meta-analyses; and to inform efforts to promote clinical trial transparency and data sharing. DESIGN Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES GlaxoSmithKline's (GSK's) ClinicalStudyDataRequest.com for individual patient level data (IPD) and GSK's Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019 for summary level data. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomized, controlled, phase II-IV clinical trials that compared rosiglitazone with any control for at least 24 weeks in adults. DATA EXTRACTION AND SYNTHESIS For analyses of trials for which IPD were available, a composite outcome of acute myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death was examined. These four events were examined independently as secondary analyses. For analyses including trials for which IPD were not available, myocardial infarction and cardiovascular related death were examined, which were determined from summary level data. Multiple meta-analyses were conducted that accounted for trials with zero events in one or both arms with two different continuity corrections (0.5 constant and treatment arm) to calculate odds ratios and risk ratios with 95% confidence intervals. RESULTS 33 eligible trials were identified from ClinicalStudyDataRequest.com for which IPD were available (21 156 patients). Additionally, 103 trials for which IPD were not available were included in the meta-analyses for myocardial infarction (23 683 patients), and 103 trials for which IPD were not available contributed to the meta-analyses for cardiovascular related death (22 772 patients). Among 29 trials for which IPD were available and that were included in previous meta-analyses using GSK's summary level data, more myocardial infarction events were identified by using IPD instead of summary level data for 26 trials, and fewer cardiovascular related deaths for five trials. When analyses were limited to trials for which IPD were available, and a constant continuity correction of 0.5 and a random effects model were used to account for trials with zero events in only one arm, patients treated with rosiglitazone had a 33% increased risk of a composite event compared with controls (odds ratio 1.33, 95% confidence interval 1.09 to 1.61; rosiglitazone population: 274 events among 11 837 patients; control population: 219 events among 9319 patients). The odds ratios for myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death were 1.17 (0.92 to 1.51), 1.54 (1.14 to 2.09), 1.15 (0.55 to 2.41), and 1.18 (0.60 to 2.30), respectively. For analyses including trials for which IPD were not available, odds ratios for myocardial infarction and cardiovascular related death were attenuated (1.09, 0.88 to 1.35, and 1.12, 0.72 to 1.74, respectively). Results were broadly consistent when analyses were repeated using trials with zero events across both arms and either of the two continuity corrections was used. CONCLUSIONS The results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events. Although increased risk of myocardial infarction was observed across analyses, the strength of the evidence varied and effect estimates were attenuated when summary level data were used in addition to IPD. Because more myocardial infarctions and fewer cardiovascular related deaths were reported in the IPD than in the summary level data, sharing IPD might be necessary when performing meta-analyses focused on safety. SYSTEMATIC REVIEW REGISTRATION OSF Home https://osf.io/4yvp2/.", "qid": 17, "docid": "tffg9nch", "rank": 38, "score": 6.512899875640869}, {"content": "Title: Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19? Content: The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "qid": 17, "docid": "tasbdhs1", "rank": 39, "score": 6.503200054168701}, {"content": "Title: Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Content: BACKGROUND There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). OBJECTIVES To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control. DATA COLLECTION AND ANALYSIS Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE. MAIN RESULTS We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were available for a total of 55,614 participants. There was evidence that vitamin E supplements do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence) compared with placebo. Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty evidence). Two trials reported similar numbers of adverse events in the vitamin E and placebo groups. Another trial reported excess of haemorrhagic strokes in the vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low-certainty evidence).Two studies reported the comparison of beta-carotene with placebo. These studies took place in Finland and the USA. Both trials enrolled men only. Average treatment and follow-up duration was 6 years and 12 years. Data were available for a total of 22,083 participants. There was evidence that beta-carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high-certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI 0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very low-certainty evidence). Beta-carotene was associated with increased risk of lung cancer in people who smoked.One study reported the comparison of vitamin C with placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in men in the USA with average treatment duration and follow-up of 8 years for vitamin C and 11 years for multivitamin. Data were available for a total of 14,236 participants. AMD was assessed by self-report followed by medical record review. There was evidence that vitamin C supplementation did not prevent any AMD (RR 0.96, 95% CI 0.79 to 1.18; high-certainty evidence) or late AMD (RR 0.94, 0.61 to 1.46; moderate-certainty evidence). There was a slight increased risk of any AMD (RR 1.21, 95% CI 1.02 to 1.43; moderate-certainty evidence) and late AMD (RR 1.22, 95% CI 0.88 to 1.69; moderate-certainty evidence) in the multivitamin group. Neovascular AMD and geographic atrophy were not reported separately. Adverse effects were not reported but there was possible increased risk of skin rashes in the multivitamin group.Adverse effects were not consistently reported in these eye studies, but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke or who have been exposed to asbestos.None of the studies reported quality of life or resource use and costs. AUTHORS' CONCLUSIONS Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. The same probably applies to vitamin C and the multivitamin (Centrum Silver) investigated in the one trial reported to date. There is no evidence with respect to other antioxidant supplements, such as lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements may have harmful effects, and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane Review on antioxidant vitamin and mineral supplements for slowing the progression of AMD, written by the same review team.", "qid": 17, "docid": "51rpry20", "rank": 40, "score": 6.438199996948242}, {"content": "Title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? Content: PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. RECENT FINDINGS: In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. SUMMARY: From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.", "qid": 17, "docid": "r426u5dz", "rank": 41, "score": 6.405399799346924}, {"content": "Title: A Machine Learning alternative to placebo-controlled clinical trials upon new diseases: A primer Content: The appearance of a new dangerous and contagious disease requires the development of a drug therapy faster than what is foreseen by usual mechanisms. Many drug therapy developments consist in investigating through different clinical trials the effects of different specific drug combinations by delivering it into a test group of ill patients, meanwhile a placebo treatment is delivered to the remaining ill patients, known as the control group. We compare the above technique to a new technique in which all patients receive a different and reasonable combination of drugs and use this outcome to feed a Neural Network. By averaging out fluctuations and recognizing different patient features, the Neural Network learns the pattern that connects the patients initial state to the outcome of the treatments and therefore can predict the best drug therapy better than the above method. In contrast to many available works, we do not study any detail of drugs composition nor interaction, but instead pose and solve the problem from a phenomenological point of view, which allows us to compare both methods. Although the conclusion is reached through mathematical modeling and is stable upon any reasonable model, this is a proof-of-concept that should be studied within other expertises before confronting a real scenario. All calculations, tools and scripts have been made open source for the community to test, modify or expand it. Finally it should be mentioned that, although the results presented here are in the context of a new disease in medical sciences, these are useful for any field that requires a experimental technique with a control group.", "qid": 17, "docid": "vvm15tpc", "rank": 42, "score": 6.400000095367432}, {"content": "Title: Pathogen-reduced platelets for the prevention of bleeding. Content: BACKGROUND Platelet transfusions are used to prevent and treat bleeding in patients who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion-transmitted infections (TTIs) for which laboratory tests may not be available at the time of initial outbreak.One solution to reduce further the risk of TTIs from platelet transfusion is photochemical pathogen reduction, a process by which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf-life extension, and negate the requirement for gamma-irradiation of platelets. Although current pathogen-reduction technologies have been proven significantly to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen-reduced platelets for post-transfusion platelet recovery and the prevention of bleeding when compared with standard platelets. OBJECTIVES To assess the effectiveness of pathogen-reduced platelets for the prevention of bleeding in patients requiring platelet transfusions. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 1), MEDLINE (1950 to 18 February 2013), EMBASE (1980 to 18 February 2013), CINAHL (1982 to 18 February 2013) and the Transfusion Evidence Library (1980 to 18 February 2013). We also searched several international and ongoing trial databases and citation-tracked relevant reference lists. We requested information on possible unpublished trials from known investigators in the field. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing the transfusion of pathogen-reduced platelets with standard platelets. We did not identify any RCTs which compared the transfusion of one type of pathogen-reduced platelets with another. DATA COLLECTION AND ANALYSIS One author screened all references, excluding duplicates and those clearly irrelevant. Two authors then screened the remaining references, confirmed eligibility, extracted data and analysed trial quality independently. We requested and obtained a significant amount of missing data from trial authors. We performed meta-analyses where appropriate using the fixed-effect model for risk ratios (RR) or mean differences (MD), with 95% confidence intervals (95% CI), and used the I\u00b2 statistic to explore heterogeneity, employing the random-effects model when I\u00b2 was greater than 30%. MAIN RESULTS We included 10 trials comparing pathogen-reduced platelets with standard platelets. Nine trials assessed Intercept\u00ae pathogen-reduced platelets and one trial Mirasol\u00ae pathogen-reduced platelets. Two were randomised cross-over trials and the remaining eight were parallel-group RCTs. In total, 1422 participants were available for analysis across the 10 trials, of which 675 participants received Intercept\u00ae and 56 Mirasol\u00ae platelet transfusions. Four trials assessed the response to a single study platelet transfusion (all Intercept\u00ae) and six to multiple study transfusions (Intercept\u00ae (N = 5), Mirasol\u00ae (N = 1)) compared with standard platelets.We found the trials to be generally at low risk of bias but heterogeneous regarding the nature of the interventions (platelet preparation), protocols for platelet transfusion, definitions of outcomes, methods of outcome assessment and duration of follow-up.Our primary outcomes were mortality, 'any bleeding', 'clinically significant bleeding' and 'severe bleeding', and were grouped by duration of follow-up: short (up to 48 hours), medium (48 hours to seven days) or long (more than seven days). Meta-analysis of data from five trials of multiple platelet transfusions reporting 'any bleeding' over a long follow-up period found an increase in bleeding in those receiving pathogen-reduced platelets compared with standard platelets using the fixed-effect model (RR 1.09, 95% CI 1.02 to 1.15, I\u00b2 = 59%); however, this meta-analysis showed no difference between treatment arms when using the random-effects model (RR 1.14, 95% CI 0.93 to 1.38).There was no evidence of a difference between treatment arms in the number of patients with 'clinically significant bleeding' (reported by four out of the same five trials) or 'severe bleeding' (reported by all five trials) (respectively, RR 1.06, 95% CI 0.93 to 1.21, I\u00b2 = 2%; RR 1.27, 95% CI 0.76 to 2.12, I\u00b2 = 51%). We also found no evidence of a difference between treatment arms for all-cause mortality, acute transfusion reactions, adverse events, serious adverse events and red cell transfusion requirements in the trials which reported on these outcomes. No bacterial transfusion-transmitted infections occurred in the six trials that reported this outcome.Although the definition of platelet refractoriness differed between trials, the relative risk of this event was 2.74 higher following pathogen-reduced platelet transfusion (RR 2.74, 95% CI 1.84 to 4.07, I\u00b2 = 0%). Participants required 7% more platelet transfusions following pathogen-reduced platelet transfusion when compared with standard platelet transfusion (MD 0.07, 95% CI 0.03 to 0.11, I\u00b2 = 21%), although the interval between platelet transfusions was only shown to be significantly shorter following multiple Intercept\u00ae pathogen-reduced platelet transfusion when compared with standard platelet transfusion (MD -0.51, 95% CI -0.66 to -0.37, I\u00b2 = 0%). In trials of multiple pathogen-reduced platelets, our analyses showed the one- and 24-hour count and corrected count increments to be significantly inferior to standard platelets. However, one-hour increments were similar in trials of single platelet transfusions, although the 24-hour count and corrected count increments were again significantly lower. AUTHORS' CONCLUSIONS We found no evidence of a difference in mortality, 'clinically significant' or 'severe bleeding', transfusion reactions or adverse events between pathogen-reduced and standard platelets. For a range of laboratory outcomes the results indicated evidence of some benefits for standard platelets over pathogen-reduced platelets. These conclusions are based on data from 1422 patients included in 10 trials. Results from ongoing or new trials are required to determine if there are clinically important differences in bleeding risk between pathogen-reduced platelet transfusions and standard platelet transfusions. Given the variability in trial design, bleeding assessment and quality of outcome reporting, it is recommended that future trials apply standardised approaches to outcome assessment and follow-up, including safety reporting.", "qid": 17, "docid": "6xdo6op6", "rank": 43, "score": 6.396599769592285}, {"content": "Title: Current treatment for acute viral bronchiolitis in infants. Content: This paper provides an update and critical review of available data on the treatment of acute viral bronchiolitis in previously healthy infants, with special focus on new or promising therapies. The main potential benefits of medical assistance in these patients reside in the careful monitoring of their clinical status, the maintenance of adequate hydration and oxygenation, the preservation of the airway opened and cleared of secretions and the option to perform parental education. There is no convincing evidence that any other form of therapy will reliably provide beneficial effects in infants with bronchiolitis and currently, any treatment beyond supportive care should be prescribed on a case-by-case basis with watchful appraisal of its effects. Therapies such as ribavirin, IFN, vitamin A, antibiotics, mist therapy or anticholinergics, have not demonstrated any measurable clinical effect. Several studies and meta-analyses with beta(2)-agonists and corticosteroids have failed to show any benefit of significant extent, however, physicians keep favouring their use. Presently, adrenaline has received rather consistent support from clinical trials but it is not yet widely prescribed. There are other therapeutic strategies, for instance, heliox, hypertonic saline, noninvasive ventilation, physical therapy techniques, thickened feeds or palivizumab that have shown promising potential benefits, but evidence supporting its use is still limited and further studies should be warranted. In the meantime, infants with acute viral bronchiolitis should be treated following evidence-based clinical practice guidelines, keeping the patient central in the process and being sensitive to social, cultural and familiar influences on their treatment strategy.", "qid": 17, "docid": "0kj85fym", "rank": 44, "score": 6.371099948883057}, {"content": "Title: A living systematic review protocol for COVID-19 clinical trial registrations Content: Since the coronavirus disease 2019 (COVID-19) outbreak was identified in December 2019 in Wuhan, China, a strong response from the research community has been observed with the proliferation of independent clinical trials assessing diagnostic methods, therapeutic and prophylactic strategies. While there is no intervention for the prevention or treatment of COVID-19 with proven clinical efficacy to date, tools to distil the current research landscape by intervention, level of evidence and those studies likely powered to address future research questions is essential. This living systematic review aims to provide an open, accessible and frequently updated resource summarising the characteristics of COVID-19 clinical trial registrations. Weekly search updates of the WHO International Clinical Trials Registry Platform (ICTRP) and source registries will be conducted. Data extraction by two independent reviewers of trial characteristic variables including categorisation of trial design, geographic location, intervention type and targets, level of evidence and intervention adaptability to low resource settings will be completed. Descriptive and thematic synthesis will be conducted. A searchable and interactive visualisation of the results database will be created, and made openly available online. Weekly results from the continued search updates will be published and made available on the Infectious Diseases Data Observatory (IDDO) website ( COVID-19 website). This living systematic review will provide a useful resource of COVID-19 clinical trial registrations for researchers in a rapidly evolving context. In the future, this sustained review will allow prioritisation of research targets for individual patient data meta-analysis.", "qid": 17, "docid": "9lm0sz5p", "rank": 45, "score": 6.361999988555908}, {"content": "Title: Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines Content: Abstract Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and (3) conducting \u201cnear real-time\u201c prospective monitoring for unknown clustering\u2019s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.", "qid": 17, "docid": "bs8vqa40", "rank": 46, "score": 6.355599880218506}, {"content": "Title: Treatment and preliminary outcomes of 150 acute care patients with COVID-19 in a rural health system in the Dakotas Content: The majority of available US-published reports present populations with community spread in urban areas. The objective of this report is to describe a rural healthcare system's utilisation of therapeutic options available to treat Coronavirus Disease 2019 (COVID-19) and subsequent patient outcomes. A total of 150 patients were treated for COVID-19 at three hospitals in the Dakotas from 21 March 2020 to 30 April 2020. The most common pharmacological treatment regimens administered were zinc, hydroxychloroquine plus azithromycin and convalescent plasma. Adjunctive treatments included therapeutic anticoagulation, tocilizumab and corticosteroids. As of 1 June 2020, 127 patients have survived to hospital discharge, 12 patients remain hospitalised and 11 patients have expired. The efficacy of hydroxychloroquine and azithromycin use has yet to be determined but was not without risks of corrected QT interval prolongation and arrhythmias in our cohort. We did not appreciate any adverse effects that appeared related to tocilizumab or convalescent plasma administration in those patient subsets. These findings may provide insight into disease severity and treatment options in the rural setting with limited resources to participate in clinical trials and encourage larger comparative studies evaluating treatment efficacy.", "qid": 17, "docid": "9l0x92wi", "rank": 47, "score": 6.349100112915039}, {"content": "Title: Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204). Content: BACKGROUND Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). METHODS Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. RESULTS Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. CONCLUSIONS Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC.", "qid": 17, "docid": "4474x9nt", "rank": 48, "score": 6.332099914550781}, {"content": "Title: How to Build the Plane While Flying: VTE/PE Thromboprophylaxis Clinical Guidelines for COVID-19 Patients Content: Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.", "qid": 17, "docid": "uok8osd5", "rank": 49, "score": 6.3225998878479}, {"content": "Title: A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis Content: BACKGROUND AND OBJECTIVE: There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. The objective of this study was to describe the characteristics of the currently registered interventional clinical trials related to COVID-19. METHODS: We searched the World Health Organization's International Clinical Trials Registry Platform on May 15th, 2020. We included any entry that is related to COVID-19. We abstracted and then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. RESULTS: We identified 1,308 eligible registered trials. Most trials were registered with ClinicalTrials.gov (n = 703; 53.7%) and the Chinese Clinical Trial Registry (n = 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most commonly studied intervention category was pharmacologic (n = 763; 58.3%), with antiparasitic medications being the most common subcategory. Although over half of the trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. CONCLUSION: There is a relatively large number of registered trials but with very few results published so far. Although our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.", "qid": 17, "docid": "81dmnya4", "rank": 50, "score": 6.321800231933594}, {"content": "Title: A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis Content: Abstract Background There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the Coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. Objectives To describe the characteristics of the currently registered clinical trials related to COVID-19. Methods We searched the World Health Organization (WHO)\u2019s International Clinical Trials Registry Platform (ICTRP) on May 15, 2020. We included any entry that is related to COVID-19. We abstracted then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. Results We identified 1,308 eligible registered trials. The majority of trials were initially registered with ClinicalTrials.gov (n= 703; 53.7%) and the Chinese Clinical Trial Registry (ChiCTR) (n= 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most-commonly studied intervention category was pharmacologic (n=763; 58.3%), with antiparasitic medications being the most common subcategory. While over half of trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. Conclusion There is a relatively large number of registered trials but very few results published so far. While our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.", "qid": 17, "docid": "iy0h2pyf", "rank": 51, "score": 6.321799278259277}, {"content": "Title: Targeting the NO\u2010cGMP\u2010PDE5 pathway in COVID\u201019 infection Content: A pandemic outbreak of COVID\u201019 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, \u201ccytokines storm\u201d, that causes the systemic complications of COVID\u201019. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)\u2010cyclic GMP\u2010phosphodiesterase type 5 (PDE5) pathway in modulating low\u2010grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti\u2010inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID\u201019 disease. We performed a systematic review of all evidence documenting any involvement of the NO\u2010cGMP\u2010PDE5 axis in the pathophysiology of COVID\u201019, presenting the ongoing clinical trials aimed at modulating this axis, including our own \u201csilDEnafil administration in DiAbetic and dysmetaboLic patients with COVID\u201019 (DEDALO trial)\u201d. The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID\u201019 by (i) counteracting the Ang\u2010II\u2010mediated downregulation of AT\u20101 receptor; (ii) acting on monocyte switching, thus reducing pro\u2010inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage\u2010necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID\u201019 in developing countries.", "qid": 17, "docid": "znrhobb2", "rank": 52, "score": 6.3180999755859375}, {"content": "Title: Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (&#8805; 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) &#8804; 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for &#8805; 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 - 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 - 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 17, "docid": "2j3kdvva", "rank": 53, "score": 6.316800117492676}, {"content": "Title: Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (\u2265 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) \u2264 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for \u2265 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 \u2013 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 \u2013 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 17, "docid": "ldrbc4wt", "rank": 54, "score": 6.316799163818359}, {"content": "Title: Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment Content: Background: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing understanding of the benefit-risk balance for remdesivir in COVID-19 treatment by using a structured method which uses all available data. Methods: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared to standard of care, placebo or other treatments. We searched PubMed,Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several key benefits and risks for use of remdesivir in COVID-19 compared to placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR=1.23, 95% CI: 0.87, 1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) comparted to the placebo group (26%), however more patients in the remdesivir group discontinued treatment as a result of an adverse event compared to those patients receiving placebo (12% vs 5%). Conclusions: Preliminary clinical trial results suggest a favourable benefit-risk profile for remdesivir compared to placebo, however there is limited safety data available at the current time. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 17, "docid": "dieaqxmi", "rank": 55, "score": 6.2957000732421875}, {"content": "Title: Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China [version 1;peer review: awaiting peer review] Content: A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population Current efforts are focused on containment and quarantine of infected individuals Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s)", "qid": 17, "docid": "4bdusuqq", "rank": 56, "score": 6.268700122833252}, {"content": "Title: Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China Content: A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).", "qid": 17, "docid": "x248prxo", "rank": 57, "score": 6.2686991691589355}, {"content": "Title: Prompt closure versus gradual weaning of extraventricular drainage for hydrocephalus in adult patients with aneurysmal subarachnoid haemorrhage: a systematic review protocol with meta-analysis and trial sequential analysis. Content: INTRODUCTION In Neuro Intensive Care Units (NICU) and neurosurgical units, patients with an external ventricular drain (EVD) due to hydrocephalus following aneurysmal subarachnoid haemorrhage (SAH) are commonly seen. Cessation of the EVD involves the dilemma of either closing the EVD directly, or gradually weaning it before removal. Development of increased intracranial pressure (ICP) and acute hydrocephalus with subsequent need of a permanent shunt has been associated with prompt closure of theEVD, whereas increased risk of infection with possible spreading to the brain and subsequent patient fatality is suspected in connection to a longer treatment as seen in gradual weaning. Sparse data exist on the recommendation of cessation strategy and patients are currently being treated on the basis of personal experience and expert opinion. The objective of this systematic review is to assess the available evidence from clinical trials on the effects of prompt closure versus gradual weaning of EVD treatment for hydrocephalus in adult patients with SAH. METHODS AND ANALYSIS We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and trial sequential analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. ETHICS AND DISSEMINATION Results will be published widely according to the interest of the society. No possible impact, harm or ethical concerns are expected doing this protocol. TRIAL REGISTRATION NUMBER PROSPERO CRD42018108801.", "qid": 17, "docid": "8oswp4j4", "rank": 58, "score": 6.263700008392334}, {"content": "Title: The Battle against COVID 19 Pandemic: What we Need to Know Before we \"Test Fire\" Ivermectin. Content: The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.", "qid": 17, "docid": "ebd7n73l", "rank": 59, "score": 6.2530999183654785}, {"content": "Title: The Battle against COVID 19 Pandemic: What we Need to Know Before we \"Test Fire\" Ivermectin Content: The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.", "qid": 17, "docid": "hyztte11", "rank": 60, "score": 6.253098964691162}, {"content": "Title: Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection. The DEDALO project Content: BACKGROUND: A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, \"cytokines storm,\" that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. MATERIALS AND METHODS: We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own \"silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial).\" RESULTS: The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. DISCUSSION AND CONCLUSION: If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries.", "qid": 17, "docid": "a1wfygyy", "rank": 61, "score": 6.234300136566162}, {"content": "Title: Equitably Sharing the Benefits and Burdens of Research: Covid\u201019 Raises the Stakes Content: One of the central principles of research ethics is that the benefits and burdens of research with human participants should be equitably distributed. This principle has important implications for where research will be conducted, how participants will be recruited, what questions will be investigated, and who will control the distribution of any innovations that result. In the context of Covid\u201019, key issues include providing support to clinical trials in low\u2010 and middle\u2010income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high\u2010risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. If clinical trials are not designed with equity considerations consciously in mind, the response to the pandemic may further exacerbate disparities in health status between population groups.", "qid": 17, "docid": "mob8dbcr", "rank": 62, "score": 6.206600189208984}, {"content": "Title: Equitably Sharing the Benefits and Burdens of Research: Covid-19 Raises the Stakes Content: One of the central principles of research ethics is that the benefits and burdens of research with human participants should be equitably distributed. This principle has important implications for where research will be conducted, how participants will be recruited, what questions will be investigated, and who will control the distribution of any innovations that result. In the context of Covid-19, key issues include providing support to clinical trials in low- and middle-income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high-risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. If clinical trials are not designed with equity considerations consciously in mind, the response to the pandemic may further exacerbate disparities in health status between population groups.", "qid": 17, "docid": "of5dvq44", "rank": 63, "score": 6.206599235534668}, {"content": "Title: Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Content: BACKGROUND Planning for outbreaks of influenza is a high priority public health issue for national governments. Neuraminidase inhibitors (NIs) are thought to help reduce the symptoms of influenza with several possible mechanisms proposed. NIs have been stockpiled with a view to their widespread use in the event of a pandemic. However, the evidence base for this class of agents remains a source of debate. In a previous review we have documented substantial risks of publication bias of trials of NIs for influenza (60% of patient data from phase III treatment trials of oseltamivir have never been published) and reporting bias in the published trials. Our confidence in the conclusions of previous versions of this review has been subsequently undermined. Since we have become aware of a large number of unpublished trials of NIs in the management of influenza, this review updates and merges existing reviews in this area. OBJECTIVES To review clinical study reports of placebo-controlled randomised trials, regulatory comments and reviews ('regulatory information') of the effects of the NIs oseltamivir and zanamivir for influenza in all age groups and appraise trial programmes, rather than single studies.Clinical study reports are very detailed, unpublished clinical trial data containing in-depth descriptions of protocol rationale, methods analysis plans, trial results and organisational documents (such as contracts). A series of clinical studies designed and conducted by one sponsor represents a trial programme of a drug indication (for example treatment of influenza). SEARCH METHODS We searched trial registries, cross-referencing published and unpublished sources and corresponded with manufacturers and regulators. We searched the archives of the US Food and Drug Administration (FDA) and European and Japanese regulators. The evidence in this review reflects searches to obtain relevant information up to 12 April 2011. SELECTION CRITERIA We included regulatory information based on assessments of randomised controlled trials (RCTs) conducted in people of any age who had either confirmed or suspected influenza, or who had been exposed to influenza in the local community or place of residence. We included information which had been made available by our deadline. DATA COLLECTION AND ANALYSIS We indexed regulatory information in two purpose-built instruments and reconstructed trials using CONSORT statement-based templates. To progress to Stage 2 (full analysis) we sought manufacturer explanations of discrepancies in the data. GlaxoSmithKline (GSK) offered us individual patient data and responded to our queries, but Roche did not provide us with complete clinical study reports. In Stage 2 we intended to analyse trials with validated data (i.e. assuming our validation questions aimed at clarifying omissions and discrepancies were resolved). No studies progressed to Stage 2. We carried out analyses of the effects of oseltamivir on time to first alleviation of symptoms and hospitalisations using the intention-to-treat (ITT) population and tested five hypotheses generated post-protocol publication. MAIN RESULTS We included and analysed data from 25 studies (15 oseltamivir and 10 zanamivir studies). We could not use data from a further 42 studies due to insufficient information or unresolved discrepancies in their data. The included trials were predominantly conducted in adults during influenza seasons in both hemispheres. A small number of studies were conducted in older people residing in care homes and in people with underlying respiratory diseases. The studies had adequate randomisation and blinding procedures, but imbalances in the analysis populations available (ITT influenza-infected) left many of the studies at risk of attrition bias. All the studies were sponsored by manufacturers of NIs. Time to first alleviation of symptoms in people with influenza-like illness symptoms (i.e. ITT population) was a median of 160 hours (range 125 to 192 hours) in the placebo groups and oseltamivir shortened this by around 21 hours (95% confidence interval (CI) -29.5 to -12.9 hours, P < 0.001; five studies) but there was no evidence of effect on hospitalisations based on seven studies with a median placebo group event rate of 0.84% (range 0% to 11%): odds ratio (OR) 0.95; 95% CI 0.57 to 1.61, P = 0.86). These results are based on the comprehensive ITT population data and are unlikely to be biased. A post-protocol analysis showed that participants randomised to oseltamivir in treatment trials had a reduced odds being diagnosed with influenza (OR 0.83; 95% CI 0.73 to 0.94, P = 0.003; eight studies), probably due to an altered antibody response. Zanamivir trials showed no evidence of this. Due to limitations in the design, conduct and reporting of the trial programme, the data available to us lacked sufficient detail to credibly assess a possible effect of oseltamivir on complications and viral transmission. We postponed analysis of zanamivir evidence because of the offer of individual patient data (IPD) from its manufacturer. The authors have been unable to obtain the full set of clinical study reports or obtain verification of data from the manufacturer of oseltamivir (Roche) despite five requests between June 2010 and February 2011. No substantial comments were made by Roche on the protocol of our Cochrane Review which has been publicly available since December 2010. AUTHORS' CONCLUSIONS We found a high risk of publication and reporting biases in the trial programme of oseltamivir. Sub-population analyses of the influenza infected population in the oseltamivir trial programme are not possible because the two arms are non-comparable due to oseltamivir's apparent interference with antibody production. The evidence supports a direct oseltamivir mechanism of action on symptoms but we are unable to draw conclusions about its effect on complications or transmission. We expect full clinical study reports containing study protocol, reporting analysis plan, statistical analysis plan and individual patient data to clarify outstanding issues. These full clinical study reports are at present unavailable to us.", "qid": 17, "docid": "9i8t92ct", "rank": 64, "score": 6.201099872589111}, {"content": "Title: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials Content: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "qid": 17, "docid": "p36zubnf", "rank": 65, "score": 6.197400093078613}, {"content": "Title: Pre-operative biliary drainage for obstructive jaundice. Content: BACKGROUND Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient. OBJECTIVES To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause). SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012. SELECTION CRITERIA We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status. DATA COLLECTION AND ANALYSIS Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis. MAIN RESULTS We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60% and 100%. There was no significant difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12; 95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the pre-operative biliary drainage group (60 per 100 patients in the pre-operative biliary drainage group versus 26 per 100 patients in the direct surgery group) (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who developed serious morbidity was significantly higher in the pre-operative biliary drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not reported in any of the trials. There was no significant difference in the length of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI -1.28 to 11.02; P = 0.12) between the two groups. Trial sequential analysis showed that for mortality only a small proportion of the required information size had been obtained. There seemed to be no significant differences in the subgroup of trials assessing percutaneous compared to endoscopic drainage. AUTHORS' CONCLUSIONS There is currently not sufficient evidence to support or refute routine pre-operative biliary drainage for patients with obstructive jaundice. Pre-operative biliary drainage may increase the rate of serious adverse events. So, the safety of routine pre-operative biliary drainage has not been established. Pre-operative biliary drainage should not be used in patients undergoing surgery for obstructive jaundice outside randomised clinical trials.", "qid": 17, "docid": "b6hcipas", "rank": 66, "score": 6.196199893951416}, {"content": "Title: Early experience with convalescent plasma as immunotherapy for COVID-19 in China: Knowns and unknowns Content: BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID-19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID-19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID-19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti-epidemic strategy. MATERIALS AND METHODS: As of May 5, 2020, when the epidemic was well-controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID-19 patients. From donors, 200-400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID-19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID-19. However, there is clearly a need for well-designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.", "qid": 17, "docid": "kt70yfmt", "rank": 67, "score": 6.193299770355225}, {"content": "Title: Early experience with convalescent plasma as immunotherapy for COVID\u201019 in China: Knowns and unknowns Content: BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID\u201019), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID\u201019 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID\u201019 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti\u2010epidemic strategy. MATERIALS AND METHODS: As of May 5, 2020, when the epidemic was well\u2010controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID\u201019 patients. From donors, 200\u2013400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID\u201019 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID\u201019. However, there is clearly a need for well\u2010designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.", "qid": 17, "docid": "uqxvr77g", "rank": 68, "score": 6.193298816680908}, {"content": "Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "qid": 17, "docid": "b6aeu1ph", "rank": 69, "score": 6.184800148010254}, {"content": "Title: IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Content: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) has led to the rapid initiation of urgently needed clinical trials of repurposed drug combinations and monotherapies. These regimens were primarily relying on mechanism-of-action based selection of drugs, many of which have yielded positive in vitro but largely negative clinical outcomes. To overcome this challenge, we report the use of IDentif.AI, a platform that rapidly optimizes infectious disease (ID) combination therapy design using artificial intelligence (AI). In this study, IDentif.AI was implemented on a 12-drug candidate therapy search set representing over 530,000 possible drug combinations. IDentif.AI demonstrated that the optimal combination therapy against SARS-CoV-2 was comprised of remdesivir, ritonavir, and lopinavir, which mediated a 6.5-fold improvement in efficacy over remdesivir alone. Additionally, IDentif.AI showed hydroxychloroquine and azithromycin to be relatively ineffective. The identification of a clinically actionable optimal drug combination was completed within two weeks, with a 3-order of magnitude reduction in the number of tests typically needed. IDentif.AI analysis was also able to independently confirm clinical trial outcomes to date without requiring any data from these trials. The robustness of the IDentif.AI platform suggests that it may be applicable towards rapid development of optimal drug regimens to address current and future outbreaks.", "qid": 17, "docid": "xw8o189s", "rank": 70, "score": 6.175099849700928}, {"content": "Title: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19 Content: Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it\u2019s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government\u2019s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians\u2019 attitudes? Finally, what are the government, physicians, and patient\u2019s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government\u2019s, practitioner\u2019s and patient\u2019s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.", "qid": 17, "docid": "rffp6qe2", "rank": 71, "score": 6.161600112915039}, {"content": "Title: Immediate versus deferred delivery of the preterm baby with suspected fetal compromise for improving outcomes. Content: BACKGROUND Immediate delivery of the preterm fetus with suspected compromise may decrease the risk of damage due to intrauterine hypoxia. However, it may also increase the risks of prematurity. OBJECTIVES To assess the effects of immediate versus deferred delivery of preterm babies with suspected fetal compromise on neonatal, maternal and long-term outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 February 2012). SELECTION CRITERIA Randomised trials comparing a policy of immediate delivery with deferred delivery or expectant management in preterm fetuses with suspected in utero compromise. Quasi-randomised trials and trials employing a cluster-randomised design were eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS Two review authors independently evaluated trials for inclusion into the review. Two review authors assessed trial quality and extracted data. Data were checked for accuracy. MAIN RESULTS We included one trial of 548 women (588 babies) in the review. There was no difference in the primary outcomes of extended perinatal mortality (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.67 to 2.04) or the composite outcome of death or disability at or after two years (RR 1.22, 95% CI 0.85 to 1.75) with immediate delivery compared to deferred delivery. More babies in the immediate delivery group were ventilated for more than 24 hours (RR 1.54, 95% CI 1.20 to 1.97). There were no differences between the immediate delivery and deferred delivery groups in any other individual neonatal morbidity or markers of neonatal morbidity (cord pH less than 7.00, Apgar less than seven at five minutes, convulsions, interventricular haemorrhage or germinal matrix haemorrhage, necrotising enterocolitis and periventricular leucomalacia or ventriculomegaly).More children in the immediate delivery group had cerebral palsy at or after two years of age (RR 5.88, 95% CI 1.33 to 26.02). There were, however, no differences in neurodevelopment impairment at or after two years (RR 1.72, 95% CI 0.86 to 3.41) or death or disability in childhood (six to 13 years of age) (RR 0.82, 95% CI 0.48 to 1.40). More women in the immediate delivery group had caesarean delivery than in the deferred delivery group (RR 1.15, 95% CI 1.07 to 1.24). Data were not available on any other maternal outcomes. AUTHORS' CONCLUSIONS Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations to guide clinical practice. Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby. More research is needed to guide clinical practice.", "qid": 17, "docid": "msenf49o", "rank": 72, "score": 6.160399913787842}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Content: BACKGROUND Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.", "qid": 17, "docid": "fanupn22", "rank": 73, "score": 6.158100128173828}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review Content: BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 17, "docid": "fs8r5ze0", "rank": 74, "score": 6.158099174499512}, {"content": "Title: Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China Content: A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).", "qid": 17, "docid": "2jq626ye", "rank": 75, "score": 6.152699947357178}, {"content": "Title: Impact of balanced versus unbalanced fluid resuscitation on clinical outcomes in critically ill children: protocol for a systematic review and meta-analysis. Content: BACKGROUND Isotonic crystalloid fluid bolus therapy is used in critically ill children to restore or maintain hemodynamic stability. However, the ideal choice of crystalloid remains to be determined. The most easily available and most frequently used crystalloid is 0.9% saline, an unbalanced crystalloid, that has been associated with hyperchloremic metabolic acidosis and acute kidney injury (AKI). Balanced fluids such as Ringer's lactate (RL) were developed to be closer to the composition of serum. However, they are more expensive and less readily available than 0.9% saline. Few trials have found RL to be associated with more favorable outcomes, but pediatric data is limited and inconsistent. The objective of the present systematic review is to review existing literature to determine the effect of balanced versus unbalanced fluid bolus therapy on metabolic acidosis in critically ill children. METHODS Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines, we will conduct a systematic review to retrieve all controlled trials and observational studies comparing balanced and unbalanced resuscitative fluids in critically ill children from age 28 days to 18 years old in any resuscitation settings. Search strategy was developed in collaboration with an experienced clinical research librarian. The primary outcome is the incidence and/or time to resolution of metabolic acidosis. Secondary outcomes included the incidence of hyperchloremia, AKI, duration of renal replacement therapy, vasopressors, mechanical ventilation, total volume of rehydration needed per day, extracorporeal membrane oxygenation, and length of stay and mortality. Study screening, inclusion, data extraction, and assessment of risk of bias will be performed independently by two authors. We intend to perform a meta-analysis with studies that are compatible on the basis of population and outcomes. DISCUSSION Isotonic crystalloid fluid bolus therapy is a ubiquitous treatment in resuscitation of critically ill pediatric patients and yet there is no clear recommendation to support the choice of balanced versus unbalanced fluid. The present review will summarize current available data in the literature and assess whether recommendations can be generated regarding the choice of crystalloids or otherwise identify knowledge gaps which will open the door to a large-scale randomized controlled trial (RCT).", "qid": 17, "docid": "twcxflt3", "rank": 76, "score": 6.142300128936768}, {"content": "Title: Chloroquine and Hydroxychloroquine for the Prevention or Treatment of COVID-19 in Africa: Caution for Inappropriate Off-label Use in Healthcare Settings Content: The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.", "qid": 17, "docid": "u0pkpvg0", "rank": 77, "score": 6.127900123596191}, {"content": "Title: Effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen to treat adults with moderate to severe COVID-19: structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9(th) to April 14(th) 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: \u2265 18 years of age AND (oxygen saturation (SPO2) \u2264 93% OR respiratory rate \u2265 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of \u226537.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days \u2264 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-\u03b2 1a, Interferon-\u03b2 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-\u03b2 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-\u03b2 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan\u2013Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package \u2018randomizeR\u2019 in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9(th) April 2020 and the end date was on 14(th) April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study\u2019s follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 17, "docid": "upuaz2u0", "rank": 78, "score": 6.1097002029418945}, {"content": "Title: Effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen to treat adults with moderate to severe COVID-19: structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9th to April 14th 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: &#8805; 18 years of age AND (oxygen saturation (SPO2) &#8804; 93% OR respiratory rate &#8805; 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of &#8805;37.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days &#8804; 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-\u00df 1a, Interferon-\u00df 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-\u00df 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-\u00df 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan-Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9th April 2020 and the end date was on 14th April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study's follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 17, "docid": "va0d334p", "rank": 79, "score": 6.109699249267578}, {"content": "Title: Early Impact of COVID-19 on the Conduct of Oncology Clinical Trials and Long-Term Opportunities for Transformation: Findings From an American Society of Clinical Oncology Survey. Content: The coronavirus disease 2019 (COVID-19) pandemic has disrupted all aspects of clinical care, including cancer clinical trials. In March 2020, ASCO launched a survey of clinical programs represented on its Cancer Research Committee and Research Community Forum Steering Group and taskforces to learn about the types of changes and challenges that clinical trial programs were experiencing early in the pandemic. There were 32 survey respondents; 14 represented academic programs, and 18 represented community-based programs. Respondents indicated that COVID-19 is leading programs to halt or prioritize screening and/or enrollment for certain clinical trials and cease research-only visits. Most reported conducting remote patient care where possible and remote visits and monitoring with sponsors and/or contract research organizations (CROs); respondents viewed this shift positively. Numerous challenges with conducting clinical trials were reported, including enrollment and protocol adherence difficulties with decreased patient visits, staffing constraints, and limited availability of ancillary services. Interactions with sponsors and CROs about modifying trial procedures were also challenging. The changes in clinical trial procedures identified by the survey could serve as strategies for other programs attempting to maintain their clinical trial portfolios during the COVID-19 pandemic. Additionally, many of the adaptations to trials made during the pandemic provide a long-term opportunity to improve and transform the clinical trial system. Specific improvements could be expanded use of more pragmatic or streamlined trial designs, fewer clinical trial-related patient visits, and minimized sponsor and CRO visits to trial programs.", "qid": 17, "docid": "76gn1wnr", "rank": 80, "score": 6.1082000732421875}, {"content": "Title: Early Impact of COVID-19 on the Conduct of Oncology Clinical Trials and Long-Term Opportunities for Transformation: Findings From an American Society of Clinical Oncology Survey Content: The coronavirus disease 2019 (COVID-19) pandemic has disrupted all aspects of clinical care, including cancer clinical trials. In March 2020, ASCO launched a survey of clinical programs represented on its Cancer Research Committee and Research Community Forum Steering Group and taskforces to learn about the types of changes and challenges that clinical trial programs were experiencing early in the pandemic. There were 32 survey respondents; 14 represented academic programs, and 18 represented community-based programs. Respondents indicated that COVID-19 is leading programs to halt or prioritize screening and/or enrollment for certain clinical trials and cease research-only visits. Most reported conducting remote patient care where possible and remote visits and monitoring with sponsors and/or contract research organizations (CROs); respondents viewed this shift positively. Numerous challenges with conducting clinical trials were reported, including enrollment and protocol adherence difficulties with decreased patient visits, staffing constraints, and limited availability of ancillary services. Interactions with sponsors and CROs about modifying trial procedures were also challenging. The changes in clinical trial procedures identified by the survey could serve as strategies for other programs attempting to maintain their clinical trial portfolios during the COVID-19 pandemic. Additionally, many of the adaptations to trials made during the pandemic provide a long-term opportunity to improve and transform the clinical trial system. Specific improvements could be expanded use of more pragmatic or streamlined trial designs, fewer clinical trial-related patient visits, and minimized sponsor and CRO visits to trial programs.", "qid": 17, "docid": "fqatjip3", "rank": 81, "score": 6.108199119567871}, {"content": "Title: ChemoPROphyLaxIs with hydroxychloroquine For covId-19 infeCtious disease (PROLIFIC) to prevent covid-19 infection in frontline healthcare workers: A structured summary of a study protocol for a randomised controlled trial Content: OBJECTIVES: PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in frontline healthcare workers. SECONDARY OBJECTIVES: 1) To determine whether chemoprophylaxis with daily versus weekly dosing of hydroxychloroquine increases time to contracting COVID-19 disease in frontline healthcare workers. 2) To compare the number of COVID-19 cases between each trial arm on the basis of positive tests (as per current clinical testing methods and/or serology) 3) To compare the percentage of COVID-19 positive individuals with current testing methods versus serologically-proven COVID-19 in each trial arm 4) To compare COVID-19 disease severity in each trial arm 5) To compare recovery time from COVID-19 infection in each trial arm EXPLORATORY OBJECTIVES: 1) To determine compliance (as measured by trough pharmacokinetic hydroxychloroquine levels) on COVID-19 positive tests 2) To determine if genetic factors determine susceptibility to COVID-19 disease or response to treatment 3) To determine if blood group determines susceptibility to COVID-19 disease 4) To compare serum biomarkers of COVID-19 disease in each arm TRIAL DESIGN: Double-blind, multi-centre, 2-arm (3:3:2 ratio) randomised placebo-controlled trial PARTICIPANTS: National Health Service (NHS) workers who have direct patient contact delivering care to patients with COVID-19. Participants in the trial will be recruited from a number of NHS hospitals directly caring for patients with COVID-19. INCLUSION CRITERIA: To be included in the trial the participant MUST: 1) Have given written informed consent to participate 2) Be aged 18 years to 70 years 3) Not previously have been diagnosed with COVID-19 4) Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting COVID-19 patients) with direct patient-facing care EXCLUSION CRITERIA: The presence of any of the following will mean participants are ineligible: 1) Known COVID-19 positive test at baseline (if available) 2) Symptomatic for possible COVID-19 at baseline 3) Known hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines 4) Known retinal disease 5) Known porphyria 6) Known chronic kidney disease (CKD; eGFR<30ml/min) 7) Known epilepsy 8) Known heart failure or conduction problems 9) Known significant liver disease (Gilbert's syndrome is permitted) 10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 11) Currently taking any of the following contraindicated medications: Digoxin, Chloroquine, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel, Ciprofloxacin, Clarithromycin, Prochlorperazine, Fluconazole 12) Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine 13) Currently breastfeeding 14) Unable to be followed-up during the trial 15) Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit 16) Not able to use or have access to a modern phone device/web-based technology 17) Any other clinical reason which may preclude entry in the opinion of the investigator INTERVENTION AND COMPARATOR: Interventions being evaluated are: A) Daily hydroxychloroquine or B) Weekly hydroxychloroquine or C) Placebo The maximum treatment period is approximately 13 weeks per participant. Hydroxychloroquine-identical matched placebo tablets will ensure that all participants are taking the same number and dosing regimen of tablets across the three trial arms. There is no variation in the dose of hydroxychloroquine by weight. The dosing regimen for the three arms of the study (A, B, C) are described in further detail below. Arm A: Active Hydroxychloroquine (- daily dosing and placebo-matched hydroxychloroquine - weekly dosing). Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading phase - 400mg (2 x 200mg tablets) taken twice a day for 2 days Days 3 onwards: Maintenance Phase - 200mg (1 x 200mg tablet) taken once daily, every day for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) Arm B: Active Hydroxychloroquine (- weekly dosing and placebo matched hydroxychloroquine - daily dosing.) Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading Phase - 400mg (2 x 200mg tablets) taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 400mg (2 x 200mg tablets) taken once a week on the same day each week (every 7th day) for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Arm C: Matched placebo Hydroxychloroquine (- daily dosing and matched placebo hydroxychloroquine - weekly dosing.) Form: Table. Route: Oral. Frequency: Matched placebo hydroxychloroquine - daily dosing: Days 1-2: Loading Phase - 2 tablets taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Matched placebo hydroxychloroquine - weekly dosing: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) A schematic of the dosing schedule can be found in the full study protocol (Additional File 1). MAIN OUTCOMES: Time to diagnosis of positive COVID-19 disease (defined by record of date of symptoms onset and confirmed by laboratory test) RANDOMISATION: Participants will be randomised to either hydroxychloroquine dosed daily with weekly placebo, HCQ dosed weekly with daily placebo, or placebo dosed daily and weekly. Randomisation will be in a 3:3:2 ratio [hydroxychloroquine-(daily), hydroxychloroquine-(weekly), placebo], using stratified block randomisation. Random block sizes will be used, and stratification will be by study site. BLINDING (MASKING): Participants and trial investigators consenting participants, delivering trial assessments and procedures will be blinded to intervention. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sufficient number of participants will be enrolled so that approximately 1000 participants in total will have data suitable for the primary statistical analysis. It is anticipated that approximately 1,200 participants will need to be enrolled in total, to allow for a 20% dropout over the period of the trial. This would result in approximately 450:450:300 participants randomised to hydroxychloroquine daily, hydroxychloroquine weekly+daily matched placebo or matched-placebo daily and weekly. TRIAL STATUS: V 1.0, 7th April 2020 EU Clinical Trials Register EudraCT Number: 2020-001331-26 Date of registration: 14th April 2020 Trial registered before first participant enrolment. Trial site is Cambridge University Hospitals NHS Foundation Trust. Recruitment started on 11th May 2020. It is anticipated that the trial will run for 12 months. The recruitment end date cannot yet be accurately predicted. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).", "qid": 17, "docid": "2wb007gf", "rank": 82, "score": 6.103300094604492}, {"content": "Title: A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19 Content: Background: Although a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. Methods: A review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms \u201c2019-nCoV\u201d, \u201cCOVID-19\u201d, \u201cSARS-CoV-2\u201d, \u201cHcov-19\u201d, \u201cnew coronavirus\u201d, \u201cnovel coronavirus\u201d. We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents. Findings: Out of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). Interpretation: Numerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking. Funding: None", "qid": 17, "docid": "t1wpujpm", "rank": 83, "score": 6.098899841308594}, {"content": "Title: A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era. Content: Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "qid": 17, "docid": "bl4d808v", "rank": 84, "score": 6.097899913787842}, {"content": "Title: A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era Content: Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "qid": 17, "docid": "ykfm38tg", "rank": 85, "score": 6.097898960113525}, {"content": "Title: Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. Content: CONTEXT The findings of systematic reviews (SRs) and meta-analyses (MAs) are used for clinical decision making. The European Association of Urology has committed increasing resources into the development of high quality clinical guidelines based on such SRs and MAs. OBJECTIVE In this paper, we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office. EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible. When conducting a SR, the essential first step is to formulate a clear and answerable research question. An extensive literature search lays the foundation for evidence synthesis. Data are extracted independently by two reviewers and any disagreements are resolved by discussion or arbitration by a third reviewer. EVIDENCE SYNTHESIS In SRs, data for particular outcomes in individual randomised controlled trials may be combined statistically in a meta-analysis to increase power when the studies are similar enough. Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size, resulting in heterogeneity in outcome between studies. A number of different tools are available such as Cochrane Risk of Bias assessment tool for randomised controlled trials. In circumstances where there is too much heterogeneity, or when a review has included nonrandomised comparative studies, it is more appropriate to conduct a narrative synthesis. The GRADE tool for assessing quality of evidence strives to be a structured and transparent system, which can be applied to all evidence, regardless of quality. A SR not only identifies, evaluates, and summarises the best available evidence, but also the gaps to be targeted by future studies. CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations. PATIENT SUMMARY Clinical practice guidelines should be evidence based, and systematic reviews and meta-analyses are essential in their production. We have discussed the key steps of conducting systematic reviews and meta-analyses in this paper.", "qid": 17, "docid": "pavdvckh", "rank": 86, "score": 6.075200080871582}, {"content": "Title: Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue? Content: Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for the ongoing clinical trials in non-COVID-19 conditions. Motivated by four currently ongoing clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help; (ii) how to achieve type I error rate control, if required; (iii) how to deal with potential treatment effect heterogeneity; (iv) how to utilize early readouts; and (v) how to utilize Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.", "qid": 17, "docid": "s8p0g4r1", "rank": 87, "score": 6.07450008392334}, {"content": "Title: Potential pharmacological agents for COVID-19. Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 17, "docid": "6cm1vp7h", "rank": 88, "score": 6.064199924468994}, {"content": "Title: Potential pharmacological agents for COVID-19 Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 17, "docid": "yoo3ic2c", "rank": 89, "score": 6.064198970794678}, {"content": "Title: Remote Methods for Conducting Tobacco-Focused Clinical Trials. Content: Most tobacco-focused clinical trials are based on locally-conducted studies that face significant challenges to implementation and successful execution. These challenges include the need for large, diverse, yet still representative study samples. This often means a protracted, costly, and inefficient recruitment process. Multi-site clinical trials can overcome some of these hurdles but incur their own unique challenges. With recent advances in mobile health (mHealth) and digital technologies, there is now a promising alternative: Remote Trials. These trials are led and coordinated by a local investigative team, but are based remotely, within a given community, state, or even nation. The remote approach affords many of the benefits of multi-site trials (more efficient recruitment of larger study samples) without the same barriers (cost, multi-site management, regulatory hurdles). The Coronavirus Disease 2019 (COVID-19) global health pandemic has resulted in rapid requirements to shift ongoing clinical trials to remote delivery and assessment platforms, making methods for the conduct of remote trials even more timely. The purpose of the present manuscript it to provide an overview of available methods for the conduct of remote tobacco-focused clinical trials as well as illustrative examples of how these methods have been implemented across recently completed and ongoing tobacco studies. We focus on key aspects of the clinical trial pipeline including remote: 1) study recruitment and screening, 2) informed consent, 3) assessment, 4) biomarker collection, and 5) medication adherence monitoring.", "qid": 17, "docid": "0s70cjwi", "rank": 90, "score": 6.056700229644775}, {"content": "Title: Remote Methods for Conducting Tobacco-Focused Clinical Trials Content: Most tobacco-focused clinical trials are based on locally-conducted studies that face significant challenges to implementation and successful execution. These challenges include the need for large, diverse, yet still representative study samples. This often means a protracted, costly, and inefficient recruitment process. Multi-site clinical trials can overcome some of these hurdles but incur their own unique challenges. With recent advances in mobile health (mHealth) and digital technologies, there is now a promising alternative: Remote Trials. These trials are led and coordinated by a local investigative team, but are based remotely, within a given community, state, or even nation. The remote approach affords many of the benefits of multi-site trials (more efficient recruitment of larger study samples) without the same barriers (cost, multi-site management, regulatory hurdles). The Coronavirus Disease 2019 (COVID-19) global health pandemic has resulted in rapid requirements to shift ongoing clinical trials to remote delivery and assessment platforms, making methods for the conduct of remote trials even more timely. The purpose of the present manuscript it to provide an overview of available methods for the conduct of remote tobacco-focused clinical trials as well as illustrative examples of how these methods have been implemented across recently completed and ongoing tobacco studies. We focus on key aspects of the clinical trial pipeline including remote: 1) study recruitment and screening, 2) informed consent, 3) assessment, 4) biomarker collection, and 5) medication adherence monitoring.", "qid": 17, "docid": "4zz5ktk5", "rank": 91, "score": 6.056699275970459}, {"content": "Title: Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies Content: No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets was performed. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.", "qid": 17, "docid": "hyihoelf", "rank": 92, "score": 6.052800178527832}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans. Content: INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 17, "docid": "1yrcbm7e", "rank": 93, "score": 6.026800155639648}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans Content: INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 17, "docid": "xt8tld2i", "rank": 94, "score": 6.026799201965332}, {"content": "Title: Optimizing telemedicine to facilitate amyotrophic lateral sclerosis clinical trials Content: Amyotrophic lateral sclerosis (ALS) has the largest drug pipeline among neuromuscular diseases, with over 160 companies actively involved in ALS research. There is a growing need to recruit trial participants, but ALS patients often have limited mobility and most ALS trials are conducted in a small number of major centers. These factors effectively limit patient participation, particularly for those in rural areas. The current coronavirus disease 2019 (COVID-19) pandemic has necessitated the more widespread use of telemedicine technology for clinical care, and has prompted consideration of its increased use for clinical trials. In this opinion piece, we describe the current state of telemedicine for recruitment, consenting, and screening of participants for clinical trials. We also summarize the available data on remote administration of outcome measures. Current challenges include validation of outcome measures for remote assessment, as well as technological, regulatory, and licensure barriers.", "qid": 17, "docid": "2owfywok", "rank": 95, "score": 6.018599987030029}, {"content": "Title: Psychological therapies for anxiety and depression in children and adolescents with long-term physical conditions. Content: BACKGROUND Long-term physical conditions affect 10% to 12% of children and adolescents worldwide. These individuals are at greater risk of developing psychological problems, particularly anxiety and depression, sometimes directly related to their illness or medical care (e.g. health-related anxiety). There is limited evidence regarding the effectiveness of psychological therapies for treating anxiety and depression in this population. Therapies designed for children and adolescents without medical issues may or may not be appropriate for use with those who have long-term physical conditions. OBJECTIVES This review was undertaken to assess the effectiveness and acceptability of psychological therapies in comparison with controls (treatment-as-usual, waiting list, attention placebo, psychological placebo, or non-psychological treatment) for treating anxiety and depression in children and adolescents with long-term physical conditions. SEARCH METHODS We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 27 September 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to May 2016). In addition we searched the Web of Science (Core Collection) (12 October 2018) and conducted a cited reference search for reports of all included trials. We handsearched relevant conference proceedings, reference lists of included articles, and grey literature. SELECTION CRITERIA Randomised controlled trials (RCTs), cluster-randomised trials and cross-over trials of psychological therapies for treating anxiety or depression in children with long-term physical conditions were included. DATA COLLECTION AND ANALYSIS Abstracts and complete articles were independently reviewed by two authors. Discrepancies were addressed by a third author. Odds ratio (OR) was used for comparing dichotomous data and standardised mean differences (SMD) for comparing continuous data. Meta-analysis was undertaken when treatments, participants, and the underlying clinical question were similar. Otherwise, narrative analysis of data was undertaken. MAIN RESULTS Twenty-eight RCTs and one cross-over trial with 1349 participants were included in the review. Most participants were recruited from community settings and hospital clinics in high-income countries. For the primary outcome of treatment efficacy, short-term depression (versus any control), there was low-quality evidence from 16 trials involving 1121 participants suggesting that psychological therapies may be more effective than control therapies (SMD -0.31, 95% CI -0.59 to -0.03; I2 = 79%). For the primary outcome of treatment efficacy, short-term anxiety (versus any control), there was inadequate evidence of moderate-quality from 13 studies involving 578 participants to determine whether psychological therapies were more effective than control conditions (SMD -0.26, CI -0.59 to 0.07, I2 = 72%). Planned sensitivity analyses could not be undertaken for risk of bias due to the small number of trials that rated high for each domain. Additional sensitivity analysis demonstrated that psychological interventions specifically designed to reduce anxiety or depression were more effective than psychological therapies designed to improve other symptoms or general coping. There was some suggestion from subgroup analyses that they type of intervention (Chi\u00b2 = 14.75, df = 5 (P = 0.01), I\u00b2 = 66.1%), the severity of depression (Chi\u00b2 = 23.29, df = 4 (P = 0.0001), I\u00b2 = 82.8%) and the type of long-term physical condition (Chi\u00b2 = 10.55, df = 4 (P = 0.03), I\u00b2 = 62.1%) may have an impact on the overall treatment effect.There was qualitative (reported), but not quantitative evidence confirming the acceptability of selected psychological therapies for anxiety and depression. There was low-quality evidence that psychological therapies were more effective than control conditions in improving quality of life (SMD 1.13, CI 0.44 to 1.82, I2 = 89%) and symptoms of long-term physical conditions (SMD -0.34, CI -0.6 to -0.06, I2 = 70%), but only in the short term. There was inadequate low-quality evidence to determine whether psychological therapies were more effective than control conditions at improving functioning in either the short term or long term. No trials of therapies for addressing health-related anxiety were identified and only two trials reported adverse effects; these were unrelated to psychological therapies. Overall, the evidence was of low to moderate quality, results were heterogeneous, and only one trial had an available protocol. AUTHORS' CONCLUSIONS A limited number of trials of variable quality have been undertaken to assess whether psychological therapies are effective for treating anxiety and depression in children and adolescents with long-term physical conditions. According to the available evidence, therapies specifically designed to treat anxiety or depression (especially those based on principles of cognitive behaviour therapy (CBT)) may be more likely to work in children and adolescents who have mild to moderate levels of symptoms of these disorders, at least in the short term. There is a dearth of therapies specifically designed to treat health-related anxiety in this age group.", "qid": 17, "docid": "qyixnc9x", "rank": 96, "score": 6.017499923706055}, {"content": "Title: Occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis Content: OBJECTIVE: To examine the psychological effects on clinicians of working to manage novel viral outbreaks, and successful measures to manage stress and psychological distress. DESIGN: Rapid review and meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, PubMed/Medline, PsycInfo, Scopus, Web of Science, Embase, and Google Scholar, searched up to late March 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Any study that described the psychological reactions of healthcare staff working with patients in an outbreak of any emerging virus in any clinical setting, irrespective of any comparison with other clinicians or the general population. RESULTS: 59 papers met the inclusion criteria: 37 were of severe acute respiratory syndrome (SARS), eight of coronavirus disease 2019 (covid-19), seven of Middle East respiratory syndrome (MERS), three each of Ebola virus disease and influenza A virus subtype H1N1, and one of influenza A virus subtype H7N9. Of the 38 studies that compared psychological outcomes of healthcare workers in direct contact with affected patients, 25 contained data that could be combined in a pairwise meta-analysis comparing healthcare workers at high and low risk of exposure. Compared with lower risk controls, staff in contact with affected patients had greater levels of both acute or post-traumatic stress (odds ratio 1.71, 95% confidence interval 1.28 to 2.29) and psychological distress (1.74, 1.50 to 2.03), with similar results for continuous outcomes. These findings were the same as in the other studies not included in the meta-analysis. Risk factors for psychological distress included being younger, being more junior, being the parents of dependent children, or having an infected family member. Longer quarantine, lack of practical support, and stigma also contributed. Clear communication, access to adequate personal protection, adequate rest, and both practical and psychological support were associated with reduced morbidity. CONCLUSIONS: Effective interventions are available to help mitigate the psychological distress experienced by staff caring for patients in an emerging disease outbreak. These interventions were similar despite the wide range of settings and types of outbreaks covered in this review, and thus could be applicable to the current covid-19 outbreak.", "qid": 17, "docid": "3l2b3q3u", "rank": 97, "score": 6.015699863433838}, {"content": "Title: Cell-based therapies for COVID-19: A living systematic review Content: OBJECTIVE: This living systematic review aims to provide a timely, rigorous and continuously updated summary of the available evidence on the role of cell-based therapies in the treatment of patients with COVID-19. DATA SOURCES: We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. All the searches covered the period until April 23, 2020 (one day before submission). ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We searched for randomised trials evaluating the effect of cell-based therapies versus placebo or no treatment in patients with COVID-19. Anticipating the lack of randomised trials directly addressing this question, we also searched for trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19. Two reviewers independently screened each study for eligibility. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. RESULTS: We screened 1,043 records but no study was considered eligible. We identified 61 ongoing studies, including 39 randomised trials evaluating different types of cell-based therapies in COVID-19. CONCLUSIONS: We did not find any studies that met our inclusion criteria and hence there is no evidence to support or refute the use of cell-based therapies in the treatment of patients with COVID-19. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision makers in the near future. PROSPERO REGISTRATION NUMBER: CRD42020179711", "qid": 17, "docid": "igp1njwq", "rank": 98, "score": 6.007599830627441}, {"content": "Title: Simian adenovirus vector production for early-phase clinical trials: A simple method applicable to multiple serotypes and using entirely disposable product-contact components Content: A variety of Good Manufacturing Practice (GMP) compliant processes have been reported for production of non-replicating adenovirus vectors, but important challenges remain. Most clinical development of adenovirus vectors now uses simian adenoviruses or rare human serotypes, whereas reported manufacturing processes mainly use serotypes such as AdHu5 which are of questionable relevance for clinical vaccine development. Many clinically relevant vaccine transgenes interfere with adenovirus replication, whereas most reported process development uses selected antigens or even model transgenes such as fluorescent proteins which cause little such interference. Processes are typically developed for a single adenovirus serotype \u2013 transgene combination, requiring extensive further optimization for each new vaccine. There is a need for rapid production platforms for small GMP batches of non-replicating adenovirus vectors for early-phase vaccine trials, particularly in preparation for response to emerging pathogen outbreaks. Such platforms must be robust to variation in the transgene, and ideally also capable of producing adenoviruses of more than one serotype. It is also highly desirable for such processes to be readily implemented in new facilities using commercially available single-use materials, avoiding the need for development of bespoke tools or cleaning validation, and for them to be readily scalable for later-stage studies. Here we report the development of such a process, using single-use stirred-tank bioreactors, a transgene-repressing HEK293 cell \u2013 promoter combination, and fully single-use filtration and ion exchange components. We demonstrate applicability of the process to candidate vaccines against rabies, malaria and Rift Valley fever, each based on a different adenovirus serotype. We compare performance of a range of commercially available ion exchange media, including what we believe to be the first published use of a novel media for adenovirus purification (NatriFlo\u00ae HD-Q, Merck). We demonstrate the need for minimal process individualization for each vaccine, and that the product fulfils regulatory quality expectations. Cell-specific yields are at the upper end of those previously reported in the literature, and volumetric yields are in the range 1 \u00d7 10(13) \u2013 5 \u00d7 10(13) purified virus particles per litre of culture, such that a 2\u20134 L process is comfortably adequate to produce vaccine for early-phase trials. The process is readily transferable to any GMP facility with the capability for mammalian cell culture and aseptic filling of sterile products.", "qid": 17, "docid": "u8y47qmd", "rank": 99, "score": 5.992599964141846}, {"content": "Title: Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment Content: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. METHODS: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 17, "docid": "gxogowwb", "rank": 100, "score": 5.980100154876709}]}
{"query": "what are the best masks for preventing infection by Covid-19?", "hits": [{"content": "Title: Is wearing a face mask safe for people with epilepsy? Content: Since December 2019, the world has been experiencing a catastrophic pandemic of coronavirus disease (COVID-19) caused by SARS-CoV2. This virus primarily targets the human respiratory system. Available information suggests that people with epilepsy (PWE) are not at higher risk of being infected by the virus, nor of more severe COVID-19 manifestations, as a result of the epilepsy alone. However, COVID-19 is a serious disease that currently has no effective treatment or vaccine. A face mask is probably effective in preventing the spread of a respiratory pathogen, at least to some extent. So, should we recommend wearing a face mask to all during a pandemic of respiratory infectious disease (e.g., COVID-19) without any precautions or exemptions? While concrete evidence is lacking, if we consider that wearing a face mask may simulate hyperventilation, at least to some extent, we would probably avoid recommending this practice indiscriminately to all PWE. On the other hand, in the absence of any proven treatment or vaccine to combat COVID-19, prevention is the best available strategy and it is probably not reasonable to suggest avoid wearing face masks in PWE under any circumstances. Logically, PWE do not need to wear a face mask most of the time, as long as there is no close contact with others, especially during intense physical activities such as exercise. To the contrary, it is probably more advantageous to wear a face mask in crowded locations, with intermittent breaks in safe locations, away from others.", "qid": 18, "docid": "lq7bh1sl", "rank": 1, "score": 9.519800186157227}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation Content: As the world confronts coronavirus disease 2019 (COVID-19), an illness caused by yet another emerging pathogen (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), obstetric care providers are asking what this means for pregnant women. The global spread has been swift, and many key questions remain. The case-fatality rate for persons cared for in the United States and whether asymptomatic persons transmit the virus are examples of questions that need to be answered to inform public health control measures. There are also unanswered questions specific to pregnant women, such as whether pregnant women are more severely affected and whether intrauterine transmission occurs. Although guidelines for pregnant women from the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have been rapidly developed based on the best available evidence, additional information is critically needed to inform key decisions, such as whether pregnant health care workers should receive special consideration, whether to temporarily separate infected mothers and their newborns, and whether it is safe for infected women to breastfeed. Some current recommendations are well supported, based largely on what we know from seasonal influenza: patients should avoid contact with ill persons, avoid touching their face, cover coughs and sneezes, wash hands frequently, disinfect contaminated surfaces, and stay home when sick. Prenatal clinics should ensure all pregnant women and their visitors are screened for fever and respiratory symptoms, and symptomatic women should be isolated from well women and required to wear a mask. As the situation with COVID-19 rapidly unfolds, it is critical that obstetricians keep up to date.", "qid": 18, "docid": "8patrxld", "rank": 2, "score": 9.51200008392334}, {"content": "Title: Use of N95, Surgical, and Cloth Masks to Prevent COVID-19 in Health Care and Community Settings: Living Practice Points From the American College of Physicians (Version 1) Content: Controversy exists around the appropriate types of masks and the situations in which they should be used in community and health care settings for the prevention of SARS-CoV-2 infection. In this article, the American College of Physicians (ACP) provides recommendations based on the best available evidence through 14 April 2020 on the effectiveness of N95 respirators, surgical masks, and cloth masks in reducing transmission of infection. The ACP plans periodic updates of these recommendations on the basis of ongoing surveillance of the literature for 1 year from the initial search date.", "qid": 18, "docid": "f4sd7vbi", "rank": 3, "score": 9.500100135803223}, {"content": "Title: The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness. Content: Background Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. Methods We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Findings Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR= 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. Interpretation We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "qid": 18, "docid": "1q8tqeg7", "rank": 4, "score": 9.270999908447266}, {"content": "Title: The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness Content: Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "qid": 18, "docid": "334hmwmj", "rank": 5, "score": 9.27099895477295}, {"content": "Title: The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness Content: Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46\u201391) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28\u20130.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "qid": 18, "docid": "no8bgglk", "rank": 6, "score": 9.270998001098633}, {"content": "Title: Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda Content: Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.", "qid": 18, "docid": "zwyueevh", "rank": 7, "score": 9.09280014038086}, {"content": "Title: What is required to prevent a second major outbreak of the novel coronavirus SARS-CoV-2 upon lifting the metropolitan-wide quarantine of Wuhan city, China Content: Background: The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Method: We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results: We estimated that at the end of the epidemic, a total of 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) would be infected through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff members). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. For an early lifting date (21st March), facial mask needed to be sustained at a relatively high rate (\u226585%) if public contacts were to recover to 100% of the pre-quarantine level. In contrast, lifting the quarantine on 18th April allowed public person-to-person contact adjusted back to the pre-quarantine level with a substantially lower level of facial mask usage (75%). However, a low facial mask usage (<50%) combined with an increased public contact (>100%) would always lead a significant second outbreak in most quarantine lifting scenarios. Lifting the quarantine on 25th April would ensure a smooth decline of the epidemics regardless of the combinations of public contact rates and facial mask usage. Conclusion: The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.", "qid": 18, "docid": "vw4vul5j", "rank": 8, "score": 9.086099624633789}, {"content": "Title: COVID-19: emerging protective measures Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 18, "docid": "qi8x5yaq", "rank": 9, "score": 9.035099983215332}, {"content": "Title: COVID-19: emerging protective measures. Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 18, "docid": "tfrawa9z", "rank": 10, "score": 9.035099029541016}, {"content": "Title: What Is Required to Prevent a Second Major Outbreak of SARS-CoV-2 upon Lifting Quarantine in Wuhan City, China Content: Summary Background The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Methods We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases in late April 2020. At the end of the epidemic, 65,733 (45,722-99,015) individuals would be infected by the virus, among which 16,166 (11,238-24,603, 24.6%) were through public contacts, 45,996 (31,892-69,565, 69.7%) through household contact, and 3,571 (2,521-5,879, 5.5%) through hospital contacts (including 778 (553-1,154) non-COVID-19 patients and 2,786 (1,969-4,791) medical staff). A total of 2,821 (1,634-6,361) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21st March is viable only if Wuhan residents sustain a high facial mask usage of \u226585% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to \u226575% at the same contact rate. Conclusions The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.", "qid": 18, "docid": "brt7ud3u", "rank": 11, "score": 8.902600288391113}, {"content": "Title: Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants Content: COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.", "qid": 18, "docid": "ej76fsxa", "rank": 12, "score": 8.630399703979492}, {"content": "Title: Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach() Content: The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. \u201cAssortment\u201d within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.", "qid": 18, "docid": "dt2pew66", "rank": 13, "score": 8.507699966430664}, {"content": "Title: [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19]. Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 18, "docid": "nk95dyln", "rank": 14, "score": 8.424699783325195}, {"content": "Title: Rationeel gebruik van ademhalingsbeschermingsmaskers./ [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19] Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 18, "docid": "31fnbch7", "rank": 15, "score": 8.390600204467773}, {"content": "Title: Nursing care for patients with COVID-19 on extracorporeal membrane oxygenation (ECMO) support Content: In Japan, four medical facilities including our own - the National Center for Global health and Medicine (NCGM) - have been designated for the treatment of specified infectious diseases by the Minister of Health, Labour, and Welfare Here, we report our nursing care for patients with severe COVID-19 on extracorporeal membrane oxygenation (ECMO) support In addition to infection control measures in the form of an N95 mask, a water-repellent isolation gown, a cap, a shielded mask on top of the N95, and double-layered gloves, nurses were required to wear one-piece suits (DuPont\u2122 Tyvek\u00ae) and use powered air-purifying respirators (PAPRs) While closed system catheters are normally changed once a day to limit aerosol exposure, they are now changed once every 4 days Nursing care included equipment checks, monitoring of hemodynamics and respiratory status, management of anticoagulants, observation of the patient\u2019s general condition, management of sedatives and analgesics, prevention of medical device-related pressure ulcers and bedsores, and maintenance of hygiene Fundamentally sound nursing remains the best practice for patient treatment and management During nursing care for patients with COVID-19 on ECMO, infection control measures should be faithfully and properly followed", "qid": 18, "docid": "u0bygcv2", "rank": 16, "score": 8.371000289916992}, {"content": "Title: The COVID\u201019 epidemic of manuscripts Content: In the midst of the novel coronavirus pandemic\u2014referred to as COVID\u201019\u2014there has been much uncertainty. We remain uncertain about its precise origin, its structure and composition, how best to test for it, or for resulting immunity, whether or not exposure leads to immunity, whether or not disposable surgical masks are effective, why men and some ethnic minorities are more susceptible and just exactly what the death rate as a result of this virus is. However, one thing is absolutely clear, there has been an epidemic of manuscripts on the subject of COVID\u201019 to nursing journals and, amongst these new manuscripts the rejection rate is, unfortunately, very high.", "qid": 18, "docid": "5d7zien3", "rank": 17, "score": 8.357000350952148}, {"content": "Title: Risk of Transmission of infection to Healthcare Workers delivering Supportive Care for Coronavirus Pneumonia;A Rapid GRADE Review Content: Abstract Background: Avenues of treatment currently implemented for Covid-19 pandemic are largely supportive in nature. Non -availability of an effective antiviral treatment makes supportive care for acute hypoxic respiratory failure is the most crucial intervention. Highly contagious nature of Covid-19 had created stress and confusion among front line Health Care Workers (HCWs) regarding infectious risk of supportive interventions and best preventive strategies. Purpose: To analyze and summarize key evidence from published literature exploring the risk of transmission of Covid-19 related to common supportive care interventions in hospitalized patients and effectiveness of currently used preventive measures in hospital setting. Data Sources: Curated Covid-19 literature from NCBI Computational Biology Branch ,Embase and Ovid till May 20,2020.Longitudinal and reference search till June 28,2020 Study Selection: Studies pertaining to risk of infection to HCWs providing standard supportive care of hospitalized Covid-19 mainly focusing on respiratory support interventions.Indirect studies from SARS,MERS or other ARDS pathology caused by infectious agents based on reference tracking and snow ball search . Clinical, Healthy volunteer and mechanistic studies were included. Two authors independently screened studies for traditional respiratory supportive-care (Hypoxia management, ventilatory support and pulmonary toileting) related transmission of viral or bacterial pneumonia to HCWs. Data Extraction: Two authors (TK and SP) independently screened articles and verified for consensus. Quality of studies and level of evidence was assessed using Oxford Center for Evidence Based Medicine (OCEBM) , Newcastle - Ottawa quality assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence. Data Synthesis: 21 studies were eligible for inclusion. In 11 mechanistic studies, 7 were manikin based,1 was in the setting of GNB pneumonia ,2 were healthy volunteer study and 1 was heterogenous setting.Out of 10 clinical studies ,5 were case controlled and 6 were cohort studies. Risk of corona virus transmission was significantly high in HCWs performing or assisting endotracheal intubation or contact with respiratory secretion.(Moderate certainty evidence, GRADE B) Safety of nebulization treatment in corona virus pneumonia patients are questionable(Low certainty evidence, GRADE C).Very low certainty evidence exist for risk of transmission with conventional HFNC (GRADE D) and NIV (GRADE D),CPR (GRADE D),Bag and mask ventilation(GRADE D).Moderate certainty evidence exist for protective effect of wearing a multilayered mask, gown , eye protection and formal training for PPE use (GRADE B).Low certainty evidence exist for transmission risk with bag and mask ventilation, suctioning before and after intubation and prolonged exposure (GRADE C).Certainty of evidence for wearing gloves,post exposure hand washing and wearing N 95 mask is low(GRADE C). Limitations: This study was limited to articles with English abstract. Highly dynamic nature of body of literature related to Covid-19, frequent updates were necessary even during preparation of manuscript and longitudinal search was continued even after finalizing initial search. Due to the heterogeneity and broad nature of the search protocol, quantitative comparisons regarding the effectiveness of included management strategies could not be performed. Direct evidence was limited due to poor quality and non-comparative nature of available Covid-19 reporting. Conclusions: Major risk factors for transmission of corona virus infection were, performing or assisting endotracheal intubation and contact with respiratory secretion. Risk of transmission with HFNC or NIV can be significantly decreased by helmet interface, modified exhalation circuit or placing a properly fitting face mask over patient interface of HFNC. Evidence for risk of transmission with CPR, suctioning before or after intubation or bag and mask ventilation of very low certainty. Significant protective factors are Formal training for PPE use, consistently wearing mask, gown and eye protection. Primary Funding Source: None Disclosure: None of the authors have any conflict of interest to disclose.", "qid": 18, "docid": "0hki5u13", "rank": 18, "score": 8.27560043334961}, {"content": "Title: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0\u00b718, 95% CI 0\u00b709 to 0\u00b738; risk difference [RD] \u221210\u00b72%, 95% CI \u221211\u00b75 to \u22127\u00b75; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2\u00b702 per m; p(interaction)=0\u00b7041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0\u00b715, 95% CI 0\u00b707 to 0\u00b734, RD \u221214\u00b73%, \u221215\u00b79 to \u221210\u00b77; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12\u201316-layer cotton masks; p(interaction)=0\u00b7090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0\u00b722, 95% CI 0\u00b712 to 0\u00b739, RD \u221210\u00b76%, 95% CI \u221212\u00b75 to \u22127\u00b77; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.", "qid": 18, "docid": "8ko7mmu3", "rank": 19, "score": 8.246800422668457}, {"content": "Title: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25\u00e2\u0080\u0088697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10\u00e2\u0080\u0088736, pooled adjusted odds ratio [aOR] 0\u00b718, 95% CI 0\u00b709 to 0\u00b738; risk difference [RD] -10\u00b72%, 95% CI -11\u00b75 to -7\u00b75; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2\u00b702 per m; pinteraction=0\u00b7041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0\u00b715, 95% CI 0\u00b707 to 0\u00b734, RD -14\u00b73%, -15\u00b79 to -10\u00b77; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12-16-layer cotton masks; pinteraction=0\u00b7090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0\u00b722, 95% CI 0\u00b712 to 0\u00b739, RD -10\u00b76%, 95% CI -12\u00b75 to -7\u00b77; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.", "qid": 18, "docid": "zzumi9h5", "rank": 20, "score": 8.24679946899414}, {"content": "Title: The covid\u201019 pandemic, personal protective equipment, and respirator: a narrative review Content: The coronavirus disease 2019 (COVID\u201019) pandemic has touched almost every continent. Personal protective equipment (PPE) is the final line of protection of healthcare workers (HCW). There is variation as well as controversy of infection control recommendation with regards to the use of PPE for HCW between institutions. The aim of this narrative review is to of examine and summarise the available evidence to guide recommendation for the safety of HCW. A literature search was conducted on the PubMed, MedLine, and Embase databases with the keywords \u201cpersonal protective equipment\u201d, \u201cCOVID 19\u201d, \u201cn95\u201d, \u201chealth care worker\u201d, and \u201cmortality\u201d. SARS\u2010nCoV\u20102 is highly contagious. 3.5\u201020% of HCW has been reported to be infected. The mortality ranges from 0.53\u20101.94%. PPE is part of the measure within a package of prevention and control of pandemic, rather than a replacement of. Respirators are more effective than masks in preventing aerosol transmission to HCWs. Extended use may be considered if guidelines are adhered. PAPRs if available should be used in high risk procedures. Transmission of viruses is multimodal, and in the setting of a novel pathogen with high case fatality with no proven effective interventions, PPE that affords the best protection should be available to HCWs.", "qid": 18, "docid": "xeyfkjm5", "rank": 21, "score": 8.191900253295898}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child's will must not be forced.Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation. What is Known: \u00e2\u0080\u00a2 Asymptomatic people can transmit and become important sources of COVID-19. \u00e2\u0080\u00a2 Asymptomatic cases are common also in pediatrics. What is New: \u00e2\u0080\u00a2 Universal use of face masks for success against COVID-19 seems necessary also in pediatric age when people have to go out in their everyday lives. \u00e2\u0080\u00a2 In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons with the main aim to obtain child cooperation.", "qid": 18, "docid": "471z07ac", "rank": 22, "score": 8.180999755859375}, {"content": "Title: About coronavirus disease 2019 (CoviD-19) Content: SARS-CoV-2 virus continues to be a worldwide public health threat During the early stages of a pandemic with sparse knowledge about the pathogen, limiting testing capacity, and without effective treatment options, it is a nearly impossible task for local and state governments to limit CoViD-19 associated morbidity and mortality in their jurisdictions To predict the numbers of infected persons, hospitalizations, and deaths, infectious disease models are useful tools for Public Health officials to decide on best public health mitigation measures to prevent the rapid growth of CoViD-19 disease The goal is to delay the rapid spread of the disease,\u201dflatten the curve,\u201d to have sufficient healthcare resources such as Intensive Care Units (ICU) beds and ventilators available to treat the very sick patients but also enough personal protective equipment (PPE) such as N95 masks, gloves, and gowns to protect the healthcare workers from getting infected", "qid": 18, "docid": "bg1q9gra", "rank": 23, "score": 8.147100448608398}, {"content": "Title: Associations between wearing masks, washing hands, and social distancing practices, and risk of COVID-19 infection in public: a cohort-based case-control study in Thailand Content: Objective. To investigate whether wearing masks, washing hands and social distancing practices are associated with lower risk of COVID-19 infection. Design. A retrospective cohort-based case-control study. All participants were retrospectively interviewed by phone about their preventive measures against COVID-19 infection. Setting. Thailand, using the data from contact tracing of COVID-19 patients associated with nightclub, boxing stadium and state enterprise office clusters from the Surveillance Rapid Response Team, Department of Disease Control, Ministry of Public Health. Contacts were tested for COVID-19 using PCR assays per national contact tracing guidelines. Participants. A cohort of 1,050 asymptomatic contacts of COVID-19 patients between 1 and 31 March 2020. Main outcome measures. Diagnosis of COVID-19 by 21 April 2020. Odds ratios for COVID-19 infection and population attributable fraction were calculated. Exposure. The study team retrospectively asked about wearing masks, washing hands, and social distancing practices during the contact period through telephone interviews. Results. Overall, 211 (20%) were diagnosed with COVID-19 by 21 Apr 2020 (case group) while 839 (80%) were not (control group). Fourteen percent of cases (29/210) and 24% of controls (198/823) reported wearing either non-medical or medical masks all the time during the contact period. Wearing masks all the time (adjusted odds ratio [aOR] 0.23; 95%CI 0.09-0.60) was associated with lower risk of COVID-19 infections compared to not wearing masks, while wearing masks sometimes (aOR 0.87; 95%CI 0.41-1.84) was not. Shortest distance of contact >1 meter (aOR 0.15; 95%CI 0.04-0.63), duration of close contact [\u2264]15 minutes (aOR 0.24; 95%CI 0.07-0.90) and washing hands often (aOR 0.33; 95%CI 0.13-0.87) were significantly associated with lower risk of infection. Sharing a cigarette (aOR 3.47; 95%CI 1.09-11.02) was associated with higher risk of infection. Type of mask was not independently associated with risk of infection. Those who wore masks all the time were more likely to wash hands and practice social distancing. We estimated that if everyone wore a mask all the time, washed hands often, did not share a dish, cup or cigarette, had shortest distance of contact >1 meter and had duration of close contact [\u2264]15 minutes, cases would have been reduced by 84%. Conclusions. Our findings support consistently wearing non-medical masks, washing hands, and social distancing in public to prevent COVID-19 infections.", "qid": 18, "docid": "l8y9r8cp", "rank": 24, "score": 8.136099815368652}, {"content": "Title: Promoting best practices for control of respiratory infections: collaboration between primary care and public health services. Content: OBJECTIVE To determine the effectiveness of a short-term intervention to promote best practices for control of respiratory infections in primary care physicians' offices. DESIGN Before-after observational study. SETTING Family physicians' offices in Ottawa, Ont. PARTICIPANTS General practitioners and office staff. INTERVENTIONS Four infection-control practices (use of masks, alcohol-based hand gel, and signs, and asking patients to sit at least 1 m apart in the waiting room) were observed, and 2 reported infection-control practices (disinfecting surfaces and use of hand-gel dispensers in examining rooms) were audited before the intervention and 6 weeks after the intervention. MAIN OUTCOME MEASURES Percentage of patients asked to use masks and alcohol-based hand gel, number of relevant signs, and percentage of patients asked to sit at least 1 m away from other patients. Percentage of surfaces disinfected and percentage of physicians using hand-gel dispensers in examining rooms. RESULTS Of 242 practices invited, 53 agreed to participate (22% response rate), and within those practices, 143/151 (95%) physicians participated. Signs regarding respiratory infection control measures increased from 15.4% to 81.1% following the intervention (P < .001). At least 1 patient with cough and fever was given a mask in 17% of practices before the intervention; during the observation period after the intervention, at least 1 patient was given a mask in 66.7% of practices (P < .001). Patients were instructed to use alcohol-based hand gel in 24.5% of practices before the intervention and in 79.2% of practices after it (P < .001). Instruction to sit at least 1 m from others in the waiting area was given in 39.6% of practices before the intervention and in 52.8% of practices following the intervention (P < .001). Before the intervention, the percentage of practices using all 4 audited primary prevention measures was 3.8%; after the intervention, 52.8% of practices were using them (P < .001), demonstrating a 49% increase in adoption of best practices. CONCLUSION A multifaceted intervention by public health nurses successfully promoted best practices for control of respiratory infections in primary care offices. Collaboration between public health services and primary care can promote best practices and warrants further study and development in areas of common interest.", "qid": 18, "docid": "0mcixa4c", "rank": 25, "score": 8.135100364685059}, {"content": "Title: Masked Face Recognition Dataset and Application Content: In order to effectively prevent the spread of COVID-19 virus, almost everyone wears a mask during coronavirus epidemic. This almost makes conventional facial recognition technology ineffective in many cases, such as community access control, face access control, facial attendance, facial security checks at train stations, etc. Therefore, it is very urgent to improve the recognition performance of the existing face recognition technology on the masked faces. Most current advanced face recognition approaches are designed based on deep learning, which depend on a large number of face samples. However, at present, there are no publicly available masked face recognition datasets. To this end, this work proposes three types of masked face datasets, including Masked Face Detection Dataset (MFDD), Real-world Masked Face Recognition Dataset (RMFRD) and Simulated Masked Face Recognition Dataset (SMFRD). Among them, to the best of our knowledge, RMFRD is currently theworld's largest real-world masked face dataset. These datasets are freely available to industry and academia, based on which various applications on masked faces can be developed. The multi-granularity masked face recognition model we developed achieves 95% accuracy, exceeding the results reported by the industry. Our datasets are available at: https://github.com/X-zhangyang/Real-World-Masked-Face-Dataset.", "qid": 18, "docid": "oid5bok9", "rank": 26, "score": 8.133700370788574}, {"content": "Title: Achieving a Covid-19 Free Country: Citizens Preventive Measures and Communication Pathways. Content: The Coronavirus Disease 2019 (COVID-19) has spread on a global scale in an extremely short time, causing hundreds of thousands of deaths, and, at the same time, triggering extreme panic. Prevention in medicine is considered the best protection action for individuals in order to avoid infections. This study investigates whether Greek citizens (N = 3359) take the necessary precautions to prevent developing the COVID-19 disease, and it segments them based on homogenous behavior groups. Lastly, it provides communication techniques that should be implemented, targeting each citizen segment for a long-term COVID-19 free country. Data analysis revealed the extent of the applied precaution measures. The ones most applied by citizens were to avoid non-mandatory transportation, contact with individuals with respiratory symptoms, and individuals of high risk for severe illness (vulnerable groups). On the other hand, the least applied measures are daily checks of body temperature, monitoring for fever, cough, or dyspnea, use of a face mask when in public places, or when using public transportation. Additionally, cluster analysis revealed five groups of citizens based on self-reported behavior, namely, the Meticulous Proactive Citizens, the Self-isolated Citizens, the Cautious Citizens, the Occasionally Cautious Citizens, and the Unconcerned Citizens. Communication strategies targeting each segment are also discussed.", "qid": 18, "docid": "kjpowgix", "rank": 27, "score": 8.132399559020996}, {"content": "Title: Achieving a Covid-19 Free Country: Citizens Preventive Measures and Communication Pathways Content: The Coronavirus Disease 2019 (COVID-19) has spread on a global scale in an extremely short time, causing hundreds of thousands of deaths, and, at the same time, triggering extreme panic. Prevention in medicine is considered the best protection action for individuals in order to avoid infections. This study investigates whether Greek citizens (N = 3359) take the necessary precautions to prevent developing the COVID-19 disease, and it segments them based on homogenous behavior groups. Lastly, it provides communication techniques that should be implemented, targeting each citizen segment for a long-term COVID-19 free country. Data analysis revealed the extent of the applied precaution measures. The ones most applied by citizens were to avoid non-mandatory transportation, contact with individuals with respiratory symptoms, and individuals of high risk for severe illness (vulnerable groups). On the other hand, the least applied measures are daily checks of body temperature, monitoring for fever, cough, or dyspnea, use of a face mask when in public places, or when using public transportation. Additionally, cluster analysis revealed five groups of citizens based on self-reported behavior, namely, the Meticulous Proactive Citizens, the Self-isolated Citizens, the Cautious Citizens, the Occasionally Cautious Citizens, and the Unconcerned Citizens. Communication strategies targeting each segment are also discussed.", "qid": 18, "docid": "o6t05a14", "rank": 28, "score": 8.13239860534668}, {"content": "Title: The Flow Physics of COVID-19 Content: Flow physics plays a key role in nearly every facet of the COVID-19 pandemic. This includes the generation and aerosolization of virus-laden respiratory droplets from a host, its airborne dispersion and deposition on surfaces, as well as the subsequent inhalation of these bioaerosols by unsuspecting recipients. Fluid dynamics is also key to preventative measures such as the use of face masks, hand-washing, ventilation of indoor environments, and even social distancing. This article summarizes what we know, and more importantly, what we need to learn about the science underlying these issues so that we are better prepared to tackle the next outbreak of COVID-19 or a similar disease.", "qid": 18, "docid": "7is71518", "rank": 29, "score": 8.111100196838379}, {"content": "Title: What association do political interventions, environmental and health variables have with the number of Covid-19 cases and deaths? A linear modeling approach Content: Background: It is unclear which variables contribute to the variance in Covid-19 related deaths and Covid-19 cases. Method: We modelled the relationship of various predictors (health systems variables, population and population health indicators) together with variables indicating public health measures (school closures, border closures, country lockdown) in 40 European and other countries, using Generalized Linear Models and minimized information criteria to select the best fitting and most parsimonious models. Results: We fitted two models with log-linearly linked variables on gamma-distributed outome variables (CoV2 cases and Covid-19 related deaths, standardized on population). Population standardized cases were best predicted by number of tests, life-expectancy in a country, and border closure (negative predictor, i.e. preventive). Population standardized deaths were best predicted by time, the virus had been in the country, life expectancy, smoking (negative predictor, i.e. preventive), and school closures (positive predictor, i.e. accelerating). Model fit statistics and model adequacy were good. Discussion and Interpretation: Interestingly, none of the variables that code for the preparedness of the medical system, for health status or other population parameters were predictive. Of the public health variables only border closure had the potential of preventing cases and none were predictors for preventing deaths. School closures, likely as a proxy for social distancing, was associated with increased deaths. Conclusion: The pandemic seems to run its autonomous course and only border closure has the potential to prevent cases. None of the contributes to preventing deaths.", "qid": 18, "docid": "cmqj8get", "rank": 30, "score": 8.106300354003906}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 18, "docid": "kshjqsdj", "rank": 31, "score": 8.054200172424316}, {"content": "Title: Dentists' Awareness, Perception, and Attitude Regarding COVID-19 and Infection Control: Cross-Sectional Study Among Jordanian Dentists Content: BACKGROUND: Despite the availability of prevention guidelines and recommendations on infection control, many dental practices lack the minimum requirements for infection control. OBJECTIVE: This study aimed to assess the level of awareness, perception, and attitude regarding the coronavirus disease (COVID-19) and infection control among Jordanian dentists. METHODS: The study population consisted of dentists who worked in private clinics, hospitals, and health centers in Jordan. An online questionnaire was sent to a sample of Jordanian dentists in March 2020. The questionnaire was comprised of a series of questions about dentists' demographic characteristics; their awareness of the incubation period, the symptoms of the disease, mode of transmission of COVID-19 and infection control measures for preventing COVID-19; and their attitude toward treating patients with COVID-19. RESULTS: This study included a total of 368 dentists aged 22-73 years (mean 32.9 years, SD 10.6 years). A total of 112 (30.4%) dentists had completed a master or residency program in dentistry, 195 (53.0%) had received training in infection control in dentistry, and 28 (7.6%) had attended training or lectures regarding COVID-19. A total of 133 (36.1%) dentists reported that the incubation period is 1-14 days. The majority of dentists were aware of COVID-19 symptoms and ways of identifying patients at risk of having COVID-19, were able to correctly report known modes of transmission, and were aware of measures for preventing COVID-19 transmission in dental clinics. A total of 275 (74.7%) believed that it was necessary to ask patients to sit far from each other, wear masks while in the waiting room, and wash hands before getting in the dental chair to decrease disease transmission. CONCLUSIONS: Jordanian dentists were aware of COVID-19 symptoms, mode of transmission, and infection controls and measures in dental clinics. However, dentists had limited comprehension of the extra precautionary measures that protect the dental staff and other patients from COVID-19. National and international guidelines should be sent by the regional and national dental associations to all registered dentists during a crisis, including the COVID-19 pandemic, to make sure that dentists are well informed and aware of best practices and recommended disease management approaches.", "qid": 18, "docid": "d0fere1l", "rank": 32, "score": 8.044500350952148}, {"content": "Title: Dentists\u2019 Awareness, Perception, and Attitude Regarding COVID-19 and Infection Control: Cross-Sectional Study Among Jordanian Dentists Content: BACKGROUND: Despite the availability of prevention guidelines and recommendations on infection control, many dental practices lack the minimum requirements for infection control. OBJECTIVE: This study aimed to assess the level of awareness, perception, and attitude regarding the coronavirus disease (COVID-19) and infection control among Jordanian dentists. METHODS: The study population consisted of dentists who worked in private clinics, hospitals, and health centers in Jordan. An online questionnaire was sent to a sample of Jordanian dentists in March 2020. The questionnaire was comprised of a series of questions about dentists\u2019 demographic characteristics; their awareness of the incubation period, the symptoms of the disease, mode of transmission of COVID-19 and infection control measures for preventing COVID-19; and their attitude toward treating patients with COVID-19. RESULTS: This study included a total of 368 dentists aged 22-73 years (mean 32.9 years, SD 10.6 years). A total of 112 (30.4%) dentists had completed a master or residency program in dentistry, 195 (53.0%) had received training in infection control in dentistry, and 28 (7.6%) had attended training or lectures regarding COVID-19. A total of 133 (36.1%) dentists reported that the incubation period is 1-14 days. The majority of dentists were aware of COVID-19 symptoms and ways of identifying patients at risk of having COVID-19, were able to correctly report known modes of transmission, and were aware of measures for preventing COVID-19 transmission in dental clinics. A total of 275 (74.7%) believed that it was necessary to ask patients to sit far from each other, wear masks while in the waiting room, and wash hands before getting in the dental chair to decrease disease transmission. CONCLUSIONS: Jordanian dentists were aware of COVID-19 symptoms, mode of transmission, and infection controls and measures in dental clinics. However, dentists had limited comprehension of the extra precautionary measures that protect the dental staff and other patients from COVID-19. National and international guidelines should be sent by the regional and national dental associations to all registered dentists during a crisis, including the COVID-19 pandemic, to make sure that dentists are well informed and aware of best practices and recommended disease management approaches.", "qid": 18, "docid": "lh3x6wat", "rank": 33, "score": 8.044499397277832}, {"content": "Title: Deep learning to estimate the physical proportion of infected region of lung for COVID-19 pneumonia with CT image set Content: Utilizing computed tomography (CT) images to quickly estimate the severity of cases with COVID-19 is one of the most straightforward and efficacious methods. Two tasks were studied in this present paper. One was to segment the mask of intact lung in case of pneumonia. Another was to generate the masks of regions infected by COVID-19. The masks of these two parts of images then were converted to corresponding volumes to calculate the physical proportion of infected region of lung. A total of 129 CT image set were herein collected and studied. The intrinsic Hounsfiled value of CT images was firstly utilized to generate the initial dirty version of labeled masks both for intact lung and infected regions. Then, the samples were carefully adjusted and improved by two professional radiologists to generate the final training set and test benchmark. Two deep learning models were evaluated: UNet and 2.5D UNet. For the segment of infected regions, a deep learning based classifier was followed to remove unrelated blur-edged regions that were wrongly segmented out such as air tube and blood vessel tissue etc. For the segmented masks of intact lung and infected regions, the best method could achieve 0.972 and 0.757 measure in mean Dice similarity coefficient on our test benchmark. As the overall proportion of infected region of lung, the final result showed 0.961 (Pearson's correlation coefficient) and 11.7% (mean absolute percent error). The instant proportion of infected regions of lung could be used as a visual evidence to assist clinical physician to determine the severity of the case. Furthermore, a quantified report of infected regions can help predict the prognosis for COVID-19 cases which were scanned periodically within the treatment cycle.", "qid": 18, "docid": "p3t6dsfd", "rank": 34, "score": 8.034500122070312}, {"content": "Title: COVID\u201019: Face masks and human\u2010to\u2010human transmission Content: In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections\uff0cit may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.", "qid": 18, "docid": "wni08lks", "rank": 35, "score": 8.03219985961914}, {"content": "Title: Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19 Content: OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.", "qid": 18, "docid": "9uxfxry4", "rank": 36, "score": 8.010700225830078}, {"content": "Title: Clinician perceptions of respiratory infection risk; a rationale for research into mask use in routine practice Content: Abstract Outbreaks of emerging and re-emerging infectious diseases are global threats to society. Planning for, and responses to, such events must include healthcare and other measures based on current evidence. An important area of infection prevention and control (IPC) is the optimal use of personal protective equipment (PPE) by healthcare workers (HCWs), including masks for protection against respiratory pathogens. Appropriate mask use during routine care is a forerunner to best practice in the event of an outbreak. However, little is known about the influences on decisions and behaviours of HCWs with respect to protective mask use when providing routine care. In this paper we argue that there is a need for more research to provide a better understanding of the decision-making and risk-taking behaviours of HCWs in respect of their use of masks for infectious disease prevention. Our argument is based on the ongoing threat of emerging infectious diseases; a need to strengthen workforce capability, capacity and education; the financial costs of healthcare and outbreaks; and the importance of social responsibility and supportive legislation in planning for global security. Future research should examine HCWs' practices and constructs of risk to provide new information to inform policy and pandemic planning.", "qid": 18, "docid": "kvv3fx2n", "rank": 37, "score": 7.997300148010254}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.", "qid": 18, "docid": "j0lpy07l", "rank": 38, "score": 7.9558000564575195}, {"content": "Title: The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence Content: Please cite this paper as: bin\u2010Reza et al. (2012) The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence. Influenza and Other Respiratory Viruses 6(4), 257\u2013267. There are limited data on the use of masks and respirators to reduce transmission of influenza. A systematic review was undertaken to help inform pandemic influenza guidance in the United Kingdom. The initial review was performed in November 2009 and updated in June 2010 and January 2011. Inclusion criteria included randomised controlled trials and quasi\u2010experimental and observational studies of humans published in English with an outcome of laboratory\u2010confirmed or clinically\u2010diagnosed influenza and other viral respiratory infections. There were 17 eligible studies. Six of eight randomised controlled trials found no significant differences between control and intervention groups (masks with or without hand hygiene; N95/P2 respirators). One household trial found that mask wearing coupled with hand sanitiser use reduced secondary transmission of upper respiratory infection/influenza\u2010like illness/laboratory\u2010confirmed influenza compared with education; hand sanitiser alone resulted in no reduction. One hospital\u2010based trial found a lower rate of clinical respiratory illness associated with non\u2010fit\u2010tested N95 respirator use compared with medical masks. Eight of nine retrospective observational studies found that mask and/or respirator use was independently associated with a reduced risk of severe acute respiratory syndrome (SARS). Findings, however, may not be applicable to influenza and many studies were suboptimal. None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection. Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially hand hygiene. The effectiveness of masks and respirators is likely linked to early, consistent and correct usage.", "qid": 18, "docid": "y43prnko", "rank": 39, "score": 7.950300216674805}, {"content": "Title: The COVID-19 pandemic, personal protective equipment and respirator: A narrative review Content: INTRODUCTION: The coronavirus disease 2019 pandemic has touched almost every continent. Personal protective equipment (PPE) is the final line of protection of healthcare workers (HCW). There is variation as well as controversy of infection control recommendation with regards to the use of PPE for HCW between institutions. The aim of this narrative review is to of examine and summarise the available evidence to guide recommendation for the safety of HCW. METHOD: A literature search was conducted on the PubMed, MedLine and Embase databases with the keywords \"personal protective equipment,\" \"COVID 19,\" \"n95,\" \"health care worker\" and \"mortality.\" RESULTS: SARS-nCoV-2 is highly contagious. About 3.5%-20% of HCW has been reported to be infected. The mortality ranges from 0.53% to 1.94%. PPE is part of the measure within a package of prevention and control of pandemic, rather than a replacement of. Respirators are more effective than masks in preventing aerosol transmission to HCWs. Extended use may be considered if guidelines are adhered. Powered air-purifying respirators if available should be used in high-risk procedures. CONCLUSION: Transmission of viruses is multimodal and in the setting of a novel pathogen with high case fatality with no proven effective interventions, PPE that affords the best protection should be available to HCWs.", "qid": 18, "docid": "dwawjone", "rank": 40, "score": 7.938000202178955}, {"content": "Title: Correspondence: Angiotensin-converting enzyme 2 coated nanoparticles containing respiratory masks, chewing gums and nasal filters may be used for protection against COVID-19 infection Content: \u2022 World has encountered a novel pandemic called as COVID-19. \u2022 All people need protective items such as masks and gloves worldwide. \u2022 Preventing COVID-19 infection has become the most important issue. \u2022 ACE2 containing nanomaterials may be used in the respiratory masks, gloves and clothes. \u2022 Using nanotechnology to prevent this pandemic may be hope for fighting against COVID-19.", "qid": 18, "docid": "g477u9k1", "rank": 41, "score": 7.92549991607666}, {"content": "Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "qid": 18, "docid": "uc37poce", "rank": 42, "score": 7.900700092315674}, {"content": "Title: Application of refined management in the prevention and control of coronavirus disease 2019 epidemic in non-isolated areas of a general hospital Content: Objective: This article summarizes the experience in the prevention and control of coronavirus disease 2019(COVID-19) epidemic in non-isolated areas in a general hospital. Methods: Based on refined management theory, we professionally developed the standards for prevention and control of COVID-19 in non-isolated areas, systematically implemented various prevention and control measures, performed gridding audit, effectively communicated among teams and between doctors and patients assisted by information techniques, and reported results for quality improvement. Results: There was no hospital acquired COVID-19 infections among staff in the hospital. The rates of mask wearing, epidemiological history screening and the medical supplies disinfection were all 100% in the hospital. The accuracy rate of mask wearing of patients and their families was 73.79% and the compliance of their hand hygiene was 40.78%. Conclusion: Refined management strategies for the prevention and control of COVID-19 infection in non-isolated areas of the general hospital are effective. The accuracy rate of mask wearing and hand hygiene compliance of patients and their families need to be further improved.", "qid": 18, "docid": "dpiiaxxt", "rank": 43, "score": 7.890999794006348}, {"content": "Title: Application of refined management in prevention and control of the coronavirus disease 2019 epidemic in non-isolated areas of a general hospital Content: Abstract Objective This article summarizes the experience in the prevention and control of coronavirus disease 2019(COVID-19) epidemic in non-isolated areas in a general hospital. Methods Based on refined management theory, we professionally developed the standards for prevention and control of COVID-19 in non-isolated areas, systematically implemented various prevention and control measures, performed gridding audits, effectively communicated among teams and between medical staff and patients assisted by information techniques, and reported results for quality improvement. Results There was no hospital-acquired COVID-19 infections among staff in the hospital. The rates of mask-wearing, epidemiological history screening, and the medical supplies disinfection were all 100% in the hospital. The accuracy rate of mask-wearing of patients and their families was 73.79% and the compliance rate of their hand hygiene was 40.78%. Conclusion Refined management strategies for the prevention and control of COVID-19 infection in non-isolated areas of the general hospital are effective. The accuracy rate of mask-wearing and hand hygiene compliance of patients and their families need to be further improved.", "qid": 18, "docid": "i8w88cb0", "rank": 44, "score": 7.890998840332031}, {"content": "Title: Analysis of national and international guidelines on respiratory protection equipment for COVID-19 in healthcare settings. Content: Introduction Consistent guidelines on respiratory protection for healthcare professionals combined with improved global supply chains are critical to protect staff and patients from COVID-19. We summarized and compared the guidelines published by national and international societies/organizations on facemasks and respirators to prevent COVID-19 in healthcare settings. Methods From the 1st January to the 2nd April 2020, guidelines published in four countries (France, Germany, United States, United Kingdom), and two international organizations (US and European Center for Diseases Control, and World Health Organization) were reviewed to analyze the mask and respirators recommended as PPE for the care of patients during the COVID-19 outbreak. Guidelines were eligible for analysis if they (1) included specific guidelines, (2) were written for HCP protection, (3) targeting healthcare settings. The strategy recommended for optimizing supplies and overcoming shortages was collected. Observations The guidelines publication process on respiratory protections varied greatly across countries. Some referred to a unique guide whereas others saw the issue of multiple recommendations by various societies and organization. In term of chronology, most guidelines were published in March with either downgraded (US and European CDC), relatively stable (WHO, Germany, and UK), or a mixing of high and low level equipment (France). The recommendation of respirators was universally recommended for aerosol generating procedures (AGP) across countries, although the type of respirators and what constituted an AGP was variable. Some guidance maintained the use of N95/99 for all contact with confirmed COVID-19 cases (i.e. Germany) whereas others, recommended a surgical mask (i.e. WHO, UK, France). The strategies to overcome shortage of respiratory protection equipment were based on minimizing the need and rationalizing the use, but also prolonging their use, reusing them after cleaning/sterilization, or using cloth masks. Conclusions Stable and consistent guidelines inside and across countries, clearly detailing the respiratory protection type, and the circumstances in which they need to be used may prevent the confusion among frontline staff, and avoid shortage.", "qid": 18, "docid": "wahcfox7", "rank": 45, "score": 7.882199764251709}, {"content": "Title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines Content: Summary In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.", "qid": 18, "docid": "4mx9t5td", "rank": 46, "score": 7.870100021362305}, {"content": "Title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines Content: In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.", "qid": 18, "docid": "ndy59p5p", "rank": 47, "score": 7.870099067687988}, {"content": "Title: Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis Content: OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on \u2018PubMed\u2019 and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral\u2013fecal or fecal\u2013droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.", "qid": 18, "docid": "idlyl4ga", "rank": 48, "score": 7.852799892425537}, {"content": "Title: Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis Content: OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on 'PubMed' and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral-fecal or fecal-droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.", "qid": 18, "docid": "o6a4kmmh", "rank": 49, "score": 7.852798938751221}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 18, "docid": "6wxjm7m0", "rank": 50, "score": 7.826499938964844}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 18, "docid": "r1oqwdkz", "rank": 51, "score": 7.785699844360352}, {"content": "Title: Coronavirus infection prevention by wearing masks Content: The coronavirus disease 2019 (COVID-19) [2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] was first detected in Wuhan, China at the end of 2019. In current status, spread of CO-VID-19 in person-to-person could be caused mainly by respiratory droplets, which leads to the spread of the influenza virus in both community and clinicians. Thus, in order to reduce the risk of that, the urgent management strategies against COVID-19 are to block transmission, isolation, protection, and using drug or vaccine updated on an ongoing basis. unfortunately, no drugs or vaccines still has yet been allowed to treat patients with COVID-19, so the rapid detection of effective intercessions against COVID-19 is seemed a major challenge on the all world. Herein, this article attempts summarizing to introduce the characterization of COVID-19, the influence of droplets travel in person-to-person transmission and the effect of wearing masks in the infection prevention of influenza virus, as well as understanding its advantage and role in the coronavirus infection prevention.", "qid": 18, "docid": "q0ey3wib", "rank": 52, "score": 7.591400146484375}, {"content": "Title: Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks Content: Summary Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organisation state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected severe acute respiratory syndrome (SARS). In areas where N95 masks are not available, multiple layers of surgical masks have been tried to prevent transmission of SARS. The in vivo filtration capacity of a single surgical mask is known to be poor. However, the filtration capacity of a combination of masks is unknown. This was a crossover trial of one, two, three and five surgical masks in six volunteers to determine the in vivo filtration efficiency of wearing more than one surgical mask. We used a Portacount to measure the difference in ambient particle counts inside and outside the masks. The best combination of five surgical masks scored a fit factor of 13.7, which is well below the minimum level of 100 required for a half face respirator. Multiple surgical masks filter ambient particles poorly. They should not be used as a substitute for N95 masks unless there is no alternative.", "qid": 18, "docid": "wzmfmcpt", "rank": 53, "score": 7.583700180053711}, {"content": "Title: Anosmia: a COVID-19 symptom that must be investigated by rhinoplasty surgeons Content: the prevention of the COVID-19 epidemic between the LTCFs having been contaminated by at least one case of COVID-19 among residents and/or LTCFs staff and LTCFs with no cases of COVID between March 23rd and May 6th, in the year 2020 Methods Participants The epidemic risk being variable over time and from one region to another, and because the guidance have evolved over time in short-term periods, our study was limited to all the LTCFs of the Haute-Garonne department (Occitania region), SouthWestern France, between March 23rd and May 6th, 2020 We sent a questionnaire to LTCFs directors/medical staff by email on March 30th, to all the 132 LTCFs registered in the Haute-Garonne department After sending the questionnaire, we systematically performed a phone call (period of 6 to 19 May 2020) to the LTCFs either coordinating nurse or coordinating doctor in order to explain the questions and guide them on how to complete the questionnaire online The questionnaire focused on the preventive measures implemented in the LTCF before March 23rd, 2020 This date refers to the first confirmed case of COVID-19 in LTCFs in the department of Haute Garonne At that period, none of the other LTCFs had confirmed cases of COVID-19 The questionnaire therefore relates to practices at the time that preceded the arrival of the epidemic wave This date was also chosen because it was, on the basis of our field knowledge (7), an important motivational element for local LTCFs to implement more strictly all the guidance for LTCFs This event was indeed widely diffused in the media in the Haute Garonne department, in the official website of the association of LTCFs coordinating doctors and allowed a temporal reference of a major local event helping LTCFs staff to complete the questionnaire accurately Variables of interest The questionnaire included the status of the LTC (public, private for-profit, private non-profit) and the presence of a coordinating physician (yes/no) The implementation of the guidance were listed (each recommendation was a dichotomy: yes/no) regarding: the systematic wearing of masks by the healthcare professional;access to effective masks (surgical and/or FFP2);satisfactory supply of masks;satisfactory supply of hydro-alcoholic solute;access to specific internal or external training on hygiene measures throughout the year;the use of containment in residents' rooms;during meals, separating residents to each other, respecting a distance of at least one meter (in the dining room with distance, in small groups, in bedroom);cessation of group activities for residents (with distance, in small groups);the use of interim jobs;staff compartmentalization within zones (organization of the work so that the team works in small groups in one area of the LTCF with no physical connection with the other members of the team);resident compartmentalization within zones (organization of the LTCF so that the resident live in small groups in one area of the LTCF with no possible physical connection with the other residents);specific dressing procedure at the entrance (complete daily routine dress change at the entrance and exit of the LTCF for anyone entering the LTCF) In order to judge the global prevention effort made by the healthcare team, the questionnaire ended with a self-assessment scale: To what extent do you think the nursing home staff has satisfactorily applied all the recommended \u00abbarrier\u00bb measures? (rated from 0, not at all, to 10, perfectly) At the end of the phone call, the coordinating nurse or coordinating doctor was asked to give a global judgment of the follow-up of the guidance by the all nursing home staff Outcome measure The coordinating nurse or doctor should specify whether, in the LTCFs, one or more residents and/or one or more caregivers were infected with COVID-19 (yes/no) The cases had to be confirmed by a positive rt-PCR test Unity of measurement was the LTCF Ethics This study is a survey of the leaders of the LTCFs and no data relating to residents was collected The approval of the ethics c mmittee was not required Statistical Analysis Qualitative variables are described as numbers and percentage [n (%)] and quantitative variables as mean and standard deviation (SD) Bivariate analysis used the chi-square test (Fisher's exact test if applicable) and the Student's ttest for independent samples, as appropriate In order to consider the confounding factors, a logistic regression was realized Multicollinearity was assessed The initial model was composed of variables found associated with a LTCFs infected by COVID-19 to a threshold of 0 20 in bivariate analysis Then, a reduced model was performed, using a step by step backward regression Analysis has been duplicated separately for private and public LTCFs Results Among the 132 LTCFs in the region, 124 (93 9%) agreed to participate and 8 refused In 30 LTCFs, confirmed cases of COVID-19 (24 2%) were found among: one or more residents (n = 6 LTCFs), one or more caregivers (n = 17), or both (n = 7) Seven LTCFs (5 6%) had confirmed cases for two or more residents Table 1 shows the implementation of guidance in the LTCFs with confirmed COVID cases vs those without confirmed cases In bivariate analyses, LTCFs ownership, staff compartmentalization within zones, use of professional interim, and organization of the meals with \u2265 1-meter distance separating residents to each other were significantly associated with infection of COVID-19 in the LTCFs The", "qid": 18, "docid": "i1gdsiw6", "rank": 54, "score": 7.566400051116943}, {"content": "Title: Coproducing Responses to COVID\u201019 with Community\u2010Based Organizations: Lessons from Zhejiang Province, China Content: Zhejiang Province achieved one of the best records in containing the COVID\u201019 pandemic in China, what lessons can the world learn from it? What roles do community\u2010based organizations play in its success story? Based on more than 100 interviews during and after the outbreak in Zhejiang, this article provides a roadmap of how community\u2010based organizations were involved in the three distinct stages of Zhejiang's responses to COVID\u201019. We recommend that public sector leaders strategically leverage the strengths of community\u2010based organizations in multiple stages of COVID\u201019 responses; incentivize volunteers to participate in epidemic prevention and control; provide data infrastructure and digital tracking platforms; and build trust and long\u2010term capacity of community\u2010based organizations. This article is protected by copyright. All rights reserved.", "qid": 18, "docid": "9v0z2chz", "rank": 55, "score": 7.561800003051758}, {"content": "Title: Social and behavioral health responses to COVID-19: lessons learned from four decades of an HIV pandemic Content: Our public health approaches to addressing COVID-19 are heavily dependent on social and behavioral change strategies to halt transmissions. To date, biomedical forms of curative and preventative treatments for COVID-19 are at best limited. Four decades into the HIV epidemic we have learned a considerable amount of information regarding social and behavioral approaches to addressing disease transmission. Here we outline broad, scoping lessons learned from the HIV literature tailored to the nature of what we currently know about COVID-19. We focus on multiple levels of intervention including intrapersonal, interpersonal, community, and social factors, each of which provide a reference point for understanding and elaborating on social/behavioral lessons learned from HIV prevention and treatment research. The investments in HIV prevention and treatment research far outweigh any infectious disease in the history of public health, that is, until now with the emergence of COVID-19.", "qid": 18, "docid": "dbhfnvi2", "rank": 56, "score": 7.53410005569458}, {"content": "Title: Let food be the medicine, but not for coronavirus: Nutrition and food science, telling myths from facts Content: The entire globe is facing a dangerous pandemic due to the coronavirus disease (COVID-19). The medical and scientific community is trying to figure out and adopt effective strategies that can lead to (i) preventing virus expansion; (ii) identifying medications for the management of critical care and reducing rates of mortality; and (iii) finally discovering the highly anticipated vaccine. Nutritional interventions have attained considerable scientific evidence in disease prevention and treatment. The main question, \u201cWhat is the role of nutrition and food science in this scenario?\u201d requires urgent answer as many theories suggesting that specific food or dietary supplements can fight coronavirus infection have received extensive coverage in most popular social media platforms. In this editorial, we focus on some frequent statements on the role of nutrition and food science in the battle against COVID-19, distinguishing between myths and facts. We highlight that social distancing and hygiene precautions are the best practices for reducing the risk of COVID-19 transmission. We further underline the importance of nutrition in its wholistic concept, pointing out the risk of unproven dietary options that could lead individuals to weaken effective precautionary measures.", "qid": 18, "docid": "3mcl83nz", "rank": 57, "score": 7.5295000076293945}, {"content": "Title: Medical masks vs N95 respirators for preventing COVID\u201019 in healthcare workers: A systematic review and meta\u2010analysis of randomized trials Content: BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID\u201019); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID\u201019 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory\u2010confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta\u2010analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory\u2010confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90\u20101.25; I (2) = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98\u20102.28; I (2) = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non\u2013aerosol\u2010generating care. Preservation of N95 respirators for high\u2010risk, aerosol\u2010generating procedures in this pandemic should be considered when in short supply.", "qid": 18, "docid": "1aqf98e0", "rank": 58, "score": 7.478499889373779}, {"content": "Title: Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials Content: BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID-19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID-19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory-confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta-analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory-confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90-1.25; I2 = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98-2.28; I2 = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non-aerosol-generating care. Preservation of N95 respirators for high-risk, aerosol-generating procedures in this pandemic should be considered when in short supply.", "qid": 18, "docid": "8khrecrf", "rank": 59, "score": 7.478498935699463}, {"content": "Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "qid": 18, "docid": "ugkxxaeb", "rank": 60, "score": 7.471099853515625}, {"content": "Title: The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review. Content: Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "qid": 18, "docid": "f7rcijh4", "rank": 61, "score": 7.467299938201904}, {"content": "Title: Does Collective Interest or Self-Interest Motivate Mask Usage as a Preventive Measure Against COVID-19? Content: The revised guidance on masks from public health officials has been one of the most significant COVID-19 policy reversals to date. Statements made at the outset of the pandemic, including those from the World Health Organization (WHO), the United States Surgeon General, and the Chief Public Health Officer of Canada, all actively discouraged asymptomatic members of the general public from wearing masks. However, on April 3, 2020, the United States Center for Disease Control and Prevention (CDC) issued new recommendations that called for nonmedical masks, such as cloth face coverings, to be worn in public settings where other social distancing measures are difficult to maintain (Adams, 2020). Canadian public health officials quickly followed with their own guidance for wearing nonmedical masks or face coverings when out in public; however, they have stressed that doing so is optional for asymptomatic persons and should be seen as a complement to existing precautionary measures such as physical distancing and hand hygiene, particularly in cases where physical distancing may not be feasible (Public Health Agency of Canada, 2020). Emphasis was placed on nonmedical masks serving not to protect the wearer, but rather others who come within close proximity of the wearer. Echoing her public statements on the matter, Canada's chief public health officer Tweeted that \u201c[w]earing a NON-MEDICAL mask in public settings has not been proven to add any protection TO the person wearing it, but it can be an additional way to prevent spread FROM an infected person to others\u201d (Tam, 2020).", "qid": 18, "docid": "pynqwj5t", "rank": 62, "score": 7.467298984527588}, {"content": "Title: Universal masking in hospitals in the COVID-19 era: Is it time to consider shielding? Content: With concerns for presymptomatic transmission of COVID-19 and increasing burden of contact tracing and employee furloughs, several hospitals have supplemented pre-existing infection prevention measures with universal masking of all personnel in hospitals. Other hospitals are currently faced with the dilemma of whether or not to proceed with universal masking in a time of critical mask shortages. We summarize the rationale behind a universal masking policy in healthcare settings, important considerations before implementing such a policy and the challenges with universal masking. We also discusses proposed solutions such as universal face shields.", "qid": 18, "docid": "pt3a5y49", "rank": 63, "score": 7.458700180053711}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index &#8805;40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 18, "docid": "3jwl97qb", "rank": 64, "score": 7.416100025177002}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy. Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index \u226540), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 18, "docid": "7ofa04l1", "rank": 65, "score": 7.4160990715026855}, {"content": "Title: Skull-base surgery during the COVID-19 pandemic: the Italian Skull Base Society recommendations Content: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment (PPE) is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combating the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was 1 of the earliest and hardest-hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, filtering facepiece 3 (FFP3) and/or powered air purifying respirator (PAPR) devices, goggles, full-face visor, double gloves, water-resistant gowns, and protective caps are mandatory. For negative patients, use of at least an FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS-CoV-2, dura handling should be minimized. It is only through widely-agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic.", "qid": 18, "docid": "0sk0o04v", "rank": 66, "score": 7.405200004577637}, {"content": "Title: Skull base surgery during the Covid\u201019 pandemic: The Italian skull base society recommendations Content: Severe acute respiratory syndrome\u2010coronavirus\u20102 (SARS\u2010CoV\u20102), which causes coronavirus disease 2019 (Covid\u201019), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combatting the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was one of the earliest and hardest\u2010hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, FFP3 and/or PAPRs devices, goggles, full\u2010face visor, double gloves, water\u2010resistant gowns and protective caps, are mandatory. For negative patients, use of at least FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS\u2010CoV\u20102, dura handling should be minimized. It is only through widely\u2010agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic. This article is protected by copyright. All rights reserved", "qid": 18, "docid": "yhjoaw9m", "rank": 67, "score": 7.40519905090332}, {"content": "Title: COVID-19: Special Precautions in Ophthalmic Practice and FAQs on Personal Protection and Mask Selection Content: The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory coronavirus-2, was first reported in December 2019. The World Health Organization declared COVID-19 a pandemic on March 11, 2020 and as of April 17, 2020, 210 countries are affected with >2,000,000 infected and 140,000 deaths. The estimated case fatality rate is around 6.7%. We need to step up our infection control measures immediately or else it may be too late to contain or control the spread of COVID-19. In case of local outbreaks, the risk of infection to healthcare workers and patients is high. Ophthalmic practice carries some unique risks and therefore high vigilance and special precautions are needed. We share our protocols and experiences in the prevention of infection in the current COVID-19 outbreak and the previous severe acute respiratory syndrome epidemic in Hong Kong. We also endeavor to answer the key frequently asked questions in areas of the coronaviruses, COVID-19, disease transmission, personal protection, mask selection, and special measures in ophthalmic practices. COVID-19 is highly infectious and could be life-threatening. Using our protocol and measures, we have achieved zero infection in our ophthalmic practices in Hong Kong and China. Preventing spread of COVID-19 is possible and achievable.", "qid": 18, "docid": "zxl84e2m", "rank": 68, "score": 7.40310001373291}, {"content": "Title: Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2 Content: Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "qid": 18, "docid": "tcijnphu", "rank": 69, "score": 7.381499767303467}, {"content": "Title: Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2. Content: Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "qid": 18, "docid": "xtraspw2", "rank": 70, "score": 7.38149881362915}, {"content": "Title: Selection of homemade mask materials for preventing transmission of COVID-19: a laboratory study Content: The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the \"Surgical Mask\" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference ([\u2264]49 Pa), of which 3 met the standard of resistance to surface wetting ([\u2265]3), 1 met the standard of particle filtration efficiency ([\u2265]30%), but none met the standard of bacterial filtration efficiency ([\u2265]95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.", "qid": 18, "docid": "o5esfwf4", "rank": 71, "score": 7.3813982009887695}, {"content": "Title: Event-specific interventions to minimize COVID-19 transmission Content: Coronavirus disease 2019 (COVID-19) is a global pandemic with over 11 million cases worldwide. Currently there is no treatment and no vaccine. Interventions such as hand washing, masks, social distancing, and \"social bubbles\" are used to limit community transmission, but it is challenging to choose the best interventions for a given activity. Here, we provide a quantitative framework to determine which interventions are likely to have the most impact in which settings. We introduce the concept of \"event R\", the expected number of new infections due to the presence of a single infected individual at an event. We obtain a fundamental relationship between event R and four parameters: transmission intensity, duration of exposure, the proximity of individuals, and the degree of mixing. We use reports of small outbreaks to establish event R and transmission intensity in a range of settings. We identify principles that guide whether physical distancing, masks and other barriers to transmission, or social bubbles will be most effective. We outline how this information can be obtained and used to re-open economies with principled measures to reduce COVID-19 transmission.", "qid": 18, "docid": "u34301eg", "rank": 72, "score": 7.380799770355225}, {"content": "Title: Best practice recommendations: ENT consultations during the COVID-19 pandemic Content: These best practice recommendations for ENT consultations during the COVID-19 pandemic have been drawn up because ENT examinations and treatments are at risk of contamination by the SARS-Cov-2 virus in certain instances. Thus, ENT specialists are among the professionals who are most exposed to this infection. During the pandemic, insofar as an asymptomatic patient may be infected and contagious, the same precautions must be employed whether the patient is ill with, suspected of having, or without any clinical evidence of COVID-19 infection. According to the scientific data available, the examinations and procedures potentially exposing to projections/aerosolizations of organic material of human origin are considered to be at risk of staff contamination. For ENT examinations and procedures without exposure to such projections/aerosolizations, the professional is advised to a long sleeve clean outfit, a surgical mask and gloves in case of contact with the patient's mucosa. ENT examinations and procedures with exposure to these projections/aerosolizations require the so-called \"airborne\", \"contact\", and \"droplets\" additional precautions: FFP2/N95 respiratory protection device, eye protection, disposable headwear and long sleeve overgown.", "qid": 18, "docid": "5vz98lr4", "rank": 73, "score": 7.369100093841553}, {"content": "Title: Best practice recommendations: ENT consultations during the COVID-19 pandemic Content: These best practice recommendations for ENT consultations during the COVID-19 pandemic have been drawn up because ENT examinations and treatments are at risk of contamination by the SARS-Cov-2 virus in certain instances. Thus, ENT specialists are among the professionals who are most exposed to this infection. During the pandemic, insofar as an asymptomatic patient may be infected and contagious, the same precautions must be employed whether the patient is ill with, suspected of having, or without any clinical evidence of COVID-19 infection. According to the scientific data available, the examinations and procedures potentially exposing to projections/aerosolizations of organic material of human origin are considered to be at risk of staff contamination. For ENT examinations and procedures without exposure to such projections/aerosolizations, the professional is advised to a long sleeve clean outfit, a surgical mask and gloves in case of contact with the patient's mucosa. ENT examinations and procedures with exposure to these projections/aerosolizations require the so-called \u201cairborne\u201d, \u201ccontact\u201d, and \u201cdroplets\u201d additional precautions: FFP2/N95 respiratory protection device, eye protection, disposable headwear and long sleeve overgown.", "qid": 18, "docid": "qw4az7dd", "rank": 74, "score": 7.369099140167236}, {"content": "Title: COVID-19 and myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimising risk of contracting coronavirus disease 2019 (COVID-19) and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post-pandemic environment, the treatment delivered to patients could be more cost-effective and better tailored than before. Healthcare delivery post-COVID-19 will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 18, "docid": "sexx9196", "rank": 75, "score": 7.360899925231934}, {"content": "Title: Covid\u201019 and Myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimizing risk of contracting COVID\u201019 and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post\u2010pandemic environment, the treatment delivered to patients could be more cost effective and better tailored than before. Healthcare delivery post\u2010COVID will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 18, "docid": "njg0ln33", "rank": 76, "score": 7.31790018081665}, {"content": "Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "qid": 18, "docid": "5zb96j4a", "rank": 77, "score": 7.310999870300293}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17--45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34--58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24--65% (and peak deaths 15--69%), compared to 2--9% mortality reduction in New York (peak death reduction 9--18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 18, "docid": "28utunid", "rank": 78, "score": 7.301799774169922}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17\u201345% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34\u201358%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24\u201365% (and peak deaths 15\u201369%), compared to 2\u20139% mortality reduction in New York (peak death reduction 9\u201318%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 18, "docid": "qi1henyy", "rank": 79, "score": 7.3017988204956055}, {"content": "Title: Surgical mask partition reduces the risk of non-contact transmission in a golden Syrian hamster model for Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium-to-large sized respiratory droplets although airborne transmission is theoretically possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. METHODS: We used a well-established golden Syrian hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index hamsters and na\u00efve hamsters into closed system units each comprising two different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed in between the cages was investigated. Besides clinical scoring, hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. RESULTS: Non-contact transmission was found in 66.7% (10/15) of exposed na\u00efve hamsters. Surgical mask partition for challenged index or na\u00efve hamsters significantly reduced transmission to 25% (6/24, P=0.018). Surgical mask partition for challenged index hamsters significantly reduced transmission to only 16.7% (2/12, P=0.019) of exposed na\u00efve hamsters. Unlike the severe COVID-19 manifestations of challenged hamsters, infected na\u00efve hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. CONCLUSIONS: SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei in the hamster model. Such transmission could be reduced by surgical mask usage, especially when masks were worn by infected individuals.", "qid": 18, "docid": "i5i8hb80", "rank": 80, "score": 7.291999816894531}, {"content": "Title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China Content: There is currently a global outbreak of coronavirus disease 2019 (COVID-19), and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported.Describe the epidemic characteristics of COVID-19 in Jingmen, Hubei, introduce the local prevention and control experience, and observe the impact of various prevention and control measures on the number of new cases.All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29, 2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic.Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range, 2-88 years; IQR, 35-60). Thirty-three severe patients with a median age of 66 years (range, 33-82 years, IQR, 57-76) were treated in intensive care units; out of these patients, 66.7% (22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures.In conclusion, all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious, control measures have proven to be very effective, particularly wearing masks, which could prevent most infections.", "qid": 18, "docid": "ei0lagpp", "rank": 81, "score": 7.291100025177002}, {"content": "Title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China Content: There is currently a global outbreak of coronavirus disease 2019 (COVID-19), and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported. Describe the epidemic characteristics of COVID-19 in Jingmen, Hubei, introduce the local prevention and control experience, and observe the impact of various prevention and control measures on the number of new cases. All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29, 2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic. Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range, 2\u201388 years; IQR, 35\u201360). Thirty-three severe patients with a median age of 66 years (range, 33\u201382 years, IQR, 57\u201376) were treated in intensive care units; out of these patients, 66.7% (22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures. In conclusion, all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious, control measures have proven to be very effective, particularly wearing masks, which could prevent most infections.", "qid": 18, "docid": "kbxlo7pu", "rank": 82, "score": 7.2910990715026855}, {"content": "Title: Epidemiology reveals mask wearing by the public is crucial for COVID-19 control Content: Abstract Objective The pandemic 2019 Coronavirus disease (COVID-19) is the greatest concern globally. Here we analyzed the epidemiological features of China, South Korea, Italy and Spain to find out the relationship of major public health events and epidemiological curves. Study design In this study we describe and analyze the epidemiological characteristics of COVID-19 in and outside China. We use GAM to generate the epidemiological curves and simulate infection curves with reported incubation period. Results The epidemiological curved derived from the GAM suggested that the infection curve can reflect the public health measurements sensitively. Under the massive actions token in China, the infection curve flattened at 23rd of January. While surprisingly, even before Wuhan lockdown and first level response of public emergency in Guangdong and Shanghai, those infection curve came to the reflection point both at 21st of January, which indicated the mask wearing by the public before 21st Jan were the key measure to cut off the transmission. In the countries outside China, infection curve also changed in response to measures, but its rate of decline was much smaller than the curve of China's. Conclusion The present analysis comparing the epidemiological curves in China, South Korea, Italy and Spain supports the importance of mask wearing by the public. Analysis of the infection curve helped to clarify the impact of important public health events, evaluate the efficiencies of prevention measures, and showed wearing masks in public resulted in significantly reduced daily infected cases.", "qid": 18, "docid": "fsis95hd", "rank": 83, "score": 7.2631001472473145}, {"content": "Title: Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission Content: Summary The world is facing a pandemic of unseen proportions caused by a corona virus named SARS-CoV-2 with unprecedent worldwide measures being taken to tackle its contagion. Person-to-person transmission is accepted but WHO only considers aerosol transmission when procedures or support treatments that produce aerosol are performed. However, transmission mechanisms are not fully understood and there is evidence for an airborne route to be considered as the virus remains viable in aerosols for at least 3h and that mask usage was the best intervention to prevent infection. Heating, Ventilating and Air Conditioning Systems (HVAC) are used as a primary infection disease control measure. However, they may contribute to the transmission/spreading of airborne diseases as proposed in the past for SARS. The authors believe that airborne transmission is possible and that HVAC systems when not adequately used may contribute to the transmission of the virus, as suggested by descriptions of from Japan, Germany, and the Diamond Princess Cruise Ship. Previous SARS outbreaks reported at Amoy Gardens, Emergency Rooms and Hotels, for example, also suggested airborne transmission. Further studies are warranted to confirm our hypotheses but the assumption of such way of transmission would cause a major shift in measures recommended to prevent infection such as the disseminated use of masks and structural changes to hospital and other facilities HVAC systems.", "qid": 18, "docid": "3q3sktuq", "rank": 84, "score": 7.262599945068359}, {"content": "Title: Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission Content: The world is facing a pandemic of unseen proportions caused by a corona virus named SARS-CoV-2 with unprecedent worldwide measures being taken to tackle its contagion. Person-to-person transmission is accepted but WHO only considers aerosol transmission when procedures or support treatments that produce aerosol are performed. Transmission mechanisms are not fully understood and there is evidence for an airborne route to be considered, as the virus remains viable in aerosols for at least 3 h and that mask usage was the best intervention to prevent infection. Heating, Ventilation and Air Conditioning Systems (HVAC) are used as a primary infection disease control measure. However, if not correctly used, they may contribute to the transmission/spreading of airborne diseases as proposed in the past for SARS. The authors believe that airborne transmission is possible and that HVAC systems when not adequately used may contribute to the transmission of the virus, as suggested by descriptions from Japan, Germany, and the Diamond Princess Cruise Ship. Previous SARS outbreaks reported at Amoy Gardens, Emergency Rooms and Hotels, also suggested an airborne transmission. Further studies are warranted to confirm our hypotheses but the assumption of such way of transmission would cause a major shift in measures recommended to prevent infection such as the disseminated use of masks and structural changes to hospital and other facilities with HVAC systems.", "qid": 18, "docid": "rqw9jir0", "rank": 85, "score": 7.262598991394043}, {"content": "Title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS Content: ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study \u2013 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 18, "docid": "h7ftu3ax", "rank": 86, "score": 7.222499847412109}, {"content": "Title: A rapid systematic review of the efficacy of face masks and respirators against coronaviruses and other respiratory transmissible viruses for the community, healthcare workers and sick patients Content: BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study - 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be effective with and without hand hygiene, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 18, "docid": "in16u4pm", "rank": 87, "score": 7.222498893737793}, {"content": "Title: What variables can better predict the number of infections and deaths worldwide by SARS-CoV-2? Variation through time Content: Lack of knowledge is the main problem we face in the global Covid-19 pandemic. SARS-CoV-2 is a new virus of which there were no previous studies. Using data from 50 very different countries and by means of a regression analysis, we studied the degree to which a series of variables (health indicators, environmental parameters, economic and social indicators, general characteristics of the country) were able to predict the number of people infected and killed by Covid-19. We also studied how these variables were changing their ability to predict the number of infected and dead by covid-19 during a 3 months period (March, April, May). The number of deaths by Covid-19 can always be predicted with great accuracy from the number of infected, regardless of the characteristics of the country (which has better or worse health, greater or lesser wealth, regardless of its population structure, etc.). Epidemiological measures to prevent transmission, mainly travel and mobility restrictions, proved to be much more efficient than having large hospital and medical resources. Inbound tourism turned out to be the variable that best predicts the number of infected (and, consequently, the number of deaths) happening in the different countries. Electricity consumption and degree of air pollution of a country (CO2 emissions, nitrous oxide and methane) are also capable of predicting, with great precision, the number of infections and deaths from Covid-19 in that country. Characteristics such as the area and population of a country also can predict, although to a lesser extent, the number of infected and dead. In contrast, a series of variables, which in principle would seem to have a greater influence on the evolution of Covid-19 (hospital bed density, Physicians per 1000 people, Researches in R & D, urban population, etc.), turned out to have very little ability to predict both the number of infected and the number of deaths from Covid-19. All this may explain why the countries that opted for social withdrawal policies since the start of the pandemic outbreak obtained better results.", "qid": 18, "docid": "iut1xj7k", "rank": 88, "score": 7.206200122833252}, {"content": "Title: Significant reduction in hospital admissions for acute exacerbation of chronic obstructive pulmonary disease in Hong Kong during coronavirus disease 2019 pandemic Content: BACKGROUND: Chronic respiratory diseases are risk factors for severe disease in coronavirus disease 2019 (COVID-19). Respiratory tract infection is one of the commonest causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There has not been evidence suggesting the link between COVID-19 and AECOPD, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. METHODS: This is a retrospective study to assess the number of admissions of AECOPD in the first three months of 2020 in Queen Mary Hospital with reference to the admissions in past five years. Log-linear model was used for statistical inference of covariates, including percentage of masking, air quality health index and air temperature. RESULTS: The number of admissions for AECOPD significantly decreased by 44.0% (95% CI 36.4%\u201352.8%, p < 0.001) in the first three months of 2020 compared with the monthly average admission in 2015\u20132019. Compare to same period of previous years, AECOPD decreased by 1.0% with each percent of increased masking (p < 0.001) and decreased by 3.0% with increase in 1 \u00b0C in temperature (p = 0.045). The numbers of admissions for control diagnoses (heart failure, intestinal obstruction and iron deficiency anaemia) in the same period in 2020 were not reduced. CONCLUSIONS: The number of admissions for AECOPD decreased in first three months of 2020, compared with previous years. This was observed with increased masking percentage and social distancing in Hong Kong. We postulated universal masking and social distancing during COVID-19 pandemics both contributed in preventing respiratory tract infections hence AECOPD.", "qid": 18, "docid": "cl0q7hrn", "rank": 89, "score": 7.1722002029418945}, {"content": "Title: UNIVERSAL MASKING DURING COVID-19 PANDEMIC - CURRENT EVIDENCE AND CONTROVERSIES. Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 18, "docid": "cvulb9t6", "rank": 90, "score": 7.147200107574463}, {"content": "Title: Universal Masking during Covid-19 Pandemic - Current Evidence and Controversies Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 18, "docid": "fdkqs3rg", "rank": 91, "score": 7.1471991539001465}, {"content": "Title: Healthcare worker mask reuse in a global pandemic: Using idle resources to create an inexpensive, scalable, and accessible UV system for N95 sterilization Content: As the current COVID-19 pandemic illustrates, not all hospitals and other facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Healthcare workers around the world utilize N95 masks to protect themselves and their patients, yet during this global pandemic they are forced to re-wear what is intended to be single-use masks. This poses significant risk to these healthcare workers along with the populations they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a way to effectively sterilize these masks between use, however, not all facilities have access to the high cost commercial UV-C lamp sterilization equipment. However, UV-C bulbs are sitting idle in biosafety cabinets (BSCs) at universities and research facilities around the globe that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. Therefore, we have developed a method to modify existing light fixtures, or create custom light fixtures compatible with new or existing common UV-C bulbs. This system is scalable and can be created for less than 50 US dollars, on site, at the point of need, and leverages resources that are currently untapped and sitting unused in public and private research facilities. The freely-accessible design can be easily modified for use around the world. Hospitals can obtain this potentially life-saving UVGI resource with minimal funds, via collaboration between research facilities to obtain the UV-C meters and limited availability UVGI bulbs. While mask reuse is not ideal, we must do what we can in emergency situations to protect our frontline healthcare workers and the communities they serve.", "qid": 18, "docid": "hddseyd8", "rank": 92, "score": 7.1417999267578125}, {"content": "Title: Medical mask versus cotton mask for preventing respiratory droplet transmission in micro environments Content: Abstract The objective of this study was to investigate whether cotton mask worn by respiratory infection person could suppress respiratory droplet levels compared to medical mask. We recruited adult volunteers with confirmed influenza and suspected cases of coronavirus disease 2019 (COVID-19) to wear medical masks and self-designed triple-layer cotton masks in a regular bedroom and a car with air conditioning. Four 1-hour repeated measurements (two measurements for bedroom the others for car) of particles with a size range of 20\u20131000 nm measured by number concentrations (NC0.02\u20131), temperature and relatively humidity, and cough/sneeze counts per hour were conducted for each volunteer. The paired t-tests were used for within-group comparisons in a bedroom and in a car. The results showed that there was no significant difference in NC0.02\u20131 or cough/sneeze counts between volunteers with medical masks and cotton masks in a bedroom or a car. We concluded that the cotton mask could be a potential substitute for medical mask for respiratory infection person in microenvironment with air conditioning. Healthy people may daily use cotton mask in the community since cotton mask is washable and reusable.", "qid": 18, "docid": "1w0dd54t", "rank": 93, "score": 7.138199806213379}, {"content": "Title: Medical mask versus cotton mask for preventing respiratory droplet transmission in micro environments Content: The objective of this study was to investigate whether cotton mask worn by respiratory infection person could suppress respiratory droplet levels compared to medical mask. We recruited adult volunteers with confirmed influenza and suspected cases of coronavirus disease 2019 (COVID-19) to wear medical masks and self-designed triple-layer cotton masks in a regular bedroom and a car with air conditioning. Four 1-hour repeated measurements (two measurements for bedroom the others for car) of particles with a size range of 20-1000 nm measured by number concentrations (NC0.02-1), temperature and relatively humidity, and cough/sneeze counts per hour were conducted for each volunteer. The paired t-tests were used for within-group comparisons in a bedroom and in a car. The results showed that there was no significant difference in NC0.02-1 or cough/sneeze counts between volunteers with medical masks and cotton masks in a bedroom or a car. We concluded that the cotton mask could be a potential substitute for medical mask for respiratory infection person in microenvironment with air conditioning. Healthy people may daily use cotton mask in the community since cotton mask is washable and reusable.", "qid": 18, "docid": "91zxeqwy", "rank": 94, "score": 7.1381988525390625}, {"content": "Title: Nasopharyngeal wash in preventing and treating upper respiratory tract infections: Could it prevent COVID-19? Content: Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has led to the novel coronavirus disease 2019 (COVID-19) pandemic. The current emphasis is on preventive strategies such as social distancing, face mask, and hand washing. The technique of nasopharyngeal wash to prevent the virus from inhabiting and replicating in the nasal and pharyngeal mucosa has been suggested to be useful in reducing symptoms, transmission, and viral shedding in cases of viral acute respiratory tract infections. In rapid systematic review, we found studies showing some improvement in prevention and treatment of upper respiratory tract infections. We postulate that hypertonic saline gargles and nasal wash may be useful in prevention and for care of patients with COVID-19. The present evidence emphasizes the need of randomized controlled trials to evaluate the role and mechanism of nasopharyngeal wash in COVID-19.", "qid": 18, "docid": "c2nkp1gq", "rank": 95, "score": 7.1269001960754395}, {"content": "Title: The Relationship Between COVID-19 Infection and Risk Perception, Knowledge, Attitude As Well As Four Non-pharmaceutical Interventions (NPIs) During the Late Period Of The COVID-19 Epidemic In China An Online Cross-sectional Survey of 8158 Adults Content: Background: So far, there has been no published population study on the relationship between COVID19 infection and public risk perception, information source, knowledge, attitude and four nonpharmaceutical interventions(NPI: hand washing, proper coughing habits, social distancing and mask wearing) during the COVID-19 outbreak in China. Methods: An online survey of 8158 Chinese adults between 22 February to 5 March 2020 was conducted. Bivariate associations between categorical variables were examined using Fisher exact test. We also explored the determinants of four NPIs as well as their association with COVID19 infection using logistic regression. Results: Of 8158 adults included, 57 (0.73%) were infected with COVID19. The overwhelming majority of respondents showed a positive attitude (99.2%), positive risk perception (99.9%) and high knowledge levels that were among the strongest predictors of four highly adopted NPIs (hand washing:96.8%; proper coughing: 93.1%; social distancing:87.1%; mask wearing:97.9%). There was an increased risk of COVID19 infection for those who not washing hands (2.28% vs 0.65%; RR=3.53: 95%CI: 1.538.15; P<0.009); not practicing proper coughing (1.79% vs 0.73%; RR=2.44: 95%CI: 1.15-5.15;P=0.026); not practicing social distancing (1.52% vs 0.58%; RR=2.63:95%CI:1.48 4.67; P=0.002); and not wearing a mask (7.41% vs 0.6%; RR=12.38:95%CI:5.81-26.36; P<0.001). For those who did practice all other three NPIs, wearing mask was associated with significantly reduced risk of infection compared to those who did not wear a mask (0.6% vs 16.7%; p=0.035). Similarly, for those who did not practice all or part of the other three NPIs, wearing mask was also associated with significantly reduced risk of infection. In a penalised logistic regression model including all four NPIs, wearing a mask was the only significant predictor of COVID19 infection among four NPIs (OR=7.20; 95%CI:2.2423.11; p<0.001). Conclusions: We found high levels of risk perception, positive attitude, desirable knowledge as well as a high level of adopting four NPIs. The relevant knowledge, risk perception and attitude were strong predictors of adapting the four NPIs. Mask wearing, among four personal NPIs, is the most effective protective measure against COVID19 infection with added preventive effect among those who practised all or part of the other three NPIs.", "qid": 18, "docid": "xj7xxxpd", "rank": 96, "score": 7.1230998039245605}, {"content": "Title: Barriers and facilitators to healthcare workers' adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis Content: BACKGROUND: This review is one of a series of rapid reviews that Cochrane contributors have prepared to inform the 2020 COVID-19 pandemic. When new respiratory infectious diseases become widespread, such as during the COVID-19 pandemic, healthcare workers' adherence to infection prevention and control (IPC) guidelines becomes even more important. Strategies in these guidelines include the use of personal protective equipment (PPE) such as masks, face shields, gloves and gowns; the separation of patients with respiratory infections from others; and stricter cleaning routines. These strategies can be difficult and time-consuming to adhere to in practice. Authorities and healthcare facilities therefore need to consider how best to support healthcare workers to implement them. OBJECTIVES: To identify barriers and facilitators to healthcare workers' adherence to IPC guidelines for respiratory infectious diseases. SEARCH METHODS: We searched OVID MEDLINE on 26 March 2020. As we searched only one database due to time constraints, we also undertook a rigorous and comprehensive scoping exercise and search of the reference lists of key papers. We did not apply any date limit or language limits. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with a distinct qualitative component) that focused on the experiences and perceptions of healthcare workers towards factors that impact on their ability to adhere to IPC guidelines for respiratory infectious diseases. We included studies of any type of healthcare worker with responsibility for patient care. We included studies that focused on IPC guidelines (local, national or international) for respiratory infectious diseases in any healthcare setting. These selection criteria were framed by an understanding of the needs of health workers during the COVID-19 pandemic. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed the titles, abstracts and full texts identified by our search. We used a prespecified sampling frame to sample from the eligible studies, aiming to capture a range of respiratory infectious disease types, geographical spread and data-rich studies. We extracted data using a data extraction form designed for this synthesis. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool. We used a 'best fit framework approach' to analyse and synthesise the evidence. This provided upfront analytical categories, with scope for further thematic analysis. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and developed implications for practice. MAIN RESULTS: We found 36 relevant studies and sampled 20 of these studies for our analysis. Ten of these studies were from Asia, four from Africa, four from Central and North America and two from Australia. The studies explored the views and experiences of nurses, doctors and other healthcare workers when dealing with severe acute respiratory syndrome (SARS), H1N1, MERS (Middle East respiratory syndrome), tuberculosis (TB), or seasonal influenza. Most of these healthcare workers worked in hospitals; others worked in primary and community care settings. Our review points to several barriers and facilitators that influenced healthcare workers' ability to adhere to IPC guidelines. The following factors are based on findings assessed as of moderate to high confidence. Healthcare workers felt unsure as to how to adhere to local guidelines when they were long and ambiguous or did not reflect national or international guidelines. They could feel overwhelmed because local guidelines were constantly changing. They also described how IPC strategies led to increased workloads and fatigue, for instance because they had to use PPE and take on additional cleaning. Healthcare workers described how their responses to IPC guidelines were influenced by the level of support they felt that they received from their management team. Clear communication about IPC guidelines was seen as vital. But healthcare workers pointed to a lack of training about the infection itself and about how to use PPE. They also thought it was a problem when training was not mandatory. Sufficient space to isolate patients was also seen as vital. A lack of isolation rooms, anterooms and shower facilities was a problem. Other important practical measures described by healthcare workers included minimising overcrowding, fast-tracking infected patients, restricting visitors, and providing easy access to handwashing facilities. A lack of PPE, and equipment that was of poor quality, was a serious concern for healthcare workers and managers. They also pointed to the need to adjust the volume of supplies as infection outbreaks continued. Healthcare workers believed that they followed IPC guidance more closely when they saw the value of it. Some healthcare workers felt motivated to follow the guidance because of fear of infecting themselves or their families, or because they felt responsible for their patients. Some healthcare workers found it difficult to use masks and other equipment when it made patients feel isolated, frightened or stigmatised. Healthcare workers also found masks and other equipment uncomfortable to use. The workplace culture could also influence whether healthcare workers followed IPC guidelines or not. Across many of the findings, healthcare workers pointed to the importance of including all staff, including cleaning staff, porters, kitchen staff and other support staff when implementing IPC guidelines. AUTHORS' CONCLUSIONS: Healthcare workers point to several factors that influence their ability and willingness to follow IPC guidelines when managing respiratory infectious diseases. These include factors tied to the guideline itself and how it is communicated, support from managers, workplace culture, training, physical space, access to and trust in personal protective equipment, and a desire to deliver good patient care. The review also highlights the importance of including all facility staff, including support staff, when implementing IPC guidelines.", "qid": 18, "docid": "5fcvpvgf", "rank": 97, "score": 7.117199897766113}, {"content": "Title: Barriers and facilitators to healthcare workers' adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis. Content: BACKGROUND This review is one of a series of rapid reviews that Cochrane contributors have prepared to inform the 2020 COVID-19 pandemic. When new respiratory infectious diseases become widespread, such as during the COVID-19 pandemic, healthcare workers' adherence to infection prevention and control (IPC) guidelines becomes even more important. Strategies in these guidelines include the use of personal protective equipment (PPE) such as masks, face shields, gloves and gowns; the separation of patients with respiratory infections from others; and stricter cleaning routines. These strategies can be difficult and time-consuming to adhere to in practice. Authorities and healthcare facilities therefore need to consider how best to support healthcare workers to implement them. OBJECTIVES To identify barriers and facilitators to healthcare workers' adherence to IPC guidelines for respiratory infectious diseases. SEARCH METHODS We searched OVID MEDLINE on 26 March 2020. As we searched only one database due to time constraints, we also undertook a rigorous and comprehensive scoping exercise and search of the reference lists of key papers. We did not apply any date limit or language limits. SELECTION CRITERIA We included qualitative and mixed-methods studies (with a distinct qualitative component) that focused on the experiences and perceptions of healthcare workers towards factors that impact on their ability to adhere to IPC guidelines for respiratory infectious diseases. We included studies of any type of healthcare worker with responsibility for patient care. We included studies that focused on IPC guidelines (local, national or international) for respiratory infectious diseases in any healthcare setting. These selection criteria were framed by an understanding of the needs of health workers during the COVID-19 pandemic. DATA COLLECTION AND ANALYSIS Four review authors independently assessed the titles, abstracts and full texts identified by our search. We used a prespecified sampling frame to sample from the eligible studies, aiming to capture a range of respiratory infectious disease types, geographical spread and data-rich studies. We extracted data using a data extraction form designed for this synthesis. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool. We used a 'best fit framework approach' to analyse and synthesise the evidence. This provided upfront analytical categories, with scope for further thematic analysis. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and developed implications for practice. MAIN RESULTS We found 36 relevant studies and sampled 20 of these studies for our analysis. Ten of these studies were from Asia, four from Africa, four from Central and North America and two from Australia. The studies explored the views and experiences of nurses, doctors and other healthcare workers when dealing with severe acute respiratory syndrome (SARS), H1N1, MERS (Middle East respiratory syndrome), tuberculosis (TB), or seasonal influenza. Most of these healthcare workers worked in hospitals; others worked in primary and community care settings. Our review points to several barriers and facilitators that influenced healthcare workers' ability to adhere to IPC guidelines. The following factors are based on findings assessed as of moderate to high confidence. Healthcare workers felt unsure as to how to adhere to local guidelines when they were long and ambiguous or did not reflect national or international guidelines. They could feel overwhelmed because local guidelines were constantly changing. They also described how IPC strategies led to increased workloads and fatigue, for instance because they had to use PPE and take on additional cleaning. Healthcare workers described how their responses to IPC guidelines were influenced by the level of support they felt that they received from their management team. Clear communication about IPC guidelines was seen as vital. But healthcare workers pointed to a lack of training about the infection itself and about how to use PPE. They also thought it was a problem when training was not mandatory. Sufficient space to isolate patients was also seen as vital. A lack of isolation rooms, anterooms and shower facilities was a problem. Other important practical measures described by healthcare workers included minimising overcrowding, fast-tracking infected patients, restricting visitors, and providing easy access to handwashing facilities. A lack of PPE, and equipment that was of poor quality, was a serious concern for healthcare workers and managers. They also pointed to the need to adjust the volume of supplies as infection outbreaks continued. Healthcare workers believed that they followed IPC guidance more closely when they saw the value of it. Some healthcare workers felt motivated to follow the guidance because of fear of infecting themselves or their families, or because they felt responsible for their patients. Some healthcare workers found it difficult to use masks and other equipment when it made patients feel isolated, frightened or stigmatised. Healthcare workers also found masks and other equipment uncomfortable to use. The workplace culture could also influence whether healthcare workers followed IPC guidelines or not. Across many of the findings, healthcare workers pointed to the importance of including all staff, including cleaning staff, porters, kitchen staff and other support staff when implementing IPC guidelines. AUTHORS' CONCLUSIONS Healthcare workers point to several factors that influence their ability and willingness to follow IPC guidelines when managing respiratory infectious diseases. These include factors tied to the guideline itself and how it is communicated, support from managers, workplace culture, training, physical space, access to and trust in personal protective equipment, and a desire to deliver good patient care. The review also highlights the importance of including all facility staff, including support staff, when implementing IPC guidelines.", "qid": 18, "docid": "yxtyufhi", "rank": 98, "score": 7.117198944091797}, {"content": "Title: Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma Content: Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are \"low cost\" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.", "qid": 18, "docid": "1c3fpazy", "rank": 99, "score": 7.117000102996826}, {"content": "Title: Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. Content: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.", "qid": 18, "docid": "5hei9fac", "rank": 100, "score": 7.1132001876831055}]}
{"query": "what type of hand sanitizer is needed to destroy Covid-19?", "hits": [{"content": "Title: Hand Sanitizers: A Review of Ingredients, Mechanisms of Action, Modes of Delivery, and Efficacy Against Coronaviruses Content: BACKGROUND: The emergence of the novel virus, SARS-CoV-2, has posed unprecedented challenges to public health around the world. Currently, strategies to deal with COVID-19 are purely supportive and preventative, aimed at reducing transmission. An effective and simple method for reducing transmission of infections in the public or healthcare settings is hand hygiene. Unfortunately, little is known regarding the efficacy of hand sanitizers against SARS-CoV-2. METHODS: In this review, an extensive literature search was performed to succinctly summarize the primary active ingredients and mechanisms of action of hand sanitizers, compare the effectiveness and compliance of gel and foam sanitizers, and predict whether alcohol and non-alcohol hand sanitizers would be effective against SARS-CoV-2. RESULTS: Most alcohol based hand sanitizers are effective at inactivating enveloped viruses, including coronaviruses. With what is currently known in the literature, one may not confidently suggest one mode of hand sanitizing delivery over the other. When hand washing with soap and water is unavailable, a sufficient volume of sanitizer is necessary to ensure complete hand coverage, and compliance is critical for appropriate hand hygiene. CONCLUSIONS: By extrapolating effectiveness of hand sanitizers on viruses of similar structure to SARS-CoV-2, this virus should be effectively inactivated with current hand hygiene products, though future research should attempt to determine this directly.", "qid": 19, "docid": "y777xosr", "rank": 1, "score": 12.068400382995605}, {"content": "Title: Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 10. Alcohol-based antiseptics for hand disinfection and a comparison of their effectiveness with soaps. Content: Alcohol compounds are increasingly used as a substitute for hand washing in health care environments and some public places because these compounds are easy to use and do not require water or hand drying materials. However, the effectiveness of these compounds depends on how much soil (bioburden) is present on the hands. Workers in health care environments and other public places must wash their hands before using antiseptics and/or wearing gloves. However, alcohol-based antiseptics, also called rubs and sanitizers, can be very effective for rapidly destroying some pathogens by the action of the aqueous alcohol solution without the need for water or drying with towels. Alcohol-based compounds seem to be the most effective treatment against gram-negative bacteria on lightly soiled hands, but antimicrobial soaps are as good or better when hands are more heavily contaminated. Instant sanitizers have no residual effect, unlike some antimicrobial soaps that retain antimicrobial activity after the hygienic action has been completed, e.g., after hand washing. Many alcohol-based hand rubs have antimicrobial agents added to them, but each formulation must be evaluated against the target pathogens in the environment of concern before being considered for use. Wipes also are widely used for quick cleanups of hands, other body parts, and surfaces. These wipes often contain alcohol and/or antimicrobial compounds and are used for personal hygiene where water is limited. However, antiseptics and wipes are not panaceas for every situation and are less effective in the presence of more than a light soil load and against most enteric viruses.", "qid": 19, "docid": "1lx84td6", "rank": 2, "score": 11.550100326538086}, {"content": "Title: European Task Force on Contact Dermatitis statement on coronavirus 19 disease (COVID-19) outbreak and the risk of adverse cutaneous reactions. Content: Among the basic protective measures against COVID-19, the need to wash hands frequently and in a prolonged way using soap, and to regularly use alcohol-based hand sanitizers is well established for the whole population. Healthcare workers in general, and particularly those involved in the direct care of COVID-19 patients, have to wear personal protective equipment (PPE) daily for many hours and also accomplish general preventive measurements outside their work. Cutaneous adverse reactions can develop that need to be prevented, identified and therapeutically managed. According to the data reported by Lin et al 1 , based in the experience from healthcare workers in Wuhan, adverse skin reactions were reported in 74% of responders (n=376) to a general survey. The most commonly reported types of eruptions were skin dryness or desquamation (68.6%), papules or erythema (60.4%) and maceration (52,9%).", "qid": 19, "docid": "gfyup5aj", "rank": 3, "score": 10.55720043182373}, {"content": "Title: The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies Content: Abstract With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products\u2019 lifecycle, including distribution, manufacture and import.", "qid": 19, "docid": "20ipkh78", "rank": 4, "score": 10.516300201416016}, {"content": "Title: The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies Content: With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products' lifecycle, including distribution, manufacture and import.", "qid": 19, "docid": "uhhk4t7f", "rank": 5, "score": 10.5162992477417}, {"content": "Title: Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations Content: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%\u201395% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "qid": 19, "docid": "d26y5291", "rank": 6, "score": 10.340999603271484}, {"content": "Title: Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations Content: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%-95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "qid": 19, "docid": "i0ll585x", "rank": 7, "score": 10.340998649597168}, {"content": "Title: Hidden threat lurking behind the alcohol sanitizers in COVID\u201019 outbreak Content: The ongoing COVID\u201019 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "qid": 19, "docid": "hx8c0mxj", "rank": 8, "score": 10.292200088500977}, {"content": "Title: Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak Content: The ongoing COVID-19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "qid": 19, "docid": "z6cda4o2", "rank": 9, "score": 10.29219913482666}, {"content": "Title: Dry Taps? A Synthesis of Alternative \u201cWash\u201d Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings Content: Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "qid": 19, "docid": "nl55rm8o", "rank": 10, "score": 9.941200256347656}, {"content": "Title: Dry Taps? A Synthesis of Alternative \"Wash\" Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings Content: Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "qid": 19, "docid": "ojh3vgrb", "rank": 11, "score": 9.94119930267334}, {"content": "Title: COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways Content: Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "qid": 19, "docid": "eevs62xf", "rank": 12, "score": 9.915900230407715}, {"content": "Title: COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways Content: Abstract Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "qid": 19, "docid": "hma2kvn2", "rank": 13, "score": 9.915899276733398}, {"content": "Title: Sanitizer aerosol-driven ocular surface disease (SADOSD)-A COVID-19 repercussion? Content: Since the onset of the COVID-19 pandemic, there has been an advisory for regular and thorough cleaning of hands besides other measures such as social distancing and self-isolation. The rationale for the same is to prevent the transfer of the virus from hands that have come in contact with fomites. While both alcohol-based hand rubs (ABHR) or washing with soap and water are claimed to have been effective, hand sanitizers have gained more popularity due to the ease of use. The increased frequency of ABHR use and the aerosols generated pose a potential threat to the skin and exposed mucosal surfaces, especially that of the eye due to the proximity of use. The adverse effects of alcohol in these sanitizers can be manifold. An allergic or inflammatory response can occur depending on the predisposing or preexisting conditions. This article describes the risks, underlying mechanisms, and preventive measures for sanitizer aerosol-driven ocular surface disease.", "qid": 19, "docid": "yjg54yyk", "rank": 14, "score": 9.821599960327148}, {"content": "Title: Redesigning a large school-based clinical trial in response to changes in community practice Content: Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer\u2019s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.", "qid": 19, "docid": "1zzyfmkb", "rank": 15, "score": 9.783499717712402}, {"content": "Title: Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment Content: AIM: In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD: Simple experiments to assess the levels of absorption by each route separately. RESULTS: Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION: Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.", "qid": 19, "docid": "adnd1odw", "rank": 16, "score": 9.682299613952637}, {"content": "Title: Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment. Content: AIM In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD Simple experiments to assess the levels of absorption by each route separately. RESULTS Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.", "qid": 19, "docid": "ld141phd", "rank": 17, "score": 9.68229866027832}, {"content": "Title: Onset of occupational hand eczema among healthcare workers during the SARS-CoV-2 pandemic: Comparing a single surgical site with a COVID-19 intensive care unit Content: BACKGROUND: As a result of the COVID-19 outbreak, hygiene regulations have been revised and hand sanitation has been intensified. OBJECTIVE: To investigate the onset of hand eczema during the COVID-19 pandemic in healthcare workers (HCWs) directly involved in intensive care of COVID-19 patients and HCWs without direct contact with COVID-19 patients. Hereby, we aim at increasing awareness about occupational hand eczema and preventive measures that can be adopted. METHOD: A survey was distributed amongst 114 HCWs at a single surgical centre and at a COVID-19 intensive care unit of the university hospital Ludwig Maximilian University Munich, Germany. Participants were questioned about the daily frequency of hand hygiene prior to and during the pandemic. Participants self-reported the onset of hand eczema and associated symptoms. RESULTS: Our study revealed a significant increase in hand washing, disinfection, and use of hand cream across all participants (P-value <.001), regardless of having direct contact with COVID-19 patients. A high prevalence of symptoms associated with acute hand dermatitis of 90.4% was found across all HCWs, whereas hand eczema itself was underreported (14.9%). CONCLUSION: The increase in hand sanitation during the COVID-19 pandemic impairs the skin of the hands across all HCWs, independent of direct intensive care of affected patients.", "qid": 19, "docid": "0k4k95q7", "rank": 18, "score": 9.571700096130371}, {"content": "Title: Onset of occupational hand eczema among healthcare workers during the SARS\u2010CoV\u20102 pandemic \u2013 comparing a single surgical site with a COVID\u201019 intensive care unit Content: BACKGROUND: Due to the COVID\u201019 outbreak, hygiene regulations have been intensified and hand sanitation has gained special attention. OBJECTIVE: To investigate the onset of hand eczema during the COVID\u201019 pandemic in health care workers (HCWs) directly involved in intensive care of COVID\u201019 patients and HCWs without direct contact. Hereby, we aim at increasing awareness with regard to occupational hand eczema and preventive measures that can be undertaken. METHODS: A survey was distributed amongst 114 HCWs at a single surgical site and at a COVID\u201019 intensive care unit of the university hospital LMU Munich, Germany. Participants were questioned with regard to the daily frequency of hand hygiene prior to and during the pandemic. Participants self\u2010reported onset of hand eczema and associated symptoms. RESULTS: Our study revealed a significant increase of hand washing, disinfection and use of hand cream across all participants (P\u2010value<.001), regardless of having direct contact with COVID\u201019 patients. A high prevalence of symptoms associated with acute hand dermatitis was found in 90.4% across all HCWs, whereas hand eczema itself was underreported (14.9%). CONCLUSION: The increase of hand sanitation during the COVID\u201019 pandemic impairs the skin of the hands across all HCWs, independent of direct intensive care of affected patients. This article is protected by copyright. All rights reserved.", "qid": 19, "docid": "hr5su8z3", "rank": 19, "score": 9.541299819946289}, {"content": "Title: Thoughts on What Chemists Can Contribute to Fighting SARS\u2010CoV\u20102 \u2013 A Short Note on Hand Sanitizers, Drug Candidates and Outreach Content: The SARS\u2010CoV\u20102 outbreak causing the respiratory disease COVID\u201019 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three\u2010pronged approach is proposed.", "qid": 19, "docid": "kuwargnp", "rank": 20, "score": 9.413399696350098}, {"content": "Title: Thoughts on What Chemists Can Contribute to Fighting SARS-CoV-2 - A Short Note on Hand Sanitizers, Drug Candidates and Outreach Content: The SARS-CoV-2 outbreak causing the respiratory disease COVID-19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three-pronged approach is proposed.", "qid": 19, "docid": "uqxl4xux", "rank": 21, "score": 9.413398742675781}, {"content": "Title: A systematic review of the effectiveness of antimicrobial rinse-free hand sanitizers for prevention of illness-related absenteeism in elementary school children Content: BACKGROUND: Absenteeism due to communicable illness is a major problem encountered by North American elementary school children. Although handwashing is a proven infection control measure, barriers exist in the school environment, which hinder compliance to this routine. Currently, alternative hand hygiene techniques are being considered, and one such technique is the use of antimicrobial rinse-free hand sanitizers. METHODS: A systematic review was conducted to examine the effectiveness of antimicrobial rinse-free hand sanitizer interventions in the elementary school setting. MEDLINE, EMBASE, Biological Abstract, CINAHL, HealthSTAR and Cochrane Controlled Trials Register were searched for both randomized and non-randomized controlled trials. Absenteeism due to communicable illness was the primary outcome variable. RESULTS: Six eligible studies, two of which were randomized, were identified (5 published studies, 1 published abstract). The quality of reporting was low. Due to a large amount of heterogeneity and low quality of reporting, no pooled estimates were calculated. There was a significant difference reported in favor of the intervention in all 5 published studies. CONCLUSIONS: The available evidence for the effectiveness of antimicrobial rinse-free hand sanitizer in the school environment is of low quality. The results suggest that the strength of the benefit should be interpreted with caution. Given the potential to reduce student absenteeism, teacher absenteeism, school operating costs, healthcare costs and parental absenteeism, a well-designed and analyzed trial is needed to optimize this hand hygiene technique.", "qid": 19, "docid": "47ema2dq", "rank": 22, "score": 9.300800323486328}, {"content": "Title: Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis Content: Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host\u2013apoptosis\u2013virus triangle.", "qid": 19, "docid": "3hxau5vt", "rank": 23, "score": 9.292900085449219}, {"content": "Title: Frequent Hand Washing for COVID-19 Prevention Can Cause Hand Dermatitis: Management Tips Content: Coronavirus disease 2019 (COVID-19) continues to spread globally, outpacing the capacity and resources of health systems worldwide. A therapeutic vaccine is not yet on the rise, and preventive measures are the current approach to restraint the transmission of cases. As the virus is highly contagious via respiratory route (droplets from infected persons, widely spread by coughing or sneezing) and via contact with contaminated surfaces, community transmission and spread can be decreased through the practice of regular and diligent hand hygiene. Frequent hand washing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. These skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. In the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules.", "qid": 19, "docid": "irmwqjfh", "rank": 24, "score": 9.283300399780273}, {"content": "Title: Limiting Spread of COVID-19 in Ghana: Compliance audit of selected transportation stations in the Greater Accra region of Ghana Content: Globally, little evidence exists on transmission patterns of COVID-19. Recommendations to prevent infection include appropriate and frequent handwashing plus physical and social distancing. We conducted an exploratory observational study to assess compliance with these recommendations in selected transportation stations in Ghana. A one-hour audit of 45 public transport stations in the Greater Accra region was carried out between 27th and 29th March 2020. Using an adapted World Health Organization (WHO) hand hygiene assessment scale, the availability and use of handwashing facilities, social distancing, and ongoing public education on COVID-19 prevention measures were assessed, weighted and scored to determine the level of compliance of stations. Compliance with recommendations was categorized as 'inadequate', 'basic', 'intermediate' and 'advanced', based on the overall score. Majority (80%) of stations in Accra have at least one Veronica Bucket with flowing water and soap, but the number of washing places at each station is not adequate. Only a small minority (18%) of stations were communicating the need to wash hands frequently and appropriately, and to practice social/physical distancing while at the station. In most stations (95%), hand washing practice was either not observed, or only infrequently. Almost all stations (93%) did not have alcohol-based hand sanitizers available for public use, while social distancing was rarely practiced (only 2%). In over 90% of the stations, face masks were either not worn or only worn by a few passengers. Compliance with COVID-19 prevention measures was inadequate in 13 stations, basic in 16 stations, intermediate in 7 stations, and advanced in 9 stations. Compliance with COVID-19 prevention measures in public transportation stations in the Greater Accra region remains a challenge. Awareness creation should aim to elevate COVID-19 risk perception of transportation operators and clients. Transport operators and stations need support and guidance to enforce hand washing and social distancing.", "qid": 19, "docid": "dyfvsxnz", "rank": 25, "score": 9.03849983215332}, {"content": "Title: Compounds Derived from Epigallocatechin-3-Gallate (EGCG) as a Novel Approach to the Prevention of Viral Infections. Content: Pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. These lead to large number of illnesses and deaths worldwide each year. Outbreaks of emerging lethal viruses, such as Ebola virus, severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus, could lead to epidemics or even pandemics if they are not effectively controlled. Current strategies to prevent viral entry into the human body are focused on cleansing the surface of the skin that covers hands and fingers. Surface protection and disinfection against microorganisms, including viruses, is performed by sanitization of the skin surface through hand washing with soap and water, surface disinfectants, and hand sanitizers, particularly alcohol-based hand sanitizers. However, concerns about the overall ineffectiveness, toxicity of certain ingredients of disinfectants, pollution of the environment, and the short duration of antimicrobial activity of alcohol have not been addressed, and the epidemiology of certain major viral infections are not correlated inversely with the current measures of viral prevention. In addition to a short duration on the skin surface, alcohol is ineffective against certain viruses such as norovirus, rabies virus, and polio virus. There is a need for a novel approach to protect humans and livestock from infections of pathogenic viruses that is broadly effective, long-lasting (persistent), non-toxic, and environment-friendly. A strong candidate is a group of unique compounds found in Camellia sinensis (tea plant): the green tea polyphenols, in particular epigallocatechin-3-gallate (EGCG) and its lipophilic derivatives. This review discussed the weaknesses of current hand sanitizers, gathered published results from many studies on the antiviral activities of EGCG and its lipophilic derivatives, and the potential use of these compounds as a novel strategy for disease prevention, especially against pathogenic viruses.", "qid": 19, "docid": "xa95ubvs", "rank": 26, "score": 8.925800323486328}, {"content": "Title: Impact of non-pharmaceutical interventions on URIs and influenza in crowded, urban households. Content: OBJECTIVES We compared the impact of three household interventions-education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks-on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates. METHODS A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months. RESULTS We recorded 5034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p < 0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p < 0.0001). The proportion of households that reported > or = 50% of members receiving influenza vaccine increased during the study (p < 0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0-5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p < 0.02). CONCLUSIONS In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact.", "qid": 19, "docid": "7agyp81c", "rank": 27, "score": 8.913900375366211}, {"content": "Title: Formulation and efficacy evaluation of the safe and efficient moisturizing snow mushroom hand sanitizer Content: OBJECTIVES: Snow fungus or snow mushroom or white jelly mushroom (Tremella fuciformis), the edible mushroom, was formulated into hand sanitizer in form of moisturizing alcohol\u2010based hand rubs (ABHR) gel. METHODS: The stable base ABHRs were developed. The preferred bases were incorporated with various concentrations of snow mushroom extract. The stable and preferred snow mushroom ABHR was moisturizing and sanitizing efficacies evaluated in 20 human volunteers in a comparison with its placebo. RESULTS: The stable hand sanitizer gel bases containing 66.5% of ethanol and 0.3% triclosan were developed and incorporated with the extract of snow mushroom polysaccharide. Of which, the preparations containing 10% of snow mushroom and 0.3% of gelling agent gained the highest preferences as assessed in 20 Thai volunteers. The snow mushroom hand sanitizer was proved to be none irritated in the same group of the volunteers as was the placebo. The snow mushroom gel significantly (P < 0.05) moist the skin better than the placebo at all time of the interval assessment until the end of the study at 180 min. The hand sanitizers were confirmed on their anti\u2010septic, at which the efficacies of the active and placebo ABHR were comparable (P = 0.90). CONCLUSIONS: Snow mushroom ABHR gel with its confirmed moisturizing and sanitizing efficacies is presented. It is meetings with the recommendation on hand hygienic improvement to combat the infections of diseases spreading. The preparation can be frequency applied with its proved skin hydrating efficacy co\u2010contributes in a good condition of hand hygiene.", "qid": 19, "docid": "3tlpyw4s", "rank": 28, "score": 8.846199989318848}, {"content": "Title: Formulation and efficacy evaluation of the safe and efficient moisturizing snow mushroom hand sanitizer Content: OBJECTIVES: Snow fungus or snow mushroom or white jelly mushroom (Tremella fuciformis), the edible mushroom, was formulated into hand sanitizer in form of moisturizing alcohol-based hand rub (ABHR) gel. METHODS: The stable base ABHRs were developed. The preferred bases were incorporated with various concentrations of snow mushroom extract. The stable and preferred snow mushroom ABHR was moisturizing and sanitizing efficacies evaluated in 20 human volunteers in comparison with its placebo. RESULTS: The stable hand sanitizer gel bases containing 66.5% of ethanol and 0.3% of triclosan were developed and incorporated with the extract of snow mushroom polysaccharide. Of which, the preparations containing 10% of snow mushroom and 0.3% of gelling agent gained the highest preferences as assessed in 20 Thai volunteers. The snow mushroom hand sanitizer was proved to be none irritated in the same group of the volunteers as was the placebo. The snow mushroom gel significantly (P < .05) moist the skin better than the placebo at all time of the interval assessment until the end of the study at 180 minutes. The hand sanitizers were confirmed on their anti-septic, at which the efficacies of the active and placebo ABHR were comparable (P = .90). CONCLUSIONS: Snow mushroom ABHR gel with its confirmed moisturizing and sanitizing efficacies is presented. It is meetings with the recommendation on hand hygienic improvement to combat the infections of diseases spreading. The preparation can be frequency applied with its proved skin hydrating efficacy co-contributes in a good condition of hand hygiene.", "qid": 19, "docid": "u7pflnxk", "rank": 29, "score": 8.846199035644531}, {"content": "Title: Efficacy of Instant Hand Sanitizers against Foodborne Pathogens Compared with Hand Washing with Soap and Water in Food Preparation Settings: A Systematic Review. Content: Hands can be a vector for transmitting pathogenic microorganisms to foodstuffs and drinks, and to the mouths of susceptible hosts. Hand washing is the primary barrier to prevent transmission of enteric pathogens via cross-contamination from infected persons. Conventional hand washing involves the use of water, soap, and friction to remove dirt and microorganisms. The availability of hand sanitizing products for use when water and soap are unavailable has increased in recent years. The aim of this systematic review was to collate scientific information on the efficacy of hand sanitizers compared with washing hands with soap and water for the removal of foodborne pathogens from the hands of food handlers. An extensive literature search was carried out using three electronic databases: Web of Science, Scopus, and PubMed. Twenty-eight scientific publications were ultimately included in the review. Analysis of this literature revealed various limitations in the scientific information owing to the absence of a standardized protocol for evaluating the efficacy of hand products and variation in experimental conditions. However, despite conflicting results, scientific evidence seems to support the historical skepticism about the use of waterless hand sanitizers in food preparation settings. Water and soap appear to be more effective than waterless products for removal of soil and microorganisms from hands. Alcohol-based products achieve rapid and effective inactivation of various bacteria, but their efficacy is generally lower against nonenveloped viruses. The presence of food debris significantly affects the microbial inactivation rate of hand sanitizers.", "qid": 19, "docid": "zyw3bpbr", "rank": 30, "score": 8.7475004196167}, {"content": "Title: Effects of Response Cost and Socially-Assisted Interventions on Hand-Hygiene Behavior of University Students Content: A field study was conducted to examine the effect of interventions to increase hand-hygiene behavior of university students. Student patrons of a university cafeteria were observed during lunch. Across several phases, researchers observed and recorded the number of students (a) entering the restroom to wash hands and (b) using a hand-sanitizer gel. Interventions included an informational poster, hand-sanitizer dispenser, and change agent to increase hand-hygiene behavior. Results showed that the presence of a strategically placed hand-sanitizer dispenser was effective in increasing hand-hygiene behavior from 1.52% to over 60% (average n = 208 students per day). Participants were particularly responsive to the hand-sanitizer dispenser when combined with a change agent. Meanwhile, the tested interventions were ineffective in increasing the number of students entering a restroom to hand wash. The results are discussed regarding response cost and socially-mediated consequences of change agents.", "qid": 19, "docid": "gjy7ydqu", "rank": 31, "score": 8.679300308227539}, {"content": "Title: Pharmacies on the Frontline: Responding to the COVID-19 Pandemic Content: The year 2020 will infamously be known for the COVID-19 pandemic It certainly caught most of the population completely off-guard and forever changed their lives Unfortunately, this pandemic is expected to make a resurgence in the fall, but hopefully more will be known about SARS-CoV-2, better treatment protocols will be established, and, possibly, a safe and effective vaccine will be developed and available soon There are numerous drug shortages due to the COVID-19 pandemic Some products are not commercially available in certain dosage forms needed by patients Pharmacies (retail, independents, health systems) all over the U S are being asked to compound items such as hand sanitizers, saccharin solutions for FIT testing of N95 masks, and hydroxychloroquine suspension The commercial lopinavir/ritonavir oral liquid is in short supply and may need to be compounded soon We are all in this one together, from the essential workers to the children, and pharmacists are emerging as one of the first-line responders", "qid": 19, "docid": "4qzunyly", "rank": 32, "score": 8.629199981689453}, {"content": "Title: Pharmacies on the Frontline: Responding to the COVID-19 Pandemic. Content: The year 2020 will infamously be known for the COVID-19 pandemic. It certainly caught most of the population completely off-guard and forever changed their lives. Unfortunately, this pandemic is expected to make a resurgence in the fall, but hopefully more will be known about SARS-CoV-2, better treatment protocols will be established, and, possibly, a safe and effective vaccine will be developed and available soon. There are numerous drug shortages due to the COVID-19 pandemic. Some products are not commercially available in certain dosage forms needed by patients. Pharmacies (retail, independents, health systems) all over the U.S. are being asked to compound items such as hand sanitizers, saccharin solutions for FIT testing of N95 masks, and hydroxychloroquine suspension. The commercial lopinavir/ritonavir oral liquid is in short supply and may need to be compounded soon. We are all in this one together, from the essential workers to the children, and pharmacists are emerging as one of the first-line responders.", "qid": 19, "docid": "w5ii5rq7", "rank": 33, "score": 8.629199028015137}, {"content": "Title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 Content: Our surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers.", "qid": 19, "docid": "0qfoc553", "rank": 34, "score": 8.612199783325195}, {"content": "Title: Determinants of safety-focused product purchasing in the United States at the beginning of the global COVID-19 pandemic Content: Public preparation for the COVID-19 pandemic was widely covered in the media due to its intensity and fast-pace. While some individuals prepared with personal safety supplies such as soap and hand sanitizer, many others did not purchase such preparatory products. There are many health and safety benefits to quick engagement and emergency preparedness in a pandemic, and it is important to identify those who conduct these behaviors. The present study examined who engaged in preparatory purchasing of safety and health care products during the early stages of the spread of COVID-19 and what stimulated this action. Results of a cross-sectional study (N = 344) indicates that possessing, or uncertainty about possessing a COVID-19 risk factor (but not differences in age, gender, race, or income), increased purchasing of preparatory health and safety products. Also, in line with past research on risk, affect, and behavior, worry mediated this relationship. Further, gender moderated the relationship between worry and purchasing, such that worry increased product purchasing for men, who were initially low in worry, but not for women. This study lends additional support to worry as a mediator between risk and safety-related behavior and has implications for understanding factors related to preparatory purchasing of health care products during pandemics.", "qid": 19, "docid": "h1x55p2v", "rank": 35, "score": 8.593000411987305}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: Abstract The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 19, "docid": "qud4bj12", "rank": 36, "score": 8.526800155639648}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 19, "docid": "xfwseuxu", "rank": 37, "score": 8.526799201965332}, {"content": "Title: Associations Between Hand Hygiene Education and Self-Reported Hand-Washing Behaviors Among Korean Adults During MERS-CoV Outbreak Content: Background. Hand washing is an effective way to prevent transmission of infectious diseases. Education and promotional materials about hand washing may change individuals\u2019 awareness toward hand washing. Infectious disease outbreak may also affect individuals\u2019 awareness. Aims. Our study aimed to examine associations between hand-washing education and self-reported hand-washing behaviors among Korean adults during the year of the Middle East respiratory syndrome (MERS) outbreak. Methods. Data from the 2015 Community Health Survey were used for this study. The total study population comprised 222,599 individuals who were older than 20 years of age. A multiple linear regression model was used to investigate associations between hand hygiene education and self-reported hand-washing behaviors. Subgroup analyses stratified by age, sex, income, and MERS outbreak regions were also performed. Results. Individuals who received hand-washing education or saw promotional materials related to hand washing had significantly higher scores for self-reported use of soap or sanitizer (\u03b2 = 0.177, P < .0001) and self-reported frequency of hand washing (\u03b2 = 0.481, P < .0001) than those who did not have such experiences. The effect of hand-washing education on self-reported behavior change was greater among older adults, women, and lower income earners. The effect of hand hygiene education on self-reported use of soap or sanitizer was similar regardless of whether the participants lived in MERS regions. Conclusion. Our findings emphasize the importance of education or promotions encouraging hand washing, especially for older adults, women, and lower income earners. In addition, MERS outbreak itself affected individuals\u2019 awareness of hand-washing behaviors. Well-organized campaigns that consider these factors are needed to prevent infectious diseases.", "qid": 19, "docid": "xsfolppr", "rank": 38, "score": 8.44890022277832}, {"content": "Title: Food Safety and COVID-19: Precautionary Measures to Limit the Spread of Coronavirus at Food Service and Retail Sector Content: Coronavirus pandemic has drastically upended the daily life routines of human beings and has wide wide-ranging effects on entire sectors of society The food sector is also susceptible and substantially harmed by the influence of intensive effects of coronavirus To ensure food safety and limit the spread of coronavirus at food services and retail sector has become a challenge where delicate and fresh food items are served and delivered to the customers, which have passed through a series of operational steps from order taking, food receiving, preparation of food, packing, delivery to customers At each step, there is a possibility of food handlers to touch the food surface or food directly and if food handler is not following appropriate precautionary measures e g hand hygiene, sanitization and disinfection, social distances, and is touching, then it can be a possible source of coronavirus spread Since there is no evidence that food is a coronavirus transmission route but during the food operations, improper sanitization and disinfection of key touchpoints, food contact, nonfood contact, equipment and cleaning tools surfaces and close contact of food handlers with staff and customers not only can put themselves on risk but can also be a risk for customers Food services and the retail sector should make sure proper hand hygiene, approved sanitizers and disinfectants in use, follow social distances at workstations and while interacting with the customers Finally, the business should be vigilant to monitor the temperature of staff and incoming guests to identify if there may any sick person to avoid from further spread of coronavirus and shall report to concerned health authorities if anyone symptoms matching with COVID-19", "qid": 19, "docid": "j7jy3va4", "rank": 39, "score": 8.448899269104004}, {"content": "Title: Local response in health emergencies: key considerations for addressing the COVID-19 pandemic in informal urban settlements Content: This paper highlights the major challenges and considerations for addressing COVID-19 in informal settlements. It discusses what is known about vulnerabilities and how to support local protective action. There is heightened concern about informal urban settlements because of the combination of population density and inadequate access to water and sanitation, which makes standard advice about social distancing and washing hands implausible. There are further challenges to do with the lack of reliable data and the social, political and economic contexts in each setting that will influence vulnerability and possibilities for action. The potential health impacts of COVID-19 are immense in informal settlements, but if control measures are poorly executed these could also have severe negative impacts. Public health interventions must be balanced with social and economic interventions, especially in relation to the informal economy upon which many poor urban residents depend. Local residents, leaders and community-based groups must be engaged and resourced to develop locally appropriate control strategies, in partnership with local governments and authorities. Historically, informal settlements and their residents have been stigmatized, blamed, and subjected to rules and regulations that are unaffordable or unfeasible to adhere to. Responses to COVID-19 should not repeat these mistakes. Priorities for enabling effective control measures include: collaborating with local residents who have unsurpassed knowledge of relevant spatial and social infrastructures, strengthening coordination with local governments, and investing in improved data for monitoring the response in informal settlements.", "qid": 19, "docid": "znlnqs2k", "rank": 40, "score": 8.416799545288086}, {"content": "Title: Tailoring of the ongoing water, sanitation and hygiene interventions for prevention and control of COVID-19 Content: Water, sanitation, and hygiene (WASH) interventions remain to be important in the prevention of further spread of coronavirus disease-2019 (COVID-19). Basic hygiene interventions such as handwashing with water and soap (HWWS) when applied consistently will deactivate and remove the virus particles from the hands. Realizing the efforts that have been made by countries world over in controlling the COVID-19, this letter seeks to discuss how the available WASH services can be used in the fight against further spread of COVID-19. The letter highlights the challenges being faced by the current WASH services in middle- and low-income countries and suggests measures that can be employed to strengthen the WASH services in this period of the COVID-19 pandemic.", "qid": 19, "docid": "5uc76djv", "rank": 41, "score": 8.40999984741211}, {"content": "Title: Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe Acute Respiratory Syndrome-Coronavirus-2? Content: A novel virus named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China in late 2019. Since then, the virus has quickly spread worldwide, leading the World Health Organization to declare it as a pandemic; by the end of April 2020, the number of cases exceeded 3 million. Due to the high infectivity rate, SARS-CoV-2 is difficult to contain, making disinfectant protocols vital, especially for essential, highly trafficked areas such as hospitals, grocery stores, and delivery centers. According to the Centers for Disease Control and Prevention, best practices to slow the spread rely on good hand hygiene, including proper handwashing practices as well as the use of alcohol-based hand sanitizers. However, they provide warning against sanitizing products containing benzalkonium chloride (BAC), which has sparked concern in both the scientific community as well as the general public as BAC, a common quaternary ammonium compound (QAC), is ubiquitous in soaps and cleaning wipes as well as hospital sanitation kits. This viewpoint aims to highlight the outdated and incongruous data in the evaluation of BAC against the family of known coronaviruses and points to the need for further evaluation of the efficacy of QACs against coronaviruses.", "qid": 19, "docid": "9ksiyyqe", "rank": 42, "score": 8.398599624633789}, {"content": "Title: Exploring the correlation between COVID-19 fatalities and poor WASH (Water, Sanitation and Hygiene) services Content: Access to safe Water, Sanitation and Hygiene (WASH) services have been recognized as a highly precautionary measure essential to protecting human health during this COVID-19 outbreak. However, it is currently unknown whether poor or non- availability of these services are also closely related to COVID-19 fatalities. We analysed the latest data on COVID-19 fatality rates in Sub Saharan Africa with indicators of safe water and sanitation governance to test this hypothesis. We found a strong correlation between a higher case fatality rate and poorer access to safe drinking water as well as safe sanitation. The Pearson correlation is stronger for access to safe sanitation ( -0.30) compared to access to safe drinking water (-0.20). The Chad, Niger and Sierra Leone were amongst the countries with the highest fatality rates (>6.0) and also had particularly poor access to safe drinking water (<34%) and safe sanitation (<22%). The hypothesis of an association between COVID-19 fatalities and poor access to water and sanitation was confirmed by this study. However, our analysis does not establish causality. Given the increase spread of COVID-19 and related deaths, this analysis serves as an important reminder that safe water and sanitation services are key for public health interventions and highlights the need to prioritise this sector in all economies.", "qid": 19, "docid": "cdbiphrr", "rank": 43, "score": 8.345800399780273}, {"content": "Title: SARS-CoV-2 RNA detection in the air and on surfaces in the COVID-19 ward of a hospital in Milan, Italy Content: The COVID-19 outbreak has rapidly progressed worldwide finding the health system, scientists and society unprepared to face a little-known, fast spreading, and extremely deadly virus. Italy is one of the countries hardest hit by the pandemic, resulting in healthcare facilities bearing heavy burdens and severe restrictive measures. Despite efforts to clarify the virus transmission, especially in indoor scenarios, several aspects of SARS-CoV-2 spread are still rudimentary. This study evaluated the contamination of the air and surfaces by SARS-CoV-2 RNA in the COVID-19 isolation ward of a hospital in Milan, Italy. A total of 42 air and surface samples were collected inside five different zones of the ward including contaminated (COVID-19 patients' area), semi-contaminated (undressing room), and clean areas. SARS-CoV-2 RNA detection was performed using real time reverse transcription polymerase chain reaction. Overall, 24.3% of swab samples were positive, but none of these were collected in the clean area. Thus, the positivity rate was higher in contaminated (35.0%) and semi-contaminated (50.0%) areas than in clean areas (0.0%; P<0.05). The most contaminated surfaces were hand sanitizer dispensers (100.0%), medical equipment (50.0%), medical equipment touch screens (50.0%), shelves for medical equipment (40.0%), bedrails (33.3%), and door handles (25.0%). All the air samples collected from the contaminated area, namely the intensive care unit and corridor, were positive while viral RNA was not detected in either semi-contaminated or clean areas. These results showed that environmental contamination did not involve clean areas, but the results also support the need for strict disinfection, hand hygiene and protective measures for healthcare workers as well as the need for airborne isolation precautions.", "qid": 19, "docid": "xu46bduc", "rank": 44, "score": 8.302300453186035}, {"content": "Title: Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand. Content: The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "qid": 19, "docid": "d6v5mkj7", "rank": 45, "score": 8.161199569702148}, {"content": "Title: Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand Content: The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "qid": 19, "docid": "rv2akbj8", "rank": 46, "score": 8.161198616027832}, {"content": "Title: Walkthrough Sanitization Gates for COVID-19: A Preventive Measure or Public Health Concern? Content: As the COVID-19 pandemic continues to gain momentum around the world, several measures are being put in place to control its spread. One such effort includes the installation walkthrough sanitization gates to disinfect passersby and prevent cross infection. However, there is lack of clinical evidence on the effectiveness of these walkthrough gates to contain COVID-19. Moreover, there are potential public health concerns associated with these walkthrough gates. Spraying individuals with disinfectant chemicals is strongly discouraged by various health authorities around the globe because of their propensity for eye and skin irritation, bronchospasm following inhalation, and gastrointestinal effects such as nausea and vomiting. This article underscores that the risks associated with the use of these walkthrough gates overweigh any potential benefits. Health authorities must discourage their use and should focus efforts on other preventive measures such as social distancing, wearing masks, and hand hygiene to prevent the spread of COVID-19 among the general public.", "qid": 19, "docid": "b5xae518", "rank": 47, "score": 8.130900382995605}, {"content": "Title: Efficacy of disinfectants and hand sanitizers against avian respiratory viruses. Content: Disinfectants play a major role in the control of animal diseases by decontaminating the farm environment. We evaluated the virucidal efficacy of nine commonly used disinfectants on a nonporous surface contaminated experimentally with avian metapneumovirus (aMPV), avian influenza virus, or Newcastle disease virus (NDV). Phenolic compounds and glutaraldehyde were found to be the most effective against all three viruses. Quaternary ammonium compounds were effective against aMPV but not against the other two viruses. In addition, efficacy of commercially available hand sanitizers was evaluated on human fingers contaminated with aMPV and NDV. All three hand sanitizers tested were found to be effective against both viruses within 1 min of application on fingers.", "qid": 19, "docid": "lbu2xbqh", "rank": 48, "score": 7.966100215911865}, {"content": "Title: Preparation of alcohol-based handrub in COVID-19 Alsatian cluster Content: Alsace, in particular Haut-Rhin, is one of the main clusters of COVID-19 in France There has been a shortage of essential supplies in the area, especially alcohol-based hand sanitizer In this context, and in accordance with the decree dated March 6, 2020, our hospital management team asked us to start local production of alcohol-based handrub This was a real challenge: In one week, we had to implement the production of handrub to meet the needs of a 1,400-bed hospital The production had to comply with the French preparation guidelines and take place on specific premises, with qualified and calibrated equipment, by qualified staff, under the supervision of a pharmacist The other big challenge we faced was the supply of pharmaceutical raw and packaging materials During this particular critical period, all suppliers were out of stock Here, we describe the organizational set-up and the decisions made, e g , to use technical-grade ethanol before the publication of the decrees dated March 13 and March 23, 2020", "qid": 19, "docid": "p5hvf569", "rank": 49, "score": 7.928199768066406}, {"content": "Title: Mobile Virology Research and Diagnostic Laboratory (MVRDL: BSL-3) for COVID-19 Screening, Virus Culturing and Vaccine Development Content: In order to prevent spread of COVID-19, World Health Organization (WHO) has specified that measures such as cleaning hands regularly with alcohol-based hand sanitizer or washing with soap and water, avoiding touching nose, eyes, mouth and social distancing should be followed by people. Another important measure for containing spread is by Testing\u2013Testing and Testing. To conduct real-time reverse transcription polymerase chain reaction (rRT-PCR) test for diagnosing COVID-19. Possibility to test up to 2000 samples per day. For virus culturing for drug screening, convalescent plasma-derived therapy. To aid in the development of vaccine and development of diagnostic kits.", "qid": 19, "docid": "fjiffj86", "rank": 50, "score": 7.9166998863220215}, {"content": "Title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. Content: BACKGROUND In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants) coveralls were more difficult to doff than isolation gowns (very low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). According to three studies that tested more recently introduced full-body PPE ensembles, there may be no difference in contamination. Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.", "qid": 19, "docid": "e9kroam2", "rank": 51, "score": 7.897799968719482}, {"content": "Title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. Content: BACKGROUND In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.", "qid": 19, "docid": "how1mfvf", "rank": 52, "score": 7.897799015045166}, {"content": "Title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff Content: BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.", "qid": 19, "docid": "kmb6128p", "rank": 53, "score": 7.89779806137085}, {"content": "Title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff Content: BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants) coveralls were more difficult to doff than isolation gowns (very low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). According to three studies that tested more recently introduced full-body PPE ensembles, there may be no difference in contamination. Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.", "qid": 19, "docid": "qkntdq8q", "rank": 54, "score": 7.897797107696533}, {"content": "Title: Hand hygiene in high-complexity sectors as an integrating element in the combat of Sars-CoV-2 Content: OBJECTIVE: to perform a situational diagnosis of the behavior of health professionals concerning hand hygiene practices in highly-complex sectors. METHODS: this quantitative and retrospective study was based on reports (2016 and 2017) of Adult and Pediatric ICUs of a Federal hospital in Rio de Janeiro. RESULTS: one thousand two hundred fifty-eight opportunities for hand hygiene were analysed. The chance of professionals sanitizing hands in Pediatric ICUs is 41.61% higher than in Adult ICUs. Concerning proper hand hygiene, the medical team had a 39.44% lower chance than the nursing team. Others had a 30.62% lower chance when compared to the nursing team. The moment \"after contact with the patient\" presented 4.5275 times the chance in relation \"before contact with the patient\". CONCLUSION: in front of hand hygiene recommendations to control COVID-19, diagnostic assessment and previous analysis of the behavior of professionals proved to be positive.", "qid": 19, "docid": "56ibvpfy", "rank": 55, "score": 7.877699851989746}, {"content": "Title: Hand hygiene in high-complexity sectors as an integrating element in the combat of Sars-CoV-2. Content: OBJECTIVE to perform a situational diagnosis of the behavior of health professionals concerning hand hygiene practices in highly-complex sectors. METHODS this quantitative and retrospective study was based on reports (2016 and 2017) of Adult and Pediatric ICUs of a Federal hospital in Rio de Janeiro. RESULTS one thousand two hundred fifty-eight opportunities for hand hygiene were analysed. The chance of professionals sanitizing hands in Pediatric ICUs is 41.61% higher than in Adult ICUs. Concerning proper hand hygiene, the medical team had a 39.44% lower chance than the nursing team. Others had a 30.62% lower chance when compared to the nursing team. The moment \"after contact with the patient\" presented 4.5275 times the chance in relation \"before contact with the patient\". CONCLUSION in front of hand hygiene recommendations to control COVID-19, diagnostic assessment and previous analysis of the behavior of professionals proved to be positive.", "qid": 19, "docid": "xga0lncp", "rank": 56, "score": 7.87769889831543}, {"content": "Title: Bovine coronavirus hemagglutinin protein Content: Abstract Treatment of purified bovine coronavirus (Mebus strain) with pronase destroyed the integrity of virion surface glycoproteins gp140, gp120, gp100, reduced the amount of gp26 and destroyed the hemagglutinating activity of the virus. Bromelain, on the other hand, destroyed the integrity of gp120, gp100 and gp26 but failed to remove gp140 and failed to destroy viral hemagglutinating activity. These experiments suggest that gp140 is the virion hemagglutinin. Immunoblotting studies using monospecific antiserum demonstrate that gp140 is a disulfide-linked dimeric structure reducible to monomers of 65 kDa.", "qid": 19, "docid": "h6vwbldi", "rank": 57, "score": 7.858399868011475}, {"content": "Title: Infection control influence of Middle East respiratory syndrome coronavirus: A hospital-based analysis Content: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) caused multiple outbreaks. Such outbreaks increase economic and infection control burdens. We studied the infection control influence of MERS-CoV using a hospital-based analysis. METHODS: Our hospital had 17 positive and 82 negative cases of MERS-CoV between April 1, 2013, and June 3, 2013. The study evaluated the impact of these cases on the use of gloves, surgical masks, N95 respirators, alcohol-based hand sanitizer, and soap, as well as hand hygiene compliance rates. RESULTS: During the study, the use of personal protective equipment during MERS-CoV compared with theperiod before MERS-CoV increased dramatically from 2,947.4 to 10,283.9 per 1,000 patient-days (P<.0000001) for surgical masks and from 22 to 232 per 1,000 patient-days (P <.0000001) for N95 masks. The use of alcohol-based hand sanitizer and soap showed a significant increase in utilized amount (P<.0000001). Hand hygiene compliance rates increased from 73% just before the occurrence of the first MERS case to 88% during MERS cases (P = .0001). The monthly added cost was $16,400 for included infection control items. CONCLUSIONS: There was a significant increase in the utilization of surgical masks, respirators, soap and alcohol-based hand sanitizers. Such an increase is a challenge and adds cost to the healthcare system.", "qid": 19, "docid": "mcmazu1v", "rank": 58, "score": 7.837399959564209}, {"content": "Title: 4.06 Safe Sanitation in Low Economic Development Areas Content: This chapter presents the advances in sanitation for developing countries as well as the needs in terms of goals, standards, technology, and policy. To understand why a special chapter for low-income areas is needed, it describes the main types of pollutants, their origins, and treatment options. As part of the text and to face the requirements for poor rural and urban areas and water-scarce regions, basic sanitation, wastewater treatment, and water reuse alternatives are described with emphasis on their constraints and limitations for developing countries. Some aspects concerning the development of policies, costs, and funding to fulfill the Millennium Development Goals are also included. The importance of developing innovative solutions that can be sustainable, affordable, and progressively implemented is discussed.", "qid": 19, "docid": "xxov2x33", "rank": 59, "score": 7.799200057983398}, {"content": "Title: Hand Hygiene and Tuberculosis Risk in Korea: An Ecological Association. Content: Hand hygiene is a basic but effective strategy against infectious disease. This study investigated an ecological association between hand hygiene and tuberculosis (TB) risk in Korea. Hand hygiene data were obtained from the 2015 Community Health Survey. Information on TB incidence and mortality in 2015 were obtained from the National Infectious Diseases Surveillance System and death monitoring database, respectively. In multiple linear regression analysis, frequent hand washing rates after using the restroom (B = -0.78, P = .037), after returning from the outdoors (B = -0.28, P = .049), and with soap or hand sanitizer (B = -0.54, P = .018) were negatively associated with TB incidence. TB mortality were associated with frequent hand washing rates after returning from the outdoors (B = -0.05, P = .035), and with soap or hand sanitizer (B = -0.10, P = .010), respectively. Hand washing was associated with lower TB incidence and mortality at the community level. These results could contribute to develop community-based health promotion strategies.", "qid": 19, "docid": "wva4rc56", "rank": 60, "score": 7.798799991607666}, {"content": "Title: SARS-CoV-2 infection among returnees on charter flights to Japan from Hubei, China: a report from National Center for Global Health and Medicine Content: Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province Japanese citizens lost a means of transportation to return back to Japan The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences A total of five charter flights were dispatched, and the majority of returnees (793/829 [95 7%]) were handled at NCGM A large number of personnel from various departments participated in this operation;107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total Several medical translators were also involved In this operation, we conducted airborne precautions in addition to contact precautions Eye shields were also used The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets Enhanced hand hygiene using alcohol hand sanitizer was performed Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34) Of those hospitalized after NCGM triage, 8 3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8 3%] vs 9/745 [1 2%]: p = 0 0057) NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area We were able to establish a scheme through this experience that can be used in the future", "qid": 19, "docid": "8jn7ph8g", "rank": 61, "score": 7.7846999168396}, {"content": "Title: The Flow Physics of COVID-19 Content: Flow physics plays a key role in nearly every facet of the COVID-19 pandemic. This includes the generation and aerosolization of virus-laden respiratory droplets from a host, its airborne dispersion and deposition on surfaces, as well as the subsequent inhalation of these bioaerosols by unsuspecting recipients. Fluid dynamics is also key to preventative measures such as the use of face masks, hand-washing, ventilation of indoor environments, and even social distancing. This article summarizes what we know, and more importantly, what we need to learn about the science underlying these issues so that we are better prepared to tackle the next outbreak of COVID-19 or a similar disease.", "qid": 19, "docid": "7is71518", "rank": 62, "score": 7.7820000648498535}, {"content": "Title: Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? Content: SARS-CoV-2, the etiologic agent of COVID-19, is shed in stool. SARS coronaviruses have been detected in wastewater during outbreaks in China, Europe, and the United States. In this perspective, we outline the risk fecal shedding poses at locations without safely managed sanitation, as in most of Nigeria where we work. We believe that feco-oral transmission could occur if community transmission becomes high and sustained in densely populated cities without proper sanitation in Nigeria and many other African and Asian settings. In the absence of basic sanitation, or where existing sanitation is not safely managed, groundwater, which is often drawn up from wells and boreholes for drinking and household use, can become contaminated with enteric bacteria and viruses from fecal matter. Endemic and epidemic transmission of multiple feco-oral pathogens via this route continues to be documented in areas without safely managed sanitation, and, therefore, the risk of SARS-CoV-2 transmission needs to be evaluated, tracked, and forestalled in such settings. We suggest that fecal matter from treatment facilities and recovered patients should be carefully and properly disposed. Furthermore, environmental surveillance of SARS-CoV-2 in wastewater and accumulated human waste, as well as efforts to mitigate the virus' entry into unprotected household water sources, should be a priority part of the COVID-19 response in settings without safely managed sanitation for the duration of the pandemic.", "qid": 19, "docid": "ibohbjfb", "rank": 63, "score": 7.779300212860107}, {"content": "Title: Environmental contamination of SARS-CoV-2 in healthcare premises Content: OBJECTIVES: A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. METHODS: We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. RESULTS: The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. CONCLUSION: Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.", "qid": 19, "docid": "swspqrrk", "rank": 64, "score": 7.588900089263916}, {"content": "Title: Environmental Contamination of SARS-CoV-2 in Healthcare Premises Content: Abstract Objectives A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Methods We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. Conclusion Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.", "qid": 19, "docid": "txtrbqxj", "rank": 65, "score": 7.5888991355896}, {"content": "Title: The Covid-19 pandemic's effects on poor rural dwellers in sub-Saharan Africa: A case study of access to basic clean water, sanitary systems and hand-washing facilities Content: The fear of the invisible but prevalent Coronavirus (COVID-19), disease cannot be overemphasized since there is the potential possibility of it wiping out the entire world population within a few months if adequate and quick steps are not taken to curb this menace, and the sub-Saharan African (SSAn) region is no exception. It is evident that water, as an essential daily commodity, has long been in a state of emergency in SSAn nations, which is largely attributed to decades of neglect by the successive governments, because it has not been possible to separate the existing bond between water, health, livelihood and the economy. The laudable Millennium Development Goals (MDGs) proposed by the United Nations had yet to achieve the stated objective of improving the standards of living and health conditions of the rural communities in the SSAn region before the COVID-19 pandemic outbreak. This failure has been masked by a sort of delusion in which the people of this region are subjected to the hardship of searching for clean and healthy water in their own ponds, rivers, streams and shallow hand-dug local wells on a continuous basis. Less than 17% of the rural population in all the SSAn communities can access basic hand-washing facilities and sanitation systems. The total water productivity, as measured by the Gross Domestic Product (GDP) per cubic meter of total freshwater withdrawn, for the people was less than 5 GDP.", "qid": 19, "docid": "jdkikd29", "rank": 66, "score": 7.538300037384033}, {"content": "Title: Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey Content: BACKGROUND: The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area. METHODS: We conducted an online, cross-sectional social media survey from March 14 \u2013 April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S. RESULTS: The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement. CONCLUSION: These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed.", "qid": 19, "docid": "24xxj8q8", "rank": 67, "score": 7.530900001525879}, {"content": "Title: Information Seeking Responses to News of Local COVID-19 Cases: Evidence from Internet Search Data Content: The novel coronavirus (COVID-19) outbreak is a global pandemic with community circulation in many countries, including the U.S. where every state is reporting confirmed cases. The course of this pandemic will be largely shaped by how governments enact timely policies, disseminate the information, and most importantly, how the public reacts to them. Here, we examine informationseeking responses to the first COVID-19 case public announcement in a state. By using an eventstudy framework, we show that such news increases collective attention to the crisis right away, but the elevated level of attention is short-lived, even though the initial announcements were followed by increasingly strong measures. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms and hand sanitizer. On the other hand, searches for information regarding community level policies (e.g., quarantine, school closures, testing), or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are encouraging given our study period is relatively early in the epidemic and more elaborate policy responses were not yet part of the public discourse. Further analysis will track evolving patterns of responses to subsequent flows of public information.", "qid": 19, "docid": "gtmpd7t0", "rank": 68, "score": 7.509799957275391}, {"content": "Title: Effectiveness of hand hygiene and provision of information in preventing influenza cases requiring hospitalization Content: Abstract Background The objective of the study was to investigate the effectiveness of non-pharmacological interventions in preventing cases of influenza requiring hospitalization. Methods We performed a multicenter case-control study in 36 hospitals, in 2010 in Spain. Hospitalized influenza cases confirmed by reverse-transcription polymerase chain reaction and three matched controls (two hospital and one community control) per case were selected. The use of non-pharmacological measures seven days before the onset of symptoms (frequency of hand washing, use of alcohol-based hand sanitizers and handwashing after touching contaminated surfaces) was collected. Results We studied 813 cases hospitalized for influenza and 2274 controls. The frequency of hand washing 5-10 times (adjusted odds ratio [aOR]=0.65) and >10 times (aOR=0.59) and handwashing after contact with contaminated surfaces (aOR=0.65) were protective factors and were dose-responsive (p<0.001). Alcohol-based hand sanitizers were associated with marginal benefits (aOR=0.82). Conclusions Frequent handwashing should be recommended to prevent influenza cases requiring hospitalization.", "qid": 19, "docid": "706bf8qr", "rank": 69, "score": 7.502399921417236}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Since the emergence of the COVID-19 pandemic in December 2019 in Wuhan, China, there have been nearly 6,663,304 confirmed cases of COVID-19, including 392,802 deaths, worldwide as of 10:00 CEST 06 June 2020. In Africa, 152,442 COVID-19 cases and 4334 deaths have been reported as of 02 June 2020. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, and the rest of world, has had to swiftly undertake the necessary measures to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting systems, and insufficient numbers of medical staff. The COVID-19 pandemic poses a great threat to most African countries, from cities to rural areas, and has created a strong demand on already scarce resources. Intense mobilization of additional resources is required to implement established emergency contingency measures. Measures to prevent the spread of COVID-19 include closure of borders and restricting movement of people within a country; this has resulted in the tourism sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 19, "docid": "h3czhqtt", "rank": 70, "score": 7.495800018310547}, {"content": "Title: The effectiveness of hand hygiene procedures in reducing the risks of infections in home and community settings including handwashing and alcohol-based hand sanitizers Content: Infectious diseases (ID) circulating in the home and community remain a significant concern. Several demographic, environmental, and health care trends, as reviewed in this report, are combining to make it likely that the threat of ID will increase in coming years. Two factors are largely responsible for this trend: first, the constantly changing nature and range of pathogens to which we are exposed and, secondly, the demographic changes occurring in the community, which affect our resistance to infection. This report reviews the evidence base related to the impact of hand hygiene in reducing transmission of ID in the home and community. The report focuses on developed countries, most particularly North America and Europe. It also evaluates the use of alcohol-based hygiene procedures as an alternative to, or in conjunction with, handwashing. The report compiles data from intervention studies and considers it alongside risk modeling approaches (both qualitative and quantitative) based on microbiologic data. The main conclusions are as follows: (1) Hand hygiene is a key component of good hygiene practice in the home and community and can produce significant benefits in terms of reducing the incidence of infection, most particularly gastrointestinal infections but also respiratory tract and skin infections. (2) Decontamination of hands can be carried out either by handwashing with soap or by use of waterless hand sanitizers, which reduce contamination on hands by removal or by killing the organisms in situ. The health impact of hand hygiene within a given community can be increased by using products and procedures, either alone or in sequence, that maximize the log reduction of both bacteria and viruses on hands. (3) The impact of hand hygiene in reducing ID risks could be increased by convincing people to apply hand hygiene procedures correctly (eg, wash their hands correctly) and at the correct time. (4) To optimize health benefits, promotion of hand hygiene should be accompanied by hygiene education and should also involve promotion of other aspects of hygiene.", "qid": 19, "docid": "lyewg2c9", "rank": 71, "score": 7.493100166320801}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Abstract Since the emergence of the pandemic in December 2019 in Wuhan, China, as of 10:00 CEST, June 6, 2020, there have been nearly 6,663,304 confirmed cases of COVID-19 including 392,802 deaths worldwide. In Africa, as of June 2, 2020, a total of 152,442 COVID-19 cases and 4334 deaths have been reported. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, together with the rest of world have had to swiftly undertake measures necessary to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting system and insufficient number of medical staff. The COVID-19 pandemic poses a great threat to most African countries from cities to rural areas and has created a strong demand on already scarce resources and requires an intense mobilization of additional resources to implement established emergency contingency measures. Closure of borders and movements of people restrictions within the country as measures to prevent the spread of COVID-19; this has resulted in the sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 19, "docid": "juvmabdq", "rank": 72, "score": 7.471399784088135}, {"content": "Title: Comparison of hemagglutinating, receptor-destroying, and acetylesterase activities of avirulent and virulent bovine coronavirus strains Content: Hemagglutinating and acetylesterase functions as well as the 124 kDa glycoprotein were present in the highly cell-culture adapted, avirulent bovine coronavirus strain BCV-L9, in the Norden vaccine strain derived from it, and in 5 wild-type, virulent strains that multiplied in HRT-18 cells but were restricted in several types of cultured bovine cells. The BCV-L9 and the wild-type strain BCV-LY-138 agglutinated chicken and mouse erythrocytes. The acetylesterase facilitated break-down of the BCV-erythrocyte complex with chicken but only to a minimal extent with mouse erythrocytes in the receptor-destroying enzyme test. Purified preparations of the vaccine and the wild-type strains agglutinated chicken erythrocytes at low titers and mouse erythrocytes at 128 to 256 times higher titers whereas receptor destroying enzyme activity was detectable only with chicken erythrocytes. When wild-type strains were propagated in HRT cells at low passage levels, they produced 5\u00d710(5) to 4.5\u00d710(6) plaque forming units per 50 \u00b5l which agglutinated erythrocytes from mice but not from chickens. Diisopropylfluoro-phosphate moderately increased the hemagglutination titers, but completely inhibited the receptor destroying enzyme of purified virus of all strains. It had virtually no influence on the plaque-forming infectivity of the different BCV strains. The acetylesterase of strain BCV-L9 reacting in the receptor-destroying enzyme test was stable for 3h at 37 and 42\u00b0C. It was inactivated within 30 min at 56\u00b0C while the hemagglutinin function of this strain was stable for 3 h at 37, 42, and 56\u00b0C, but it was inactivated at 65\u00b0C within 1 h.", "qid": 19, "docid": "tycuoslv", "rank": 73, "score": 7.409900188446045}, {"content": "Title: What can a Pandemic Teach Us about Competency Based Medical Education? Content: Medical education is moving towards competency-based medical education (CBME) where learning and assessment are focused on predefined abilities and outcomes. While medical student and residency training have defined competencies and objectives that trainees need to achieve, training remains time -based. Students and residents graduate based on a preset length of training. The COVID -19 pandemic is disrupting educational and clinical environments and in some regions the workforce may not be adequate to respond to the needs of the community. This, therefore, presents an opportunity for the medical education community to reconsider time-based training and embrace a competency-based progression to accelerate entry into the workforce. This commentary discusses undergraduate and graduate medical education response to workforce pressures of COVID-19. On one hand, some medical schools are moving towards competency-based (early) graduation from medical school. On the other hand, residency programs have generally held to time -based completion of training. In the context of this clinical and educational disruption, there are two challenges to CBME progression of trainees. The first challenge is whether there is trust in competency-based assessment to permit time independent progression. The second involves a number of logistical issues to competency-based progression.", "qid": 19, "docid": "ovef7ff1", "rank": 74, "score": 7.404399871826172}, {"content": "Title: Cold Plasma: Clean Technology to Destroy Pathogenic Micro-organisms Content: Atmospheric pressure cold plasma is a promising technology in fighting pathogenic micro-organisms. In times of Covid-19 pandemic, it was decided to modify two types of cold plasma devices to study their effectiveness in the killing of pathogenic micro-organisms. These studies have shown that both the devices are efficient in this purpose. While pencil like microwave based device can destroy Aeromonas bacteria and its bacteriophage from 6 cm distance in 2 min, the larger (~ 40 cm(2)) RF plasma based device could do the similar killing ability for the larger possible area in 4 min. Optical Emission Spectroscopy (OES) studies revealed that both these devices produce OH radicals which helped in the destruction of both bacteria and its bacteriophage. With suitable modifications, these devices, especially the larger area device may even be implemented for the elimination of Covid-19 affected wards of hospital without using any sensitive chemical process.", "qid": 19, "docid": "6e8lti9a", "rank": 75, "score": 7.360300064086914}, {"content": "Title: COViD-19: Face Mask Effectiveness, Hand Sanitizer Shortages, and Rapid Medication Therapy Trials Content: The COVID-19 pandemic is a rapidly evolving phenomenon that presents serious practical challenges and complex clinical considerations for health care workers, health care administrators, and policy formulators. The Senior Care Pharmacist carries periodic updates addressing matters relevant to pharmacotherapeutics and pharmacy practice as these relate to the care of older people in the time of the pandemic. The brief news items that are provided here are not intended to be substitutes for a careful and comprehensive consideration of the issues involved, but rather, they serve to provide initial awareness of concepts and to stimulate more complete situational analysis.", "qid": 19, "docid": "uhip2tim", "rank": 76, "score": 7.3024001121521}, {"content": "Title: COViD-19: Face Mask Effectiveness, Hand Sanitizer Shortages, and Rapid Medication Therapy Trials. Content: The COVID-19 pandemic is a rapidly evolving phenomenon that presents serious practical challenges and complex clinical considerations for health care workers, health care administrators, and policy formulators. The Senior Care Pharmacist carries periodic updates addressing matters relevant to pharmacotherapeutics and pharmacy practice as these relate to the care of older people in the time of the pandemic. The brief news items that are provided here are not intended to be substitutes for a careful and comprehensive consideration of the issues involved, but rather, they serve to provide initial awareness of concepts and to stimulate more complete situational analysis.", "qid": 19, "docid": "zx5e92ur", "rank": 77, "score": 7.302399158477783}, {"content": "Title: Evidence from internet search data shows information-seeking responses to news of local COVID-19 cases Content: The COVID-19 outbreak is a global pandemic with community circulation in many countries, including the United States, with confirmed cases in all states. The course of this pandemic will be shaped by how governments enact timely policies and disseminate information and by how the public reacts to policies and information. Here, we examine information-seeking responses to the first COVID-19 case public announcement in a state. Using an event study framework for all US states, we show that such news increases collective attention to the crisis right away. However, the elevated level of attention is short-lived, even though the initial announcements are followed by increasingly strong policy measures. Specifically, searches for \u201ccoronavirus\u201d increased by about 36% (95% CI: 27 to 44%) on the day immediately after the first case announcement but decreased back to the baseline level in less than a week or two. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms, and hand sanitizer. On the other hand, searches for information regarding community-level policies (e.g., quarantine, school closures, testing) or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are representative of the study period being relatively early in the epidemic, and more-elaborate policy responses were not yet part of the public discourse. Further analysis should track evolving patterns of responses to subsequent flows of public information.", "qid": 19, "docid": "0m4nkufg", "rank": 78, "score": 7.260700225830078}, {"content": "Title: Evidence from internet search data shows information-seeking responses to news of local COVID-19 cases Content: The COVID-19 outbreak is a global pandemic with community circulation in many countries, including the United States, with confirmed cases in all states. The course of this pandemic will be shaped by how governments enact timely policies and disseminate information and by how the public reacts to policies and information. Here, we examine information-seeking responses to the first COVID-19 case public announcement in a state. Using an event study framework for all US states, we show that such news increases collective attention to the crisis right away. However, the elevated level of attention is short-lived, even though the initial announcements are followed by increasingly strong policy measures. Specifically, searches for \"coronavirus\" increased by about 36% (95% CI: 27 to 44%) on the day immediately after the first case announcement but decreased back to the baseline level in less than a week or two. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms, and hand sanitizer. On the other hand, searches for information regarding community-level policies (e.g., quarantine, school closures, testing) or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are representative of the study period being relatively early in the epidemic, and more-elaborate policy responses were not yet part of the public discourse. Further analysis should track evolving patterns of responses to subsequent flows of public information.", "qid": 19, "docid": "3rsbtrzh", "rank": 79, "score": 7.260699272155762}, {"content": "Title: Public Interest in Preventive Measures of Coronavirus Disease 2019 Associated With Timely Issuance of Statewide Stay-at-Home Orders Content: INTRODUCTION: One method of monitoring public preparedness is through measuring public interest in preventive measures. The objective of this study was to analyze public interest in the coronavirus disease 2019 (COVID-19) preventive measures and to identify variables associated with timely stay-at-home (SAH) orders issued by governors. METHODS: State-level search volume was collected from Google Trends. Average preventive measure interest was calculated for the query terms \"hand sanitizer,\" \"hand washing,\" \"social distancing,\" and \"COVID testing.\" We then calculated the delay in statewide SAH orders from March 1, 2020, to the date of issuance and by-state presidential voting percentage. Bivariate correlations were computed to assess the relationship between interest in preventive measures and SAH order delay. RESULTS: The correlation between average preventive measure interest and length of time before the SAH order was placed was -0.47. Average preventive measure interest was also inversely related to voting for a Republican presidential nominee in the 2016 election (R = -0.75), the latter of which was positively associated with longer delays in SAH orders (R = 0.48). CONCLUSIONS: States with greater public interest in COVID-19 preventive measures were inversely related to governor issuance of timely SAH orders. Increasing public interest in preventive measures may slow the spread of the virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by improving preparedness.", "qid": 19, "docid": "3n5ibzri", "rank": 80, "score": 7.256800174713135}, {"content": "Title: Public Interest in Preventive Measures of Coronavirus Disease 2019 Associated With Timely Issuance of Statewide Stay-at-Home Orders Content: INTRODUCTION: One method of monitoring public preparedness is through measuring public interest in preventive measures. The objective of this study was to analyze public interest in the coronavirus disease 2019 (COVID-19) preventive measures and to identify variables associated with timely stay-at-home (SAH) orders issued by governors. METHODS: State-level search volume was collected from Google Trends. Average preventive measure interest was calculated for the query terms \u201chand sanitizer,\u201d \u201chand washing,\u201d \u201csocial distancing,\u201d and \u201cCOVID testing.\u201d We then calculated the delay in statewide SAH orders from March 1, 2020, to the date of issuance and by-state presidential voting percentage. Bivariate correlations were computed to assess the relationship between interest in preventive measures and SAH order delay. RESULTS: The correlation between average preventive measure interest and length of time before the SAH order was placed was \u22120.47. Average preventive measure interest was also inversely related to voting for a Republican presidential nominee in the 2016 election (R = \u22120.75), the latter of which was positively associated with longer delays in SAH orders (R = 0.48). CONCLUSIONS: States with greater public interest in COVID-19 preventive measures were inversely related to governor issuance of timely SAH orders. Increasing public interest in preventive measures may slow the spread of the virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by improving preparedness.", "qid": 19, "docid": "uojx65oh", "rank": 81, "score": 7.256799221038818}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child's will must not be forced.Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation. What is Known: \u00e2\u0080\u00a2 Asymptomatic people can transmit and become important sources of COVID-19. \u00e2\u0080\u00a2 Asymptomatic cases are common also in pediatrics. What is New: \u00e2\u0080\u00a2 Universal use of face masks for success against COVID-19 seems necessary also in pediatric age when people have to go out in their everyday lives. \u00e2\u0080\u00a2 In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons with the main aim to obtain child cooperation.", "qid": 19, "docid": "471z07ac", "rank": 82, "score": 7.201900005340576}, {"content": "Title: What makes non-cirrhotic portal hypertension a common disease in India? Analysis for environmental factors Content: In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.", "qid": 19, "docid": "4c7nal02", "rank": 83, "score": 7.1905999183654785}, {"content": "Title: A web survey to assess the use efficacy of personnel protective materials among allied health care workers during COVID-19 pandemic at North-East India Content: The rising pandemic is resulting in increased usage of personnel protective equipment in the hospital and community. The efficient and effective use of appropriate personal protective equipment will help assure its availability and healthcare provider safety. The purpose of this study was to assess the use efficacy of PPE among health care workers through a web based survey during the pandemic. the response rate of the survey was 66.75%. 35.2% gave a full rating on a point of 5 regarding the control measures taken by the hospital , 39% of respondents did not use the PPE, 90.6% used a surgical mask while 65.9% wore the disposable gloves and only 47.6% wore the goggles/face shield More than half the respondents did not wear the shoe-cover. 97.4% used the hand sanitizer and around 97% maintained hand hygiene practice.", "qid": 19, "docid": "vsrblj3x", "rank": 84, "score": 7.174499988555908}, {"content": "Title: Does communicable diseases (including COVID-19) may increase global poverty risk? A cloud on the horizon Content: Coronavirus epidemic can push millions of people in poverty. The shortage of healthcare resources, lack of sanitation, and population compactness leads to an increase in communicable diseases, which may increase millions of people add in a vicious cycle of poverty. The study used the number of factors that affect poverty incidence in a panel of 76 countries for a period of 2010-2019. The dynamic panel GMM estimates show that the causes of death by communicable diseases, chemical-induced carbon and fossil fuel combustion, and lack of access to basic hand washing facilities menace to increase poverty headcounts, whereas, an increase in healthcare expenditures substantially decreases poverty headcounts across countries. Further, the results show the U-shaped relationship between economic growth and poverty headcounts, as economic growth first decreases and later increase poverty headcount due to rising healthcare disparities among nations. The causality estimates show that lack of access to basic amenities lead to increase of communicable diseases including COVID-19 whereas chemical-induced carbon and fossil fuel emissions continue to increase healthcare expenditures and economic growth in a panel of selected countries. The rising healthcare disparities, regional conflicts, and public debt burden further 'hold in the hand' of communicable diseases that push millions of people in the poverty trap.", "qid": 19, "docid": "5rzg9iwi", "rank": 85, "score": 7.156700134277344}, {"content": "Title: Does communicable diseases (including COVID-19) may increase global poverty risk? A cloud on the horizon Content: Coronavirus epidemic can push millions of people in poverty. The shortage of healthcare resources, lack of sanitation, and population compactness leads to an increase in communicable diseases, which may increase millions of people add in a vicious cycle of poverty. The study used the number of factors that affect poverty incidence in a panel of 76 countries for a period of 2010\u20132019. The dynamic panel GMM estimates show that the causes of death by communicable diseases, chemical-induced carbon and fossil fuel combustion, and lack of access to basic hand washing facilities menace to increase poverty headcounts, whereas, an increase in healthcare expenditures substantially decreases poverty headcounts across countries. Further, the results show the U-shaped relationship between economic growth and poverty headcounts, as economic growth first decreases and later increase poverty headcount due to rising healthcare disparities among nations. The causality estimates show that lack of access to basic amenities lead to increase of communicable diseases including COVID-19 whereas chemical-induced carbon and fossil fuel emissions continue to increase healthcare expenditures and economic growth in a panel of selected countries. The rising healthcare disparities, regional conflicts, and public debt burden further \u2018hold in the hand\u2019 of communicable diseases that push millions of people in the poverty trap.", "qid": 19, "docid": "zex9rw7n", "rank": 86, "score": 7.156699180603027}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation Content: As the world confronts coronavirus disease 2019 (COVID-19), an illness caused by yet another emerging pathogen (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), obstetric care providers are asking what this means for pregnant women. The global spread has been swift, and many key questions remain. The case-fatality rate for persons cared for in the United States and whether asymptomatic persons transmit the virus are examples of questions that need to be answered to inform public health control measures. There are also unanswered questions specific to pregnant women, such as whether pregnant women are more severely affected and whether intrauterine transmission occurs. Although guidelines for pregnant women from the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have been rapidly developed based on the best available evidence, additional information is critically needed to inform key decisions, such as whether pregnant health care workers should receive special consideration, whether to temporarily separate infected mothers and their newborns, and whether it is safe for infected women to breastfeed. Some current recommendations are well supported, based largely on what we know from seasonal influenza: patients should avoid contact with ill persons, avoid touching their face, cover coughs and sneezes, wash hands frequently, disinfect contaminated surfaces, and stay home when sick. Prenatal clinics should ensure all pregnant women and their visitors are screened for fever and respiratory symptoms, and symptomatic women should be isolated from well women and required to wear a mask. As the situation with COVID-19 rapidly unfolds, it is critical that obstetricians keep up to date.", "qid": 19, "docid": "8patrxld", "rank": 87, "score": 7.091000080108643}, {"content": "Title: Hygienic and ecological risks connected with utilization of animal manures and biosolids in agriculture Content: Abstract In recent years the fate of human and animal pathogen microorganisms as a potential pollutant of the environment has been paid increased attention. Substantial quantities of these compounds and their metabolites are excreted, flushed down the drain, discarded as waste, or left over in animal feedlots. After passing to the sewer, several of these compounds are not adequately eliminated by the methods that are currently used in sewage treatment. Substantial quantities of biosolids and livestock manure end up on agricultural land. Effective sanitation of the environment, particularly of some of its special parts, which can be a source of spreading of diseases, plays an important role in prevention of infectious diseases. In this respect special attention should be paid to the disinfection of infected farm animal excrements. Sanitation of excrements should, on the one hand, ensure effective inhibition of infectious agents and, on the other hand, comply with the requirement of preserving the composition of the manure so it can be used in agricultural production.", "qid": 19, "docid": "mm2o6kr1", "rank": 88, "score": 7.087100028991699}, {"content": "Title: An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes? Content: Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.", "qid": 19, "docid": "sgw0iaz4", "rank": 89, "score": 7.054200172424316}, {"content": "Title: Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane? Content: BACKGROUND AND AIMS: People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS: We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS: Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS: Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.", "qid": 19, "docid": "q1ai1ilp", "rank": 90, "score": 7.041900157928467}, {"content": "Title: Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane? Content: BACKGROUND AND AIMS People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.", "qid": 19, "docid": "y3489g72", "rank": 91, "score": 7.04189920425415}, {"content": "Title: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Content: Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.", "qid": 19, "docid": "bsj7apol", "rank": 92, "score": 7.041299819946289}, {"content": "Title: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Content: Abstract Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.", "qid": 19, "docid": "nserrspn", "rank": 93, "score": 7.041298866271973}, {"content": "Title: Itch in the era of COVID\u201019 pandemic: An unfolding scenario Content: Coronavirus disease 2019 (COVID\u201019) is an infectious disease, caused by severe acute respiratory syndrome (SARS)\u2010CoV\u20102, that broke out in December 2019. In just 4 months it has spread to almost every country in the world and up to April 18, 2020, the virus has infected more than two million people. Itch is the most common symptom in dermatology and a frequent one of systemic diseases. The association of itch and viral diseases has been widely documented; however, the actual prevalence of itch in the patients suffering from new the SARS\u2010CoV\u20102 infection is still unknown. In this paper, we present a review of the available literature on the topic of itch in the affected population. Moreover, we have also analyzed different aspects of itch associated with COVID\u201019 pandemic, not directly related to the viral infection. Those included use of chemicals, hand sanitizers, common use of personal protective equipment and psychosocial stress.", "qid": 19, "docid": "1cwrgdef", "rank": 94, "score": 7.041198253631592}, {"content": "Title: Itch in the era of COVID-19 pandemic: An unfolding scenario Content: Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome (SARS)-CoV-2, that broke out in December 2019. In just 4 months it has spread to almost every country in the world and up to April 18, 2020, the virus has infected more than two million people. Itch is the most common symptom in dermatology and a frequent one of systemic diseases. The association of itch and viral diseases has been widely documented; however, the actual prevalence of itch in the patients suffering from new the SARS-CoV-2 infection is still unknown. In this paper, we present a review of the available literature on the topic of itch in the affected population. Moreover, we have also analyzed different aspects of itch associated with COVID-19 pandemic, not directly related to the viral infection. Those included use of chemicals, hand sanitizers, common use of personal protective equipment and psychosocial stress.", "qid": 19, "docid": "4l5lqjtn", "rank": 95, "score": 7.041197299957275}, {"content": "Title: Environmental perspective of COVID-19 Content: Abstract The outbreak of COVID-19 has caused concerns globally. On 30 January WHO has declared it as a global health emergency. The easy spread of this virus made people to wear a mask as precautionary route, use gloves and hand sanitizer on a daily basis that resulted in generation of a massive amount of medical wastes in the environment. Millions of people have been put on lockdown in order to reduce the transmission of the virus. This epidemic has also changed the people's life style; caused extensive job losses and threatened the sustenance of millions of people, as businesses have shut down to control the spread of virus. All over the world, flights have been canceled and transport systems have been closed. Overall, the economic activities have been stopped and stock markets dropped along with the falling carbon emission. However, the lock down of the COVID-19 pandemic caused the air quality in many cities across the globe to improve and drop in water pollutions in some parts of the world.", "qid": 19, "docid": "j4hnldk4", "rank": 96, "score": 7.041196346282959}, {"content": "Title: Environmental perspective of COVID-19 Content: The outbreak of COVID-19 has caused concerns globally. On 30 January WHO has declared it as a global health emergency. The easy spread of this virus made people to wear a mask as precautionary route, use gloves and hand sanitizer on a daily basis that resulted in generation of a massive amount of medical wastes in the environment. Millions of people have been put on lockdown in order to reduce the transmission of the virus. This epidemic has also changed the people's life style; caused extensive job losses and threatened the sustenance of millions of people, as businesses have shut down to control the spread of virus. All over the world, flights have been canceled and transport systems have been closed. Overall, the economic activities have been stopped and stock markets dropped along with the falling carbon emission. However, the lock down of the COVID-19 pandemic caused the air quality in many cities across the globe to improve and drop in water pollutions in some parts of the world.", "qid": 19, "docid": "z59cvvkf", "rank": 97, "score": 7.041195392608643}, {"content": "Title: COVID-19, chronicle of an expected pandemic Content: What is COVID-19? What are the causes, parameters, and effects of this disease? What are the short- and long-term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.", "qid": 19, "docid": "hf2m7imf", "rank": 98, "score": 7.015900135040283}, {"content": "Title: Environmental contamination of the SARS-CoV-2 in healthcare premises: An urgent call for protection for healthcare workers Content: Importance A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Objective To investigate the extent to which SARS-CoV-2 contaminates healthcare settings, including to identify function zones of the hospital with the highest contamination levels and to identify the most contaminated objects, and personal protection equipment (PPE) in Wuhan, China. Design A field investigation was conducted to collect the surface swabs in various environments in the hospital and a laboratory experiment was conducted to examine the presence of the SARS-CoV-2 RNA. Setting Six hundred twenty-six surface samples were collected within the Zhongnan Medical Center in Wuhan, China in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Participants Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major personal protection equipment (PPE). The SARS-CoV-2 RNAs were detected by reverse transcription-PCR (RT-PCR). Main Outcomes and Measures SARS-CoV-2 RNAs Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects are self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were most contaminated PPE. Conclusions and Relevance Many surfaces were contaminated with SARS-CoV-2 across the hospital in various patient care areas, commonly used objects, medical equipment, and PPE. The 13 hospital function zones were classified into four contamination levels. These findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention precautions among HCWs during the outbreak of COVID-19. The findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2.", "qid": 19, "docid": "rike3ukb", "rank": 99, "score": 6.996200084686279}, {"content": "Title: COVID\u201019, chronicle of an expected pandemic Content: What is COVID\u201019? What are the causes, parameters, and effects of this disease? What are the short\u2010 and long\u2010term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.[Image: see text]", "qid": 19, "docid": "yoy3hj3j", "rank": 100, "score": 6.990200042724609}]}
{"query": "what is the origin of COVID-19", "hits": [{"content": "Title: [What is the origin of SARS-CoV-2?] Content: Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.", "qid": 1, "docid": "dv9m19yk", "rank": 1, "score": 7.285900115966797}, {"content": "Title: Anesthesia and COVID-19: What We Should Know and What We Should Do. Content: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.", "qid": 1, "docid": "0paafp5j", "rank": 2, "score": 6.214600086212158}, {"content": "Title: Anesthesia and COVID-19: What We Should Know and What We Should Do Content: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.", "qid": 1, "docid": "96zsd27n", "rank": 3, "score": 6.214599132537842}, {"content": "Title: Understanding Coronavirus Content: Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience", "qid": 1, "docid": "hmvo5b0q", "rank": 4, "score": 6.16349983215332}, {"content": "Title: Novel Coronavirus (nCoV): a Bitter Old Enemy in a New Avatar Content: Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.", "qid": 1, "docid": "1ij25a7u", "rank": 5, "score": 5.838399887084961}, {"content": "Title: The COVID\u201019 epidemic of manuscripts Content: In the midst of the novel coronavirus pandemic\u2014referred to as COVID\u201019\u2014there has been much uncertainty. We remain uncertain about its precise origin, its structure and composition, how best to test for it, or for resulting immunity, whether or not exposure leads to immunity, whether or not disposable surgical masks are effective, why men and some ethnic minorities are more susceptible and just exactly what the death rate as a result of this virus is. However, one thing is absolutely clear, there has been an epidemic of manuscripts on the subject of COVID\u201019 to nursing journals and, amongst these new manuscripts the rejection rate is, unfortunately, very high.", "qid": 1, "docid": "5d7zien3", "rank": 6, "score": 5.72599983215332}, {"content": "Title: In this issue of Occupational Medicine Content: The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.", "qid": 1, "docid": "xqqn1t4e", "rank": 7, "score": 5.6616997718811035}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 1, "docid": "fqs40ivc", "rank": 8, "score": 5.650400161743164}, {"content": "Title: Novel coronavirus (COVID-19) infection: What a doctor on the frontline needs to know Content: Coronavirus disease 2019 (COVID-19) is a zoonotic respiratory infection originating from Wuhan, China. Rapidly spreading from Wuhan to all inhabited continents of the world, the World Health Organisation declared COVID-19 a pandemic on March 11, 2019. Infected patients present with fever and cough; radiological features include bilateral infiltrates on chest x-ray and computed tomography scanning. Management is supportive with oxygen supplementation, broad-spectrum antibiotics as well as careful fluid balancing. A number of drugs, both new and old, are currently in clinical trials and being used on an experimental basis in clinical practice. The COVID-19 pandemic is the greatest worldwide public health crisis of a generation, and has led to seismic political, economic and social changes. This review provides an overview of COVID-19 for junior doctors who find themselves on a new frontline of healthcare.", "qid": 1, "docid": "iohvj16d", "rank": 9, "score": 5.6381001472473145}, {"content": "Title: The need to manage the risk of thromboembolism in COVID-19 patients Content: COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20(th), 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.", "qid": 1, "docid": "dckuhrlf", "rank": 10, "score": 5.628399848937988}, {"content": "Title: How scientific research reacts to international public health emergencies: a global analysis of response patterns Content: As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.", "qid": 1, "docid": "h4vigeuy", "rank": 11, "score": 5.621099948883057}, {"content": "Title: Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know. Content: OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.", "qid": 1, "docid": "18xs6375", "rank": 12, "score": 5.537600040435791}, {"content": "Title: Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know Content: OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.", "qid": 1, "docid": "sphk023v", "rank": 13, "score": 5.537599086761475}, {"content": "Title: Diagnosing COVID-19: Did We Miss Anything? Content: In late 2019, a mass of patients showing symptoms of a pneumonia-like disease of unknown origin emerged in Wuhan, China. Little did the world know it was the prelude of what would be a devastating pandemic. Samples were collected from these patients and the use of unbiased sequencing, and subsequent isolation of the pathogen using human airway epithelial cells led to the discovery of a novel coronavirus, named 2019-nCoV by the World Health Organization (WHO) and Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The disease caused by this virus is officially called the coronavirus disease 2019 (COVID-19).", "qid": 1, "docid": "fybo3ltn", "rank": 14, "score": 5.504000186920166}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 1, "docid": "41378qru", "rank": 15, "score": 5.461999893188477}, {"content": "Title: COVID\u201019 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS\u2010CoV\u20102, causative agent of COVID\u201019, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID\u201019. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS\u2010CoV\u20102 and discuss the evidence and explications for a disproportionately stronger impact of COVID\u201019 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS\u2010CoV\u20102 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS\u2010CoV\u20102.", "qid": 1, "docid": "ipl6189w", "rank": 16, "score": 5.46199893951416}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of COVID-19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 1, "docid": "l2wzr3w1", "rank": 17, "score": 5.461997985839844}, {"content": "Title: Sweden backcasting, now?-Strategic planning for Covid-19 mitigation in a liberal democracy Content: Sweden is applying the herd-immunity as its main natural science strategy to combat the Covid-19 pandemic. This has been communicated in a transparent manner. Small groups of young(er) people of up to approximately 50 individuals are subject to a bigger risk of infection than others. The objective of this paper is to make a case for the argument, that alongside herd-immunity, Sweden is using the social science originated planning approach: backcasting. The government has not been transparent on backcasting. The authors present the use of backcasting only as an argument based on available data and authors' reasoning. A backcasting exercise for the case of the Swedish economy is constructed. This frame outlines five interdependent levels with which a national economy can apply what this paper calls a backcasting herd-immunity approach in its COVID-19 policy. The authors further suggest how it is possible to use social science, natural science and political ideology as complementary in COVID-19 mitigation in particular and in sustainability strategies in general.", "qid": 1, "docid": "lrlkhr61", "rank": 18, "score": 5.461997032165527}, {"content": "Title: [Left behind populations, COVID-19 and risks of health inequities : a guide of the local social-health network (Vaud, Switzerland)]. Content: Since the emergence of the COVID-19 pandemic, the Confederation has referred to \u00ab vulnerable populations \u00bb over the age of 65 and/or with co-morbidities as potentially at risk. This group should not overshadow other highly vulnerable populations such as forced migrants, people deprived of their liberty, and the homeless. In the context of the current pandemic, there is a risk of increasing inequities in care among these populations. In this practical article, we list the marginalized and disadvantaged left behind populations in the canton of Vaud and the issues of inequities in care in the context of the pandemic; we also present the implementation of procedures sometimes original, always inter-professional and interdisciplinary, specifying who the partners are and what the resources are for front-line caregivers.", "qid": 1, "docid": "02imiypy", "rank": 19, "score": 5.438799858093262}, {"content": "Title: [Left behind populations, COVID-19 and risks of health inequities : a guide of the local social-health network (Vaud, Switzerland)] Content: Since the emergence of the COVID-19 pandemic, the Confederation has referred to \u00ab vulnerable populations \u00bb over the age of 65 and/or with co-morbidities as potentially at risk This group should not overshadow other highly vulnerable populations such as forced migrants, people deprived of their liberty, and the homeless In the context of the current pandemic, there is a risk of increasing inequities in care among these populations In this practical article, we list the marginalized and disadvantaged left behind populations in the canton of Vaud and the issues of inequities in care in the context of the pandemic;we also present the implementation of procedures sometimes original, always inter-professional and interdisciplinary, specifying who the partners are and what the resources are for front-line caregivers", "qid": 1, "docid": "b3ze0726", "rank": 20, "score": 5.438798904418945}, {"content": "Title: Can China return to normalcy while keeping the coronavirus in check? Content: Life is almost back to normal in much of China Shops, restaurants, bars, and offices are open for business Manufacturing activity is picking up Traffic once again jams the highways of major cities Three quarters of China's workforce was back on the job as of 24 March, according to one company\u2019s estimate Wuhan, where the COVID-19 pandemic originated, is lagging, as is the rest of Hubei province\u2014but even there, the lockdown is due to lift 8 April China has done what few believed was possible: bring a blazing epidemic of a respiratory virus to a virtual standstill On 18 March, the country reported zero locally transmitted cases of COVID-19 for the first time Since then, only 6 of such infections have been reported, only one of them in Wuhan Now, the key question is: Can China keep it that way?", "qid": 1, "docid": "qq23ebh0", "rank": 21, "score": 5.375100135803223}, {"content": "Title: COVID-19: a crash test for biomedical publishing? Content: The effect of COVID-19 on biomedical publishing (BP) (i.e. scientific biomedical periodicals continuously published by research communities or commercial publishers) has not been deeply explored. To estimate the immediate COVID-19 impact on BP, we have assessed PubMed-indexed articles about COVID-19 (PMIAC) from December 2019 to April 2020. PMIAC have been classified according to publication date, country, and journals for evaluation of time-, region- and scientometric-dependant impact of COVID-19 on BP and have been curated manually (i.e. each entry has been individually analyzed). PMIAC analysis reflects geographic and temporal parameters of outbreak spread. A major BP problem is related to the fact that only 40% of articles report/review/analyze data. Another BP weakness is the clusterization of \"highly-trusted\" publications according to countries of origin and \"highly impacting\" journals. Finally, a problem highlighted by COVID-19 crisis is the increased specification of biomedical research. To solve the problem, analytical reviews integrating data from different areas of biology and medicine are required. The data on PMIAC suggest priority of \"what is published\" over \"where it is published\" and \"who are the authors\". We believe that our brief analysis may help to shape forthcoming BP to become more effective in solving immediate problems resulted from global threats.", "qid": 1, "docid": "37v59fs8", "rank": 22, "score": 5.372499942779541}, {"content": "Title: Covid\u201019 and neurodegeneration. What can we learn from the past? Content: Coronaviridae (CoVs) are single stranded RNA viruses. \u03b2eta\u2010CoVs encompasses Bat coronavirus (BCoV), the human Severe Acute Respiratory Syndrome (SARS) virus and the Middle Eastern Respiratory Syndrome (MERS) virus. In December 2019, a new \u03b2eta\u2010CoVs was identified in Wuhan, China, SARS\u2010CoV\u20102. The genome sequencing demonstrated a 79.5% and 96.2% identity to SARS\u2010CoV and a bat CoV genome, respectively, supporting the interspecies transmission and the origin of this new pandemia.", "qid": 1, "docid": "30j0auua", "rank": 23, "score": 5.347099781036377}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \u201coriginal antigenic sin.\u201d The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 1, "docid": "7k24r3p5", "rank": 24, "score": 5.344799995422363}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \"original antigenic sin.\" The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 1, "docid": "nacxjt2f", "rank": 25, "score": 5.344799041748047}, {"content": "Title: Data Mining and Content Analysis of the Chinese Social Media Platform Weibo During the Early COVID-19 Outbreak: Retrospective Observational Infoveillance Study Content: BACKGROUND: The coronavirus disease (COVID-19) pandemic, which began in Wuhan, China in December 2019, is rapidly spreading worldwide with over 1.9 million cases as of mid-April 2020. Infoveillance approaches using social media can help characterize disease distribution and public knowledge, attitudes, and behaviors critical to the early stages of an outbreak. OBJECTIVE: The aim of this study is to conduct a quantitative and qualitative assessment of Chinese social media posts originating in Wuhan City on the Chinese microblogging platform Weibo during the early stages of the COVID-19 outbreak. METHODS: Chinese-language messages from Wuhan were collected for 39 days between December 23, 2019, and January 30, 2020, on Weibo. For quantitative analysis, the total daily cases of COVID-19 in Wuhan were obtained from the Chinese National Health Commission, and a linear regression model was used to determine if Weibo COVID-19 posts were predictive of the number of cases reported. Qualitative content analysis and an inductive manual coding approach were used to identify parent classifications of news and user-generated COVID-19 topics. RESULTS: A total of 115,299 Weibo posts were collected during the study time frame consisting of an average of 2956 posts per day (minimum 0, maximum 13,587). Quantitative analysis found a positive correlation between the number of Weibo posts and the number of reported cases from Wuhan, with approximately 10 more COVID-19 cases per 40 social media posts (P<.001). This effect size was also larger than what was observed for the rest of China excluding Hubei Province (where Wuhan is the capital city) and held when comparing the number of Weibo posts to the incidence proportion of cases in Hubei Province. Qualitative analysis of 11,893 posts during the first 21 days of the study period with COVID-19-related posts uncovered four parent classifications including Weibo discussions about the causative agent of the disease, changing epidemiological characteristics of the outbreak, public reaction to outbreak control and response measures, and other topics. Generally, these themes also exhibited public uncertainty and changing knowledge and attitudes about COVID-19, including posts exhibiting both protective and higher-risk behaviors. CONCLUSIONS: The results of this study provide initial insight into the origins of the COVID-19 outbreak based on quantitative and qualitative analysis of Chinese social media data at the initial epicenter in Wuhan City. Future studies should continue to explore the utility of social media data to predict COVID-19 disease severity, measure public reaction and behavior, and evaluate effectiveness of outbreak communication.", "qid": 1, "docid": "18im3npb", "rank": 26, "score": 5.332499980926514}, {"content": "Title: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement Content: With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.", "qid": 1, "docid": "5p0yyrdx", "rank": 27, "score": 5.277699947357178}, {"content": "Title: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement Content: [Image: see text] With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.", "qid": 1, "docid": "kbvy4g7i", "rank": 28, "score": 5.277698993682861}, {"content": "Title: The advantages of the simplest pandemic models Content: As a pandemic of coronavirus spreads across the globe, people debate policies to mitigate its severity. Many complex, highly detailed models have been developed to help policy setters make better decisions. However, the basis of these models is unlikely to be understood by non-experts. We describe the advantages of simple models for covid-19. We say a model is simple if its only parameter is the rate of contact between people in the population. This contact rate can vary over time, depending on choices by policy setters. Such models can be understood by a broad audience, and thus can be helpful in explaining the policy decisions to the public. They can be used to evaluate the outcomes of different policy strategies. However, simple models have a disadvantage when dealing with inhomogeneous populations. To augment the power of a simple model to evaluate complicated situations, we add what we call satellite equations that do not change the original model. For example, with the help of a satellite equation, one could know what his/her chance is of remaining uninfected through the end of epidemic. Satellite equations can model the effect of the epidemic on high-risk individuals, or death rates, or on nursing homes, and other isolated populations. To compare simple models with complex models, we introduce our slightly complex Model J. We find the conclusions of simple and complex models can be quite similar. But, for each added complexity, a modeler may have to choose additional parameter values describing who will infect whom under what conditions, choices for which there is often little rationale but that can have a big impact on predictions. Our simulations suggest that the added complexity offers little predictive advantage.", "qid": 1, "docid": "b4s6mz76", "rank": 29, "score": 5.236100196838379}, {"content": "Title: First impact on services and their preparation. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency Content: This paper reports the immediate impact of the epidemic on rehabilitation services in Italy, the first country in Europe hit by Covid-19. In a country with almost 5,000 Physical and Rehabilitation Medicine physicians, the webinar had 230 live viewers (4.5%), and more than 8,900 individual visualizations of the recorded version. The overall inadequate preparation of the rehabilitation system to face a sudden epidemic was clear, and similar to that of the acute services. The original idea of confining the Covid-19 cases to some areas of rehabilitation wards and/or hospitals, preserving others, proved not to be feasible. Continuous reorganization and adaptation were required due to the rapid changes. Overall, rehabilitation needs had to surrender to the more acute emergency, with total conversion of beds, wards and even hospitals. The quarantine needs heavily involved also outpatient services that were mostly closed. Rehabilitation professionals needed support, but also acted properly, again similarly to what happened in the acute wards. The typical needs of rehabilitation, such as human and physical contacts, but also social interactions including patient, team, family and caregivers, appeared clearly in the current unavoidable need of being suppressed. These notes could serve the preparation of other services worldwide.", "qid": 1, "docid": "aurhahaq", "rank": 30, "score": 5.1981000900268555}, {"content": "Title: First impact on services and their preparation. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency. Content: This paper reports the immediate impact of the epidemic on rehabilitation services in Italy, the first country in Europe hit by Covid-19. In a country with almost 5,000 Physical and Rehabilitation Medicine physicians, the webinar had 230 live viewers (4.5%), and more than 8,900 individual visualizations of the recorded version. The overall inadequate preparation of the rehabilitation system to face a sudden epidemic was clear, and similar to that of the acute services. The original idea of confining the Covid-19 cases to some areas of rehabilitation wards and/or hospitals, preserving others, proved not to be feasible. Continuous reorganization and adaptation were required due to the rapid changes. Overall, rehabilitation needs had to surrender to the more acute emergency, with total conversion of beds, wards and even hospitals. The quarantine needs heavily involved also outpatient services that were mostly closed. Rehabilitation professionals needed support, but also acted properly, again similarly to what happened in the acute wards. The typical needs of rehabilitation, such as human and physical contacts, but also social interactions including patient, team, family and caregivers, appeared clearly in the current unavoidable need of being suppressed. These notes could serve the preparation of other services worldwide.", "qid": 1, "docid": "fpywiwoh", "rank": 31, "score": 5.198099136352539}, {"content": "Title: In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek\u2019s own, and he does not in any way speak for his employer Content: Let\u2019s take inventory on the therapies that are being developed for the coronavirus epidemic Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they\u2019re making all their Covid-19 content free to all readers during this crisis I\u2019d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons The Biocentury list doesn\u2019t cover these, but here\u2019s an article at Nature Biotechnology that goes into detail Clinical trials are a huge time sink \u2013 they sort of have to be, in most cases, if they\u2019re going to be any good \u2013 and if you\u2019ve already done all that stuff it\u2019s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right This has been in development for a few years as an RNA virus therapy \u2013 it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit The compound is a prodrug \u2013 that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524 It mechanism of action is to get incorporated into viral RNA, since it\u2019s taken up by RNA polymerase and it largely seems to evade proofreading This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited", "qid": 1, "docid": "ol0bj3hs", "rank": 32, "score": 5.191100120544434}, {"content": "Title: The SARS-CoV-2 outbreak: What we know Content: Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "qid": 1, "docid": "5fg87lvu", "rank": 33, "score": 5.100800037384033}, {"content": "Title: The SARS-CoV-2 outbreak: What we know Content: There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "qid": 1, "docid": "950x4b9a", "rank": 34, "score": 5.100799083709717}, {"content": "Title: Dermatologists and SARS\u2010CoV\u20102: The impact of the pandemic on daily practice Content: Since the first case of \u201cpneumonia of unknown aetiology\u201d was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as \u201csevere acute respiratory syndrome coronavirus 2\u201d (SARS\u2010CoV\u20102) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease\u201019 (COVID\u2010 19) and satisfying the epidemiological criteria for a label of \u201cpandemic.\u201d The ongoing SARS\u2010CoV\u20102 pandemic is having a huge impact on dermatological practice including the marked reduction of face\u2010to\u2010face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID\u201019 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID\u201019 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS\u2010CoV\u20102 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS\u2010CoV\u20102 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS\u2010CoV\u20102 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID\u201019 disaster. Learning from experience may help to cope with future major societal changes.", "qid": 1, "docid": "erntrh3p", "rank": 35, "score": 5.095399856567383}, {"content": "Title: Dermatologists and SARS-CoV-2: the impact of the pandemic on daily practice Content: Since the first case of 'pneumonia of unknown aetiology' was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognized thereafter as 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) has spread over the four continents, causing the respiratory manifestations of coronavirus disease-19 (COVID-19) and satisfying the epidemiological criteria for a label of 'pandemic'. The ongoing SARS-CoV-2 pandemic is having a huge impact on dermatological practice including the marked reduction of face-to-face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID-19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID-19 care for patient assistance and new research needs to be addressed. It is not known yet if skin lesions and derangement of the skin barrier could make it easier for SARS-CoV-2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS-CoV-2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS-CoV-2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID-19 disaster. Learning from experience may help to cope with future major societal changes.", "qid": 1, "docid": "hl1eq3eb", "rank": 36, "score": 5.095398902893066}, {"content": "Title: The impact of ethnicity on clinical outcomes in COVID-19: A systematic review Content: BACKGROUND: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes. METHODS: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1(st) December 2019-15(th) May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654. FINDINGS: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity \u2013 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups. INTERPRETATION: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance. FUNDING: NIHR", "qid": 1, "docid": "n3d130t8", "rank": 37, "score": 5.092100143432617}, {"content": "Title: Understanding the Anemic Global Response to COVID-19. Content: The COVID-19 outbreak is the most serious test of the international system since the 2008 global financial crisis. Rather than cooperate to contain and respond to a common threat, the world's leading powers, the United States and China, increasingly blamed each other through wildly speculative theories about the origins of the virus. The World Health Organization (WHO) sought to coordinate a global response but it has been hamstrung and come under attack. Given past cooperation between major powers to mobilize and eradicate smallpox and previous U.S. leadership to fight HIV/AIDS and the 2014 West African Ebola crisis, the limited cooperation and lack of leadership are puzzling. What explains the anemic global response to date? This paper draws from structural international relations theory to suggest a partial but somewhat dissatisfying answer. International organizations are inherently weak faced with opposition by major powers. The international system simultaneously incentivizes states to cooperate and address common threats but at the same time encourages countries to take care of themselves, potentially at the expense of others. Which of these motives dominates cannot be explained by structural theory, requiring us to look to other factors such as the attributes of states or of leaders themselves.", "qid": 1, "docid": "1ymp63rl", "rank": 38, "score": 5.078499794006348}, {"content": "Title: Understanding the Anemic Global Response to COVID-19 Content: The COVID-19 outbreak is the most serious test of the international system since the 2008 global financial crisis. Rather than cooperate to contain and respond to a common threat, the world's leading powers, the United States and China, increasingly blamed each other through wildly speculative theories about the origins of the virus. The World Health Organization (WHO) sought to coordinate a global response but it has been hamstrung and come under attack. Given past cooperation between major powers to mobilize and eradicate smallpox and previous U.S. leadership to fight HIV/AIDS and the 2014 West African Ebola crisis, the limited cooperation and lack of leadership are puzzling. What explains the anemic global response to date? This paper draws from structural international relations theory to suggest a partial but somewhat dissatisfying answer. International organizations are inherently weak faced with opposition by major powers. The international system simultaneously incentivizes states to cooperate and address common threats but at the same time encourages countries to take care of themselves, potentially at the expense of others. Which of these motives dominates cannot be explained by structural theory, requiring us to look to other factors such as the attributes of states or of leaders themselves.", "qid": 1, "docid": "wcnzb3o0", "rank": 39, "score": 5.078498840332031}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID\u201019 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID\u201019). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID\u201019 are treated with these agents and more evidence accumulates, there continues to be no high\u2010quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto\u2010immune conditions, and provided a component in the original rationale for their use in patients with COVID\u201019, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID\u201019. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID\u201019, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID\u201019 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case\u2010by\u2010case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 1, "docid": "75vvix5o", "rank": 40, "score": 5.058700084686279}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID-19 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 1, "docid": "87uhx3pt", "rank": 41, "score": 5.058699131011963}, {"content": "Title: Occupational health responses to COVID\u201019: What lessons can we learn from SARS? Content: On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus\u2014SARS\u2010CoV\u20102. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of d\u00e9j\u00e0 vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002\u20102003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case\u2010fatality rate of SARS (9.6%) is higher than that of COVID\u201019 (<4%). Another zoonotic novel coronavirus, MERS\u2010CoV, was responsible for the Middle East respiratory syndrome, which had a case\u2010fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID\u201019, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID\u201019 outbreak.", "qid": 1, "docid": "ib5c3lbi", "rank": 42, "score": 5.0586981773376465}, {"content": "Title: Occupational health responses to COVID-19: What lessons can we learn from SARS? Content: On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus-SARS-CoV-2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of d\u00e9j\u00e0 vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002-2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case-fatality rate of SARS (9.6%) is higher than that of COVID-19 (<4%). Another zoonotic novel coronavirus, MERS-CoV, was responsible for the Middle East respiratory syndrome, which had a case-fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID-19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID-19 outbreak.", "qid": 1, "docid": "tr7h36i9", "rank": 43, "score": 5.05869722366333}, {"content": "Title: Coronavirus-2019. General considerations/ Coronavirus-2019. Consideraciones Generales Content: According to what was published by the WHO (World Health Organization), a first case of acute respiratory infection, of unknown origin, appeared in the province of HUBEI, CHINA, in the city of WUHAN, (December 2019). After having ruled out other etiological agents, the isolation of a new coronavirus (7-01-2020) was achieved, which was called new coronavirus (nCOV, COVID-19), currently named SARS-CoV-2. Coronaviruses, being important pathogens, can infect the respiratory, gastrointestinal, hepatic, and nervous systems of humans and birds, livestock, bats, mice, and other wild animals. Since the outbreaks of SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle East Respiratory Syndrome) in 2012, the transmission of these viruses between humans and animals has been demonstrated.", "qid": 1, "docid": "n6jgr1kx", "rank": 44, "score": 5.034599781036377}, {"content": "Title: Is the kidney a target of SARS-CoV-2? Content: The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.", "qid": 1, "docid": "48wy2iqx", "rank": 45, "score": 5.023200035095215}, {"content": "Title: Left behind populations, COVID-19 and risks of health inequities : a guide of the local social-health network (Vaud, Switzerland)/ Populations precarisees, COVID-19 et risques diniquites en sante : guide du reseau socio-sanitaire vaudois Content: Since the emergence of the COVID-19 pandemic, the Confederation has referred to vulnerable populations over the age of 65 and/or with co-morbidities as potentially at risk This group should not overshadow other highly vulnerable populations such as forced migrants, people deprived of their liberty, and the homeless In the context of the current pandemic, there is a risk of increasing inequities in care among these populations In this practical article, we list the marginalized and disadvantaged left behind populations in the canton of Vaud and the issues of inequities in care in the context of the pandemic;we also present the implementation of procedures sometimes original, always inter-professional and interdisciplinary, specifying who the partners are and what the resources are for front-line caregivers Depuis lapparition de la pandemie du COVID-19, la Confederation evoque comme potentiellement a risque les populations vulnerables de plus de 65 ans et/ou presentant des comorbidites Ce groupe ne doit pas eclipser dautres populations en situation de grande vulnerabilite telles que les personnes issues de la migration forcee, celles privees de liberte, ainsi que les sans domicile fixe Dans cet article qui se veut pratique, nous enumerons differentes populations marginalisees du canton de Vaud et les enjeux diniquites dans les soins dans le cadre de la pandemie ;nous presentons egalement limplementation de procedures, parfois originales, toujours interprofessionnelles et interdisciplinaires, en precisant qui sont les partenaires et quelles sont les ressources pour les soignants de premiere ligne", "qid": 1, "docid": "p2i0ha2u", "rank": 46, "score": 4.880899906158447}, {"content": "Title: The EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) initiative: background and protocol for the international SARS-CoV-2 infections registry Content: The outbreak of SARS-CoV-2 is the worst healthcare emergency of this century, and its impact on pediatrics and neonatology is still largely unknown. The European Society for Pediatric and Neonatal Intensive Care (ESPNIC) launched the EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) international, multicenter, and multidisciplinary initiative to study the epidemiology, clinical course, and outcomes of pediatric and neonatal SARS-CoV-2 infections. EPICENTRE background and aims are presented together with protocol details. EPICENTRE is open to centers all over the world, and this will allow to provide a pragmatic picture of the epidemic, with a particular attention to pediatric and neonatal critical care issues.Conclusions: EPICENTRE will allow researchers to clarify the epidemiology, clinical presentation, and outcomes of pediatric and neonatal SARS-CoV-2 infection, refining its clinical management and hopefully providing new insights for clinicians. What is Known: \u00e2\u0080\u00a2 COVID19 is the new disease caused by SARS-CoV-2 infection and is spreading around the globe. \u00e2\u0080\u00a2 Majority of data available about SARS-CoV-2 infections originates from adult patients. What is New: \u00e2\u0080\u00a2 EPICENTRE is the first international, multicenter, multidisciplinary, meta-data driven, hospital-based, online, prospective cohort registry dedicated to neonatal and pediatric SARS-CoV-2 infections. \u00e2\u0080\u00a2 EPICENTRE will allow to understand epidemiology and physiopathology of COVID19.", "qid": 1, "docid": "pzf6a26k", "rank": 47, "score": 4.87060022354126}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 1, "docid": "kgifmjvb", "rank": 48, "score": 4.8592000007629395}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country\u2019s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world\u2019s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada\u2019s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 1, "docid": "wmfcey6f", "rank": 49, "score": 4.859199047088623}, {"content": "Title: Early Stage Prediction of US County Vulnerability to the COVID-19 Pandemic Content: Key Points: Question: What are key factors that define the vulnerability of counties in the US to cases of the COVID-19 virus? Findings: In this epidemiological study based on publicly available data, we develop a model that predicts vulnerability to COVID-19 for each US county in terms of likelihood of going from no documented cases to at least one case within five days and in terms of number of occurrences of the virus. Meaning: Predicting county vulnerability to COVID-19 can assist health organizations to better plan for resource and workforce needs. Abstract Importance: The rapid spread of COVID-19 means that government and health services providers have little time to plan and design effective response policies. It is therefore important to rapidly provide accurate predictions of how vulnerable geographic regions such as counties are to the spread. Objective: Developing county level prediction around near future disease movement for COVID-19 occurrences using publicly available data. Design: Original Investigation; Decision Analytical Model Study for County Level COVID-19 occurrences using data from March 14-31, 2020. Setting: Disease spread prediction for US counties. Participants: All US county level granularity based on data fused from multiple publicly available sources inclusive of health statistics, demographics, and geographical features. Exposure(s) (for observational studies): Daily county level reported COVID-19 occurrences from March 14-31, 2020. Main Outcome(s) and Measure(s): We developed a 3-stage model to quantify, firstly the probability of COVID-19 occurrence for unaffected counties using XGBoost classifier and secondly, the number of potential occurrences of a county via XGBoost regression. Thirdly, these results are combined to compute the county level risk. This risk is then used as an estimated after-five-day-vulnerability of the county. Results: Using data from March 14-31, 2020, the model shows a sensitivity over 71.5% and specificity over 94%. Conclusions and Relevance: We found that population, population density, percentage of people aged 70 or greater and prevalence of comorbidities play an important role in predicting COVID-19 occurrences. We found a positive association between affected and urban counties as well as less vulnerable and rural counties. The developed model can be used for identification of vulnerable counties and potential data discrepancies. Limited testing facilities and delayed results introduces significant variation in reported cases and produces a bias in the model. Trial Registration: Not Applicable", "qid": 1, "docid": "901ghexi", "rank": 50, "score": 4.850299835205078}, {"content": "Title: Coronaviruses pandemics: Can neutralizing antibodies help? Content: For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not \"to be or not to be\" yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.", "qid": 1, "docid": "ad6ztoba", "rank": 51, "score": 4.845699787139893}, {"content": "Title: Dynamic causal modelling of COVID-19 Content: This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process.", "qid": 1, "docid": "bfnav9sn", "rank": 52, "score": 4.845698833465576}, {"content": "Title: Coronaviruses pandemics: Can neutralizing antibodies help? Content: For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not \u201cto be or not to be\u201d yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.", "qid": 1, "docid": "qhelk6u6", "rank": 53, "score": 4.84569787979126}, {"content": "Title: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.", "qid": 1, "docid": "safr9z37", "rank": 54, "score": 4.811500072479248}, {"content": "Title: Continuity of Constitutional Government during a Pandemic: Considering the Concept in Canada's Emergency Management Act Content: This research note examines the undefined meaning of the government's obligations to ensure \u201ccontinuity of constitutional government\u201d (CCG) as provided for in section 4(l) of the Emergency Management Act, S.C. 2007, c. 15 (Canada, 2007). Specifically, that section gives the minister of public safety and emergency preparedness the responsibility for \u201cestablishing the necessary arrangements for the continuity of constitutional government in the event of an emergency,\u201d but the term is itself undefined. The article will canvass the origin of the term and its relationship to other so-called continuity of government (COG) concepts, along with some legal written opinion on what the term might in practice mean, should the minister ever be charged with discharging this responsibility. It will conclude with some final thoughts on the relevance of the CCG concept to the current pandemic. Given that the COVID-19 virus has infected Sophie Gr\u00e9goire Trudeau, the prime minister's wife, forced a drastically reduced and possibly \u201cvirtual\u201d federal Parliament, placed the British prime minister in intensive care and led to the self-isolation of many world leaders, the topic is relevant to Canada in 2020.", "qid": 1, "docid": "26276rpr", "rank": 55, "score": 4.785900115966797}, {"content": "Title: The influence of comorbidity on the severity of COVID-19 disease: systematic review and analysis Content: A novel form of coronavirus disease (SARS-CoV-2) has spread rapidly across the world. This disease, originating in Wuhan, China, has become a global pandemic. What risk factors influence the severity of the disease is of considerable importance. This research is intended to offer a systematic review/meta-analysis for assessing how common clinical conditions and comorbidities correlate with COVID-19. The meta-analysis incorporated seven studies covering 4101 COVID-19 patients from Chinese hospitals who had their diagnosis confirmed through laboratory testing. The findings demonstrate that the most common comorbidities with the disease were COPD (2.53%, OR 3.24 [95% CI: 1.99-4.45], p< 0.0006), cardiovascular disease (10.76%, OR 2.89 [95% CI: 1.90-4.40], p <0.0001), coronary heart disease (5.52%, OR 2.97 [95% CI: 1.99-4.45], p <0.0001), diabetes (11.34%, OR 2.27, [95% CI: 1.46-3.53], p = 0.0003), and hypertension (22.07%, OR 2.43 [95% CI: 1.71-3.45], p <0.0001). No significant associations were found for disease severity with the comorbidities of kidney disease, liver disease, or cancer. The most frequently exhibited clinical symptoms were fever (74.52%, OR 1.37, 95% CI: 1.01-1.86, p = 0.04), cough (62.15%, OR 1.25, 95% CI: 0.97-1.60, p = 0.0823), myalgia/fatigue (38.77%, OR 1.31, 95% CI: 1.11-1.55, p = 0.0018), dyspnea (33.9%, OR 3.61, 95% CI: 2.57-5.06, p = <0.0001), respiratory failure/ARDS (20.6%, OR 11.46, 95% CI: 3.24-40.56, p = 0.0002), diarrhea (11.21%) and chest tightness/pain (16.82%, OR 2.17, 95% CI: 1.40-3.36, p = 0.0006). Meta-analysis also revealed that neither the duration of the incubation period nor current smoking status associated with disease severity.", "qid": 1, "docid": "5vpnmw3f", "rank": 56, "score": 4.764900207519531}, {"content": "Title: Pigs, Poultry, and Pandemic Influenza: How Zoonotic Pathogens Threaten Human Health Content: Emerging infections have an enormous impact on human health, food supply, economics, and the environment. Animals, and wild animals in particular, are considered to be the source of more than 70% of all emerging infections in humans. Two zoonotic influenza viruses that successfully spread from animals to humans are highly pathogenic avian influenza (HPAI) H5N1 virus, originating from poultry, and pandemic H1N1 influenza (pH1N1) virus, thought to originate from domestic swine. In this review, we discuss our research on the host species barrier for these viruses, concentrating on three questions: how does HPAI H5N1 virus transmit from birds to humans; what are the within-host dynamics of HPAI H5N1 virus and pH1N1 virus in humans and other mammals; and what determines transmission of influenza viruses among humans. To contain and eradicate zoonotic influenza viruses requires not only strategic virus surveillance of both animal and human populations, but also a better understanding of the hurdles that such a virus needs to jump over in order to cross the species barrier and cause a human pandemic. Advances in these two areas will allow us to better predict the risk of emergence of zoonotic influenza viruses in the human population.", "qid": 1, "docid": "ipdyywbx", "rank": 57, "score": 4.757199764251709}, {"content": "Title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence Content: Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.", "qid": 1, "docid": "4dtk1kyh", "rank": 58, "score": 4.7378997802734375}, {"content": "Title: A Genomic Perspective on the Origin and Emergence of SARS-CoV-2 Content: The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.", "qid": 1, "docid": "5hio4lgc", "rank": 59, "score": 4.728400230407715}, {"content": "Title: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far Content: In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.", "qid": 1, "docid": "ldklj4oz", "rank": 60, "score": 4.727499961853027}, {"content": "Title: What do we know about COVID-19? A review article Content: OBJECTIVES: To bring summarized information about what has been published so far regarding Covid-19, facilitating the access to information and a better understanding of this pandemic, and to contribute to the medical community in the decision-making against this virus METHODS: This review article brings collected information from different articles published since the beginning of the pandemic of the 2019 novel coronavirus KEY RESULTS: This paper aggregates and consolidates some epidemiological parameters and clinical knowledge about the novel coronavirus and brings what is new in the search for pandemic control MAJOR CONCLUSIONS: Governments and health authorities are under increased pressure to control the COVID-19 spreading In this scenario, the scientific community is working hard to produce relevant papers which will help in the next steps against coronavirus Our review summarized the latest news about SARS-CoV2, evidencing what we know about COVID-19 until now", "qid": 1, "docid": "55dihml5", "rank": 61, "score": 4.715199947357178}, {"content": "Title: COVID-19: What Should Interventional Radiologists Know and What Can They Do? Content: The outbreak of coronavirus disease 2019 (COVID-19) in late December 2019 in Wuhan, China, has been characterized as a \u201cpandemic\u201d by the World Health Organization and has resulted in 81,603 confirmed cases in China, among the 334,981 cases confirmed in 189 countries as of 09:00 am, March 24, 2020 (China central standard time). During the past 3 months, hundreds of thousands of Chinese health care workers, including interventional radiologists (IRs), have been fighting this battle against the horrifying COVID-19 disease. As IRs, what should we know and what can we do when facing this challenge? This paper shares the experience we have gone through.", "qid": 1, "docid": "1915kvwk", "rank": 62, "score": 4.6915998458862305}, {"content": "Title: COVID-19: What Should Interventional Radiologists Know and What Can They Do? Content: The outbreak of coronavirus disease 2019 (COVID-19) in late December 2019 in Wuhan, China, has been characterized as a \"pandemic\" by the World Health Organization and has resulted in 81,603 confirmed cases in China, among the 334,981 cases confirmed in 189 countries as of 09:00 am, March 24, 2020 (China central standard time). During the past 3 months, hundreds of thousands of Chinese health care workers, including interventional radiologists (IRs), have been fighting this battle against the horrifying COVID-19 disease. As IRs, what should we know and what can we do when facing this challenge? This paper shares the experience we have gone through.", "qid": 1, "docid": "rsjvuumi", "rank": 63, "score": 4.691598892211914}, {"content": "Title: The WetNet: What the Oral Polio Vaccine Hypothesis Exposes about Globalized Interspecies Fluid Bonds Content: The author analyzes the aftermath of Edward Hooper's suggestion that the trial of an oral polio vaccine (OPV) in the Belgian colonies of Africa engendered the pandemic form of the AIDS virus, HIV-1. In response to Hooper's book, The River (1999), the Royal Society in London held a conference to debate the origins of HIV. Examination of the quick dismissal of the OPV theory opens a space for legitimately challenging the widely held belief that the vaccine contamination question was convincingly resolved. This article interrogates the relationship between historiography and the making of scientific facts and history, suggesting that historians have been too credulous of scientists' testimony. The further result of the lack of a thorough analysis of the evidence backing the OPV hypothesis has resulted in a missed opportunity to read The River as one of the few detailed accounts of the immense social, political, technological, and interspecies infrastructure constituted by Cold War vaccine production. This biomedical infrastructure dramatically changed the geographic and interspecies mobility of viruses in ways that may be impossible to reconstruct. Yet these potential transmission routes remain crucial to acknowledge. The COVID-19 pandemic draws attention to the critical importance of studying The WetNet, a concept coined by the author to name the conceptual and material infrastructures of inter- and intraspecies fluid bonding.", "qid": 1, "docid": "6c8f3yhz", "rank": 64, "score": 4.670599937438965}, {"content": "Title: The WetNet: What the Oral Polio Vaccine Hypothesis Exposes about Globalized Interspecies Fluid Bonds. Content: The author analyzes the aftermath of Edward Hooper's suggestion that the trial of an oral polio vaccine (OPV) in the Belgian colonies of Africa engendered the pandemic form of the AIDS virus, HIV-1. In response to Hooper's book, The River (1999), the Royal Society in London held a conference to debate the origins of HIV. Examination of the quick dismissal of the OPV theory opens a space for legitimately challenging the widely held belief that the vaccine contamination question was convincingly resolved. This article interrogates the relationship between historiography and the making of scientific facts and history, suggesting that historians have been too credulous of scientists' testimony. The further result of the lack of a thorough analysis of the evidence backing the OPV hypothesis has resulted in a missed opportunity to read The River as one of the few detailed accounts of the immense social, political, technological, and interspecies infrastructure constituted by Cold War vaccine production. This biomedical infrastructure dramatically changed the geographic and interspecies mobility of viruses in ways that may be impossible to reconstruct. Yet these potential transmission routes remain crucial to acknowledge. The COVID-19 pandemic draws attention to the critical importance of studying The WetNet, a concept coined by the author to name the conceptual and material infrastructures of inter- and intraspecies fluid bonding.", "qid": 1, "docid": "eud0mawv", "rank": 65, "score": 4.670598983764648}, {"content": "Title: Pandemic response lessons from influenza H1N1 2009 in Asia Content: During April 2009, a novel H1N1 influenza A virus strain was identified in Mexico and the USA. Within weeks the virus had spread globally and the first pandemic of the 21st Century had been declared. It is unlikely to be the last and it is crucial that real lessons are learned from the experience. Asia is considered a hot spot for the emergence of new pathogens including past influenza pandemics. On this occasion while preparing for an avian, highly virulent influenza virus (H5N1 like) originating in Asia in fact the pandemic originated from swine, and was less virulent. This discrepancy between what was planned for and what emerged created its own challenges. The H1N1 pandemic has tested national health\u2010care infrastructures and exposed shortcomings in our preparedness as a region. Key health challenges include communication throughout the region, surge capacity, access to reliable information and access to quality care, health\u2010care worker skills, quality, density and distribution, access to essential medicines and lack of organizational infrastructure for emergency response. Despite years of preparation the public health and clinical research community were not ready to respond and opportunities for an immediate research response were missed. Despite warm words and pledges efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. This manuscript with authors from across the region describes some of the major challenges faced by Asia in response to the pandemic and draws lessons for the future.", "qid": 1, "docid": "3emzk5by", "rank": 66, "score": 4.645899772644043}, {"content": "Title: COVID-19, chronicle of an expected pandemic Content: What is COVID-19? What are the causes, parameters, and effects of this disease? What are the short- and long-term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.", "qid": 1, "docid": "hf2m7imf", "rank": 67, "score": 4.5903000831604}, {"content": "Title: COVID\u201019, chronicle of an expected pandemic Content: What is COVID\u201019? What are the causes, parameters, and effects of this disease? What are the short\u2010 and long\u2010term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.[Image: see text]", "qid": 1, "docid": "yoy3hj3j", "rank": 68, "score": 4.577600002288818}, {"content": "Title: COVID-19 and myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimising risk of contracting coronavirus disease 2019 (COVID-19) and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post-pandemic environment, the treatment delivered to patients could be more cost-effective and better tailored than before. Healthcare delivery post-COVID-19 will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 1, "docid": "sexx9196", "rank": 69, "score": 4.575799942016602}, {"content": "Title: What\u2019s New With the Old Coronaviruses? Content: Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the \u201ccommon cold.\u201d Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.", "qid": 1, "docid": "1o2ynvy3", "rank": 70, "score": 4.564199924468994}, {"content": "Title: What's New With the Old Coronaviruses? Content: Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the \"common cold.\" Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.", "qid": 1, "docid": "vzmku0vv", "rank": 71, "score": 4.564198970794678}, {"content": "Title: Potential of age distribution profiles for the prediction of COVID-19 infection origin in a patient group Content: The COVID-19 pandemic is a serious and global public health concern. It is now well known that COVID-19 cases may result in mild symptoms leading to patient recovery. However, severity of infection, fatality rates, and treatment responses across different countries, age groups, and demographic groups suggest that the nature of infection is diverse, and a timely investigation of the same is needed for evolving sound treatment and preventive strategies. This paper reports an the analysis of age distribution patterns in six groups of Indian COVID-19 patient populations based on their likely geographical origin of infection viz. the United Kingdom, North America, the European Union, the Middle East, and Asian countries. It was observed that patient groups stratified in this way had a distinct age profile and that some of these groups e.g. patient groups from Asia, the European Union, and the United Kingdom formed a different cluster than those from North America, the Middle East, and other regions. Patient age profiles of a population were found to be highly predictive of the group they belong to, and there are indications of their distinct recovery and fatality rates across gender. Altogether this study provides a scalable framework to estimate the source of infection in a new population of COVID-19 patients with unknown origin. It is also concluded that greater public availability of age and other demographic profile details of patients may be helpful in gaining robust insights into COVID-19 infection origins. Datasets and scripts used in this work are shared at http://covid.sciwhylab.org.", "qid": 1, "docid": "0m5mc320", "rank": 72, "score": 4.547800064086914}, {"content": "Title: Public Health Responses to COVID-19 Outbreaks on Cruise Ships \u2014 Worldwide, February\u2013March 2020 Content: What is already known about this topic? Cruise ships are often settings for outbreaks of infectious diseases because of their closed environment and contact between travelers from many countries What is added by this report? More than 800 cases of laboratory-confirmed COVID-19 cases occurred during outbreaks on three cruise ship voyages, and cases linked to several additional cruises have been reported across the United States Transmission occurred across multiple voyages from ship to ship by crew members;both crew members and passengers were affected;10 deaths associated with cruise ships have been reported to date What are the implications for public health practice? Outbreaks of COVID-19 on cruise ships pose a risk for rapid spread of disease beyond the voyage Aggressive efforts are required to contain spread All persons should defer all cruise travel worldwide during the COVID-19 pandemic", "qid": 1, "docid": "9b6j5lk0", "rank": 73, "score": 4.52269983291626}, {"content": "Title: Federal Public Health Law Content: This chapter explains the origins and current operations of public health emergency law, at both the federal and state levels. When the colonies first formed the United States, there was no national public health law. In a time when traveling any significant distance was rare, infectious disease outbreaks and epidemics were often localized, to an extent that is difficult to imagine today. The origin of independent federal public health authority derives from laws designed to provide medical care for eighteenth-century merchant seamen, a group who traveled constantly and often had little access to care when they became ill in unfamiliar cities. Moreover, their illnesses threatened the mercantile trade that was essential to the economy of the fledging nation. The origins of what is now the U.S. Public Health Service (PHS) began in 1798, when Congress established a fund to provide treatment for sick and injured merchant seamen. The PHS is now a component of the U.S. Department of Health and Human Services (DHHS). The core of federal public health law is found in the statutes that grant authority for various actions to DHHS, PHS, and CDC.", "qid": 1, "docid": "wh41wczp", "rank": 74, "score": 4.51800012588501}, {"content": "Title: COVID-19 and the clinical hematology laboratory Content: The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.", "qid": 1, "docid": "deee71uw", "rank": 75, "score": 4.51639986038208}, {"content": "Title: COVID\u201019 and the clinical hematology laboratory Content: The ongoing COVID\u201019 pandemic originated in Wuhan, Hubei Province, China in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID\u201019 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID\u201019 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory\u2019s role in the diagnosis of COVID\u201019 infection 3) summarize the current state of biomarker analysis in COVID\u201019 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID\u201019 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.", "qid": 1, "docid": "wco27nop", "rank": 76, "score": 4.516398906707764}, {"content": "Title: Covid\u201019 and Myeloma: what are the implications for now and in the future? Content: The pandemic has affected every aspect of myeloma care. Immediate focus is minimizing risk of contracting COVID\u201019 and the sequelae of infection. However, what does the future hold for our patients? What lessons will be taken forward to tackle myeloma in the fiscally constrained future? If we embrace the challenges that will emerge in the post\u2010pandemic environment, the treatment delivered to patients could be more cost effective and better tailored than before. Healthcare delivery post\u2010COVID will not return to how it was, and now is the time to invest in novel strategies to deliver the best possible outcomes for patients.", "qid": 1, "docid": "njg0ln33", "rank": 77, "score": 4.513999938964844}, {"content": "Title: On the sensitivity of non-pharmaceutical intervention models for SARS-CoV-2 spread estimation Content: Introduction: A series of modelling reports that quantify the effect of non pharmaceutical interventions (NPIs) on the spread of the SARS-CoV-2 virus have been made available prior to external scientific peer-review. The aim of this study was to investigate the method used by the Imperial College COVID-19 Research Team (ICCRT) for estimation of NPI effects from the system theoretical viewpoint of model identifiability. Methods: An input-sensitivity analysis was performed by running the original software code of the systems model that was devised to estimate the impact of NPIs on the reproduction number of the SARS-CoV-2 infection and presented online by ICCRT in Report 13 on March 30 2020. An empirical investigation was complemented by an analysis of practical parameter identifiability, using an estimation theoretical framework. Results: Despite being simplistic with few free parameters, the system model was found to suffer from severe input sensitivities. Our analysis indicated that the model lacks practical parameter identifiability from data. The analysis also showed that this limitation is fundamental, and not something readily resolved should the model be driven with data of higher reliability. Discussion: Reports based on system models have been instrumental to policymaking during the SARS-CoV-2 pandemic. With much at stake during all phases of a pandemic, we conclude that it is crucial to thoroughly scrutinise any SARS-CoV-2 effect analysis or prediction model prior to considering its use as decision support in policymaking. The enclosed example illustrates what such a review might reveal.", "qid": 1, "docid": "2zkrbjqe", "rank": 78, "score": 4.507599830627441}, {"content": "Title: The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms Content: The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.", "qid": 1, "docid": "utsr0zv7", "rank": 79, "score": 4.503399848937988}, {"content": "Title: What about the original antigenic sin of the humans versus SARS-CoV-2? Content:", "qid": 1, "docid": "h4gi99hn", "rank": 80, "score": 4.495500087738037}, {"content": "Title: Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics Content: What is COVID-19? Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. What are the goals of this investigation? This study explains the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths and suggests general lessons learned for a strategy to cope with future epidemics similar to COVID-19 to reduce viral infectivity and negative impacts in economic systems and society. What are the results of this study? The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. What is a socioeconomic strategy to prevent future epidemics similar to COVID-19? Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. This study must conclude that a strategy to prevent future epidemics similar to COVID 19 has also to be designed in environmental and sustainability science and not only in terms of biology.", "qid": 1, "docid": "lhd0jn0z", "rank": 81, "score": 4.484499931335449}, {"content": "Title: Contamination and infection: what the coronavirus pandemic could reveal about the evolutionary origins of obsessive-compulsive disorder Content:", "qid": 1, "docid": "alx5uc95", "rank": 82, "score": 4.470200061798096}, {"content": "Title: Contamination and infection: What the coronavirus pandemic could reveal about the evolutionary origins of obsessive-compulsive disorder Content:", "qid": 1, "docid": "vq4t53l9", "rank": 83, "score": 4.470199108123779}, {"content": "Title: The Origin and Prevention of Pandemics Content: Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change and communication strategies. Since there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.", "qid": 1, "docid": "fk60pph3", "rank": 84, "score": 4.465199947357178}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 1, "docid": "x82yaoxc", "rank": 85, "score": 4.4644999504089355}, {"content": "Title: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study Content: To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P < .05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of \u22655 were more frequent in group A than in group B (all P-values < .01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.", "qid": 1, "docid": "g8rsiiy7", "rank": 86, "score": 4.453199863433838}, {"content": "Title: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study Content: To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P\u00e2\u0080\u008a<\u00e2\u0080\u008a.05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of &#8805;5 were more frequent in group A than in group B (all P-values\u00e2\u0080\u008a<\u00e2\u0080\u008a.01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.", "qid": 1, "docid": "m9fikesi", "rank": 87, "score": 4.4531989097595215}, {"content": "Title: Urban Scaling of COVID-19 epidemics Content: Susceptible-Invective-Recovered (SIR) mathematical models are in high demand due to the COVID-19 pandemic. They are used in their standard formulation, or through the many variants, trying to fit and hopefully predict the number of new cases for the next days or weeks, in any place, city, or country. Such is key knowledge for the authorities to prepare for the health systems demand or to apply restrictions to slow down the infectives curve. Even when the model can be easily solved ---by the use of specialized software or by programming the numerical solution of the differential equations that represent the model---, the prediction is a non-easy task, because the behavioral change of people is reflected in a continuous change of the parameters. A relevant question is what we can use of one city to another; if what happened in Madrid could have been applied to New York and then, if what we have learned from this city would be of use for S\\~ao Paulo. With this idea in mind, we present an analysis of a spreading-rate related measure of COVID-19 as a function of population density and population size for all US counties, as long as for Brazilian cities and German cities. Contrary to what is the common hypothesis in epidemics modeling, we observe a higher {\\em per-capita} contact rate for higher city's population density and population size. Also, we find that the population size has a more explanatory effect than the population density. A contact rate scaling theory is proposed to explain the results.", "qid": 1, "docid": "1ttt1fgr", "rank": 88, "score": 4.451300144195557}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: Background: This study\u2019s aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \u201cWhat are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\u201d Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 1, "docid": "irocv0ke", "rank": 89, "score": 4.45129919052124}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: BACKGROUND: This study's aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. METHODS: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \"What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\" RESULTS: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. CONCLUSIONS: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 1, "docid": "o7ze1myf", "rank": 90, "score": 4.451298236846924}, {"content": "Title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID-19: Meta-analysis and sensitivity analysis Content: The coronavirus disease-2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscript conducts a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% CI (2.41-3.90), the average incubation time to be 5.08 days with the 95% CI (4.77-5.39) (in day), the asymptomatic infection rate to be 46% with the 95% CI (18.48%-73.60%), and the case fatality rate to be 2.72% with 95% CI (1.29%-4.16%) where asymptomatic infections are accounted for.", "qid": 1, "docid": "dt0b87me", "rank": 91, "score": 4.44980001449585}, {"content": "Title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID\u201019: Meta\u2010analysis and sensitivity analysis Content: The coronavirus disease\u20102019 (COVID\u201019) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102). However, comprehensive knowledge of COVID\u201019 remains incomplete and many important features are still unknown. This manuscript conducts a meta\u2010analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% CI (2.41\u20103.90), the average incubation time to be 5.08 days with the 95% CI (4.77\u20105.39) (in day), the asymptomatic infection rate to be 46% with the 95% CI (18.48%\u201073.60%), and the case fatality rate to be 2.72% with 95% CI (1.29%\u20104.16%) where asymptomatic infections are accounted for.", "qid": 1, "docid": "fraczoxu", "rank": 92, "score": 4.449799060821533}, {"content": "Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "qid": 1, "docid": "5zb96j4a", "rank": 93, "score": 4.44789981842041}, {"content": "Title: Google Dataset Search by the Numbers Content: Scientists, governments, and companies increasingly publish datasets on the Web. Google's Dataset Search extracts dataset metadata -- expressed using schema.org and similar vocabularies -- from Web pages in order to make datasets discoverable. Since we started the work on Dataset Search in 2016, the number of datasets described in schema.org has grown from about 500K to almost 30M. Thus, this corpus has become a valuable snapshot of data on the Web. To the best of our knowledge, this corpus is the largest and most diverse of its kind. We analyze this corpus and discuss where the datasets originate from, what topics they cover, which form they take, and what people searching for datasets are interested in. Based on this analysis, we identify gaps and possible future work to help make data more discoverable.", "qid": 1, "docid": "95o2v09d", "rank": 94, "score": 4.446000099182129}, {"content": "Title: What might the future bring? COVID-19 planning considerations for faculty and universities Content: This paper applies a scenario planning approach, to outline some current uncertainties related to COVID-19 and what they might mean for plausible futures for which we should prepare, and to identify factors that we as individual faculty members and university institutions should be considering now, when planning for the future under COVID-19. Although the contextual focus of this paper is Canada, the content is likely applicable to other places where the COVID-19 epidemic curve is in its initial rising stage, and where universities are predominantly publicly funded institutions.", "qid": 1, "docid": "mhnm4zac", "rank": 95, "score": 4.4166998863220215}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 1, "docid": "gnaubzah", "rank": 96, "score": 4.411300182342529}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 1, "docid": "hlhhvmtu", "rank": 97, "score": 4.411299228668213}, {"content": "Title: Global academic response to COVID\u201019: Cross\u2010sectional study Content: This study explores the response to COVID\u201019 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross\u2010sectional bibliometric review of COVID\u201019 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission\u2010to\u2010acceptance time and availability of original data. Publisher\u2010responsiveness was assessed by measuring the acceptance\u2010to\u2010publication time and the provision of open access. Three hundred and ninety\u2010eight of 2,835 COVID\u201019 and 55 of 1,513 MERS search results were eligible. Most COVID\u201019 studies were clinical reports (n = 242; 60.8%). The submission\u2010to\u2010acceptance [median: 5 days (IQR: 3\u201311) versus 71.5 days (38\u2013106); P < .001] and acceptance\u2010to\u2010publication [median: 5 days (IQR: 2\u20138) versus 22.5 days (4\u201348\u00b75\u2010; P < .001] times were strikingly shorter for COVID\u201019. Almost all COVID\u201019 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open\u2010access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID\u201019 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one\u2010in\u2010four were published alongside original data, which is a key target for improvement.", "qid": 1, "docid": "vq3axp9l", "rank": 98, "score": 4.402200222015381}, {"content": "Title: COVID-19 Pandemic: What Every Otolaryngologist-Head and Neck Surgeon Needs to Know for Safe Airway Management Content: The novel coronavirus disease 2019 (COVID-19) pandemic has unfolded with remarkable speed, posing unprecedented challenges for health care systems and society. Otolaryngologists have a special role in responding to this crisis by virtue of expertise in airway management. Against the backdrop of nations struggling to contain the virus's spread and to manage hospital strain, otolaryngologists must partner with anesthesiologists and front-line health care teams to provide expert services in high-risk situations while reducing transmission. Airway management and airway endoscopy, whether awake or sedated, expose operators to infectious aerosols, posing risks to staff. This commentary provides background on the outbreak, highlights critical considerations around mitigating infectious aerosol contact, and outlines best practices for airway-related clinical decision making during the COVID-19 pandemic. What otolaryngologists need to know and what actions are required are considered alongside the implications of increasing demand for tracheostomy. Approaches to managing the airway are presented, emphasizing safety of patients and the health care team.", "qid": 1, "docid": "6mzv33vv", "rank": 99, "score": 4.395999908447266}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 1, "docid": "abj9b0x0", "rank": 100, "score": 4.395998954772949}]}
{"query": "how does the coronavirus respond to changes in the weather", "hits": [{"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare, and respond to COVID-19 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID-19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle-income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time-based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short- and long-term interventions to manage outbreaks at the international, national, and subnational levels in the region.", "qid": 2, "docid": "w5kjmw88", "rank": 1, "score": 10.456899642944336}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID\u201019 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID\u201019 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time\u2010based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short\u2010 and long\u2010term interventions to manage outbreaks at the international, national and sub\u2010national levels in the region. This article is protected by copyright. All rights reserved.", "qid": 2, "docid": "gan10za0", "rank": 2, "score": 10.339400291442871}, {"content": "Title: Climate Change and Human Health Impacts in the United States: An Update on the Results of the U.S. National Assessment Content: The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure\u2013response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.", "qid": 2, "docid": "124czudi", "rank": 3, "score": 9.447699546813965}, {"content": "Title: Weather Conditions and COVID-19 Transmission: Estimates and Projections Content: Background: Understanding and projecting the spread of COVID-19 requires reliable estimates of how weather components are associated with the transmission of the virus. Prior research on this topic has been inconclusive. Identifying key challenges to reliable estimation of weather impact on transmission we study this question using one of the largest assembled databases of COVID-19 infections and weather. Methods: We assemble a dataset that includes virus transmission and weather data across 3,739 locations from December 12, 2019 to April 22, 2020. Using simulation, we identify key challenges to reliable estimation of weather impacts on transmission, design a statistical method to overcome these challenges, and validate it in a blinded simulation study. Using this method and controlling for location-specific response trends we estimate how different weather variables are associated with the reproduction number for COVID-19. We then use the estimates to project the relative weather-related risk of COVID-19 transmission across the world and in large cities. Results: We show that the delay between exposure and detection of infection complicates the estimation of weather impact on COVID-19 transmission, potentially explaining significant variability in results to-date. Correcting for that distributed delay and offering conservative estimates, we find a negative relationship between temperatures above 25 degrees Celsius and estimated reproduction number ([R]), with each degree Celsius associated with a 3.1% (95% CI, 1.5% to 4.8%) reduction in [R]. Higher levels of relative humidity strengthen the negative effect of temperature above 25 degrees. Moreover, one millibar of additional pressure increases [R] by approximately 0.8 percent (95% CI, 0.6% to 1%) at the median pressure (1016 millibars) in our sample. We also find significant positive effects for wind speed, precipitation, and diurnal temperature on [R]. Sensitivity analysis and simulations show that results are robust to multiple assumptions. Despite conservative estimates, weather effects are associated with a 43% change in [R] between the 5th and 95th percentile of weather conditions in our sample. Conclusions: These results provide evidence for the relationship between several weather variables and the spread of COVID-19. However, the (conservatively) estimated relationships are not strong enough to seasonally control the epidemic in most locations.", "qid": 2, "docid": "526elsrf", "rank": 4, "score": 8.486900329589844}, {"content": "Title: Comparison of culturable antibiotic-resistant bacteria in polluted and non-polluted air in Beijing, China Content: Abstract Background Air pollution has been a serious health issue in Beijing for years. Airborne antibiotic-resistant bacteria could be a potential health crisis as reserve of antibiotic resistance transmission in environment. The composition and antibiotic resistance pattern of culturable bacterial community and how these are affected by air pollution remain unclear. Objectives This study aimed to compare the compositions and antibiotic resistance patterns of culturable bacteria in polluted and non-polluted weather conditions in Beijing. Methods Air samples were collected indoors and outdoors during polluted and non-polluted weather using six-stage Andersen Samplers. For each isolated bacterium, the 16S ribosomal RNA gene was amplified, sequenced, and blasted against the National Center for Biotechnology Information database Antibiotic resistance was conducted by antimicrobial susceptibility testing. Results Bacterial concentration in polluted weather was significantly higher than in non-polluted weather, both indoors and outdoors (P < 0.05). Gram-positive bacteria (GPB) were dominant in both weathers but gram-negative bacteria (GNB) were more abundant in polluted weather than non-polluted weather both indoors and outdoors. Multidrug-resistant (MDR) bacteria occupied 23.7% of all bacterial isolates, 22.4% of isolates from polluted weather and 27.8% of isolates from non-polluted weather. Penicillins were resisted by 72.4% and 83.3% of isolates from polluted and non-polluted weather, respectively. Conclusions The bacterial concentration was significantly higher in polluted weather, compared to non-polluted weather. Polluted weather is correlated with changes in the bacterial composition in the air, with a greater abundance of GNB. Penicillins was resisted by over 70% of bacterial isolates. The abundance of MDR bacteria suggested potential risks for human health.", "qid": 2, "docid": "h5ufxzv9", "rank": 5, "score": 8.259900093078613}, {"content": "Title: Does weather affect the growth rate of COVID-19, a study to comprehend transmission dynamics on human health Content: The undefendable outbreak of novel coronavirus (SARS-COV-2) lead to a global health emergency due to its higher transmission rate and longer symptomatic duration, created a health surge in a short time. Since Nov 2019 the outbreak in China, the virus is spreading exponentially everywhere. The current study focuses on the relationship between environmental parameters and the growth rate of COVID-19. The statistical analysis suggests that the temperature changes retarded the growth rate and found that -6.28{degrees}C and +14.51{degrees}C temperature is the favorable range for COVID-19 growth. Gutenberg- Richter's relationship is used to estimate the mean daily rate of exceedance of confirmed cases concerning the change in temperature. Temperature is the most influential parameter that reduces the growth at the rate of 13-16 cases/day with a 1{degrees}C rise in temperature.", "qid": 2, "docid": "r1yjphnn", "rank": 6, "score": 8.025500297546387}, {"content": "Title: Does weather affect the growth rate of COVID-19, a study to comprehend transmission dynamics on human health Content: Abstract The undefendable outbreak of novel coronavirus (SARS-COV-2) lead to a global health emergency due to its higher transmission rate and longer symptomatic duration, created a health surge in a short time. Since Nov 2019 the outbreak in China, the virus is spreading exponentially everywhere. The current study focuses on the relationship between environmental parameters and the growth rate of COVID-19. The statistical analysis suggests that the temperature changes retarded the growth rate and found that -6.28\u00b0C and +14.51\u00b0C temperature is the favorable range for COVID-19 growth. Gutenberg- Richter's relationship is used to estimate the mean daily rate of exceedance of confirmed cases concerning the change in temperature. Indeed, temperature is the most influential parameter that reduces the growth at the rate of 13-17 cases/day with a 1\u00b0C rise in temperature.", "qid": 2, "docid": "w7ycc07b", "rank": 7, "score": 8.02549934387207}, {"content": "Title: Bats and Emerging Infections: An Ecological and Virological Puzzle Content: More than 200 viruses have been detected in bats. Some unique bat characteristics can explain the roles played in the maintenance and transmission of viruses: long phylogenetic history can have originated coevolution processes, great number of species are adapted to live in different environments, big mobility, long lifespan and gregarious behaviour of many species. To analyse zoonoses long longitudinal studies are needed with a multidisciplinary approximation to obtain the following eco-epidemiological data: colony size, number of bats per species, population structure, behaviour of each species, degree of contact between bats, social structure, remaining time of bats in the colony, colony type, foraging area, turnover rate of individuals, shelter temperature, relationship with other colonies and co-infection processes. These data allows assessing the epidemiological risk and which preventive measures are necessary to take. The structure and functionality of ecosystems are changing worldwide at an unprecedented rate and can modify the interactions between humans and infected bats. There are more or less local factors that can affect the emergence and spread of diseases (environmental alterations, changes in land use, human population growth, changes in human socioeconomic behavior or social structure, people mobility increase, trade increase, forest fires, extreme weather events, wars, breakdown in public health infrastructure, etc.). Twenty-three percent of all bat species in the world are decreasing. How does the regression of bat species affect the dynamic of viruses? The dichotomy between health risk and bat preservation is compatible with a preventive task based on more information and training.", "qid": 2, "docid": "amzc5yrd", "rank": 8, "score": 7.9730000495910645}, {"content": "Title: Opening up while locking down: how an Irish independent sector mental health service is responding to the COVID-19 crisis? Content: The COVID-19 pandemic poses a particular set of challenges for health services. Some of these are common across all services (e.g. strategies to minimise infections; timely testing for patients and staff; and sourcing appropriate personal protective equipment (PPE)) and some are specific to mental health services (e.g. how to access general medical services quickly; how to safely deliver a service that traditionally depends on intensive face to face contact; how to isolate someone who does not wish to do so; and how to source sufficient PPE in the face of competing demands for such equipment). This paper describes how St Patrick's Mental Health Services (SPMHS) chose to address this unfolding and ever-changing crisis, how it developed its strategy early based on a clear set of objectives and how it adapted (and continues to adapt) to the constantly evolving COVID-19 landscape.", "qid": 2, "docid": "16k5946u", "rank": 9, "score": 7.859799861907959}, {"content": "Title: Opening up while locking down: how an Irish independent sector mental health service is responding to the COVID-19 crisis Content: The COVID-19 pandemic poses a particular set of challenges for health services. Some of these are common across all services (e.g. strategies to minimise infections; timely testing for patients and staff; and sourcing appropriate personal protective equipment (PPE)) and some are specific to mental health services (e.g. how to access general medical services quickly; how to safely deliver a service that traditionally depends on intensive face to face contact; how to isolate someone who does not wish to do so; and how to source sufficient PPE in the face of competing demands for such equipment). This paper describes how St Patrick\u2019s Mental Health Services (SPMHS) chose to address this unfolding and ever-changing crisis, how it developed its strategy early based on a clear set of objectives and how it adapted (and continues to adapt) to the constantly evolving COVID-19 landscape.", "qid": 2, "docid": "xwz7hj2b", "rank": 10, "score": 7.859798908233643}, {"content": "Title: 'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'. Content: Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.", "qid": 2, "docid": "i7vx1sg5", "rank": 11, "score": 7.848599910736084}, {"content": "Title: Defence in Depth Against Human Extinction: Prevention, Response, Resilience, and Why They All Matter Content: We look at classifying extinction risks in three different ways, which affect how we can intervene to reduce risk. First, how does it start causing damage? Second, how does it reach the scale of a global catastrophe? Third, how does it reach everyone? In all of these three phases there is a defence layer that blocks most risks: First, we can prevent catastrophes from occurring. Second, we can respond to catastrophes before they reach a global scale. Third, humanity is resilient against extinction even in the face of global catastrophes. The largest probability of extinction is posed when all of these defences are weak, that is, by risks we are unlikely to prevent, unlikely to successfully respond to, and unlikely to be resilient against. We find that it\u2019s usually best to invest significantly into strengthening all three defence layers. We also suggest ways to do so tailored to the classes of risk we identify. Lastly, we discuss the importance of underlying risk factors \u2013 events or structural conditions that may weaken the defence layers even without posing a risk of immediate extinction themselves.", "qid": 2, "docid": "4cjlolp6", "rank": 12, "score": 7.703000068664551}, {"content": "Title: Analysis on Novel Coronavirus (COVID-19) Using Machine Learning Methods Content: In this paper, we are working on a pandemic of novel coronavirus (COVID-19). COVID-19 is an infectious disease, it creates severe damage in the lungs. COVID-19 causes illness in humans and has killed many people in the entire world. However, this virus is reported as a pandemic by the World Health Organization (WHO) and all countries are trying to control and lockdown all places. The main objective of this work is to solve the five different tasks such as I) Predicting the spread of coronavirus across regions. II) Analyzing the growth rates and the types of mitigation across countries. III) Predicting how the epidemic will end. IV) Analyzing the transmission rate of the virus. V) Correlating the coronavirus and weather conditions. The advantage of doing these tasks to minimize the virus spread by various mitigation, how well the mitigations are working, how many cases have been prevented by this mitigations, an idea about the number of patients that will recover from the infection with old medication, understand how much time will it take to for this pandemic to end, we will be able to understand and analyze how fast or slow the virus is spreading among regions and the infected patient to reduce the spread based clear understanding of the correlation between the spread and weather conditions. In this paper, we propose a novel Support Vector Regression method to analysis five different tasks related to novel coronavirus. In this work, instead of simple regression line we use the supported vectors also to get better classification accuracy. Our approach is evaluated and compared with other well-known regression models on standard available datasets. The promising results demonstrate its superiority in both efficiency and accuracy.", "qid": 2, "docid": "qp77vl6h", "rank": 13, "score": 7.700300216674805}, {"content": "Title: Does temperature and humidity influence the spread of Covid-19?: A preliminary report Content: INTRODUCTION: Climate change has been known to influence infectious diseases. The reason for this being the fact; disease agents and their vectors each have particular environments that are optimal for growth, survival, transport, and dissemination. MATERIALS AND METHODS: The WHO's website was accessed to look for the Novel Coronavirus (COVID-19) situation dashboard and comprehensively study and assess the report. An attempt was made to look for countries, areas or territories with maximum and minimum number of cases of lab confirmed COVID cases. Further, we entered the words \u201cClimate\u201c in google for each of the aforementioned countries and searched for the results. A comparison was established by including countries from both the hemispheres (northern and southern). The preliminary analysis was based on the reports from countries with established testing facilities for Covid-19. RESULTS: The report suggests that countries with higher number of cases are the countries with cold weather. These are also the countries with low humidity which could be favoring the transmission and survival of the SARS-COV-2. CONCLUSIONS: The results though preliminary point to a pattern which favors the hypothesis that the extensive spread of Covid-19 maybe limited by temperature and humidity.", "qid": 2, "docid": "ws03xsho", "rank": 14, "score": 7.350800037384033}, {"content": "Title: Using Mobility for Electrical Load Forecasting During the COVID-19 Pandemic Content: The novel coronavirus (COVID-19) pandemic has posed unprecedented challenges for the utilities and grid operators around the world. In this work, we focus on the problem of load forecasting. With strict social distancing restrictions, power consumption profiles around the world have shifted both in magnitude and daily patterns. These changes have caused significant difficulties in short-term load forecasting. Typically algorithms use weather, timing information and previous consumption levels as input variables, yet they cannot capture large and sudden changes in socioeconomic behavior during the pandemic. In this paper, we introduce mobility as a measure of economic activities to complement existing building blocks of forecasting algorithms. Mobility data acts as good proxies for the population-level behaviors during the implementation and subsequent easing of social distancing measures. The major challenge with such dataset is that only limited mobility records are associated with the recent pandemic. To overcome this small data problem, we design a transfer learning scheme that enables knowledge transfer between several different geographical regions. This architecture leverages the diversity across these regions and the resulting aggregated model can boost the algorithm performance in each region's day-ahead forecast. Through simulations for regions in the US and Europe, we show our proposed algorithm can outperform conventional forecasting methods by more than three-folds. In addition, we demonstrate how the proposed model can be used to project how electricity consumption would recover based on different mobility scenarios.", "qid": 2, "docid": "9se0wm4t", "rank": 15, "score": 7.324999809265137}, {"content": "Title: Effects of Leachates from UV-Weathered Microplastic in Cell-Based Bioassays. Content: Standard ecotoxicological testing of microplastic does not provide insight into the influence that environmental weathering by, e.g., UV light has on related effects. In this study, we leached chemicals from plastic into artificial sea water during simulated UV-induced weathering. We tested largely additive-free pre-production polyethylene, polyethylene terephthalate, polypropylene and polystyrene and two types of plastic obtained from electronic equipment as positive controls. Leachates were concentrated by solid-phase extraction and dosed into cell-based bioassays that cover i) cytotoxicity; ii) activation of metabolic enzymes via binding to the arylhydrocarbon receptor (AhR) and the peroxisome proliferator-activated receptor (PPAR\u03b3); iii) specific, receptor-mediated effects (estrogenicity, ER\uf061); and iv) adaptive response to oxidative stress (AREc32). LC-HRMS analysis was used to identify possible chain-scission products of polymer degradation, which were then tested in AREc32 and PPAR\u03b3. Explicit activation of all assays by the positive controls provided proof-of-concept of the experimental setup to demonstrate effects of chemicals liberated during weathering. All plastic leachates activated the oxidative stress response, in most cases with increased induction by UV-treated samples compared to dark controls. For PPAR\u03b3, polyethylene-specific effects were partially explained by the detected dicarboxylic acids. Since the pre-production plastic showed low effects often in the range of the blanks future studies should investigate implications of weathering on end consumer products containing additives.", "qid": 2, "docid": "r7fhr7qa", "rank": 16, "score": 7.079100131988525}, {"content": "Title: The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care Content: The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.", "qid": 2, "docid": "0akyr7xz", "rank": 17, "score": 7.067200183868408}, {"content": "Title: The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care Content: Summary The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging \u2018return to normal\u2019 following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.", "qid": 2, "docid": "og3myz22", "rank": 18, "score": 7.067199230194092}, {"content": "Title: Advice-giving in newspaper weather commentaries Content: Abstract Receiving accurate and timely advice about extreme weather events can impact a person's likelihood to survive, cope with and minimise exposure. Advice-giving seems to be a common interpersonal strategy in weather commentaries in many Chinese newspapers, yet research into weather advice-giving is greatly lacking. This study investigated whether the discourse of advice-giving in newspaper weather commentaries differed depending on the newspaper source and/or on the weather reported. We focused on two popular metropolitan newspapers: Beijing Morning Post and Beijing Evening News. Forty texts from each source were chosen (20 for ordinary weather and 20 for extreme weather). Results showed that the advice given stems from a vast reservoir of advice themes, and we found clear differences depending on weather, with significantly more advice given during extreme events. We also found that Beijing Evening News, in general, provided more advice in their weather commentaries. Finally, writers who were prone to take an authoritative stance tended to increase their use of imperatives and \u201chigh-status\u201d vocatives during extreme weather, whereas those who positioned themselves \u201cwith\u201d their readers also used more imperatives, but did not change their vocative preferences.", "qid": 2, "docid": "kftchnhz", "rank": 19, "score": 7.03439998626709}, {"content": "Title: The COVID-19 Crisis: An Opportunity to Integrate Food Democracy into Post-Pandemic Food Systems Content: The world economy is sliding yet into another recession (having arguably barely recovered from the previous economic downturn) due to the worldwide pressures and tensions created by the COVID-19 pandemic.(1) With most countries in the world under lockdown (or in similar situations), almost all food is now consumed in the household. Arguably, agricultural producers and the retail industry appear to be the best placed to weather the storm in order to respond to such a change in demand. However, this is overly simplistic. Recent news of empty shelves in supermarkets whilst dairy farmers have been forced to pour milk down the drain have gone viral.", "qid": 2, "docid": "8eitzlpf", "rank": 20, "score": 7.030700206756592}, {"content": "Title: The COVID-19 pandemic's impact on U.S. electricity demand and supply: an early view from the data Content: After the onset of the recent COVID-19 pandemic, a number of studies reported on possible changes in electricity consumption trends. The overall theme of these reports was that ``electricity use has decreased during the pandemic, but the power grid is still reliable''---mostly due to reduced economic activity. In this paper we analyze electricity data upto end of May 2020, examining both electricity demand and variables that can indicate stress on the power grid, such as peak demand and demand ramp-rate. We limit this study to three states in the USA: New York, California, and Florida. The results indicate that the effect of the pandemic on electricity demand is not a simple reduction from comparable time frames, and there are noticeable differences among regions. The variables that can indicate stress on the grid also conveyed mixed messages: some indicate an increase in stress, some indicate a decrease, and some do not indicate any clear difference. A positive message is that some of the changes that were observed around the time stay-at-home orders were issued appeared to revert back by May 2020. A key challenge in ascribing any observed change to the pandemic is correcting for weather. We provide a weather-correction method, apply it to a small city-wide area, and discuss the implications of the estimated changes in demand. The weather correction exercise underscored that weather-correction is as challenging as it is important.", "qid": 2, "docid": "mja93ena", "rank": 21, "score": 7.005199909210205}, {"content": "Title: The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach Content: The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states.", "qid": 2, "docid": "ysa8vb9x", "rank": 22, "score": 6.929500102996826}, {"content": "Title: A systematic review of peer-reviewed literature authored by medical professionals regarding US biomedicine's role in responding to climate change. Content: Extant literature illustrates a substantive impact on human health because of climate change. Despite this, discussions of the ethical and policymaking role of US health care's response to this problem are underdeveloped within peer-reviewed literature indexed in core medical databases. We conducted a systematic literature review in August 2017 at Vanderbilt University Medical Center of the following medical, business and policy databases to examine the state of inquiry on this topic: PubMed, CINAHL, PsychINFO, JAMA Network, Health Affairs, Business Source Complete, Greylit.org, LexisNexis Academic, Proquest Dissertations and Theses Global. An initial sample of n = 4434 rendered n = 75 articles precisely addressing this question following a two-tiered systematic examination of content. US medical professionals were most concerned by the health impacts of air pollution and respiratory complications, extreme weather events, and rising infectious/vector-borne diseases. They were least concerned by rising rates of migration and stresses to sanitation systems. Medical professionals took a broadly proactive stance to the issue, highlighting the need to implement education and advocacy strategies. Politics was the least pertinent motivation for climate change-related recommendations. Furthermore, partnerships between health care and public agencies were identified as holding the greatest potential for meaningful change. Mitigation approaches were slightly more common than adaptation approaches. We conclude that, while the enthusiasm of the medical community is commendable, efforts to address climate change in US health care are overly fractured, and lack the necessary expertise for efficaciousness.", "qid": 2, "docid": "rkkimpbx", "rank": 23, "score": 6.824100017547607}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January\u2013February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5\u20137 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from \u221228.0\u00b0C to 30.1\u00b0C, minimum daily temperature from \u221242.4\u00b0C to 23.0\u00b0C, maximum solar radiation from 0.04 to 2.74 MJm(\u22122) and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "be7gxvl7", "rank": 24, "score": 6.7621002197265625}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance elsewhere. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 cases. Weekly means of maximum daily temperature varied from -28.0 to 30.1 \u00b0C, minimum daily temperature from -42.4 to 23.0 \u00b0C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "r141na6j", "rank": 25, "score": 6.762099266052246}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops.Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation.Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios.Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from -28.0\u00b0C to 30.1\u00b0C, minimum daily temperature from -42.4\u00b0C to 23.0\u00b0C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence.Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "upw6fulv", "rank": 26, "score": 6.76209831237793}, {"content": "Title: Extreme water-related weather events and waterborne disease Content: Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought. We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events. Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55\u00b72% and 52\u00b79% of accounts, respectively. The most common pathogens reported in these outbreaks were Vibrio spp. (21\u00b76%) and Leptospira spp. (12\u00b77%). Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53\u00b77%). Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities.", "qid": 2, "docid": "exqza1kg", "rank": 27, "score": 6.747399806976318}, {"content": "Title: Mental health and capacity laws in Northern Ireland and the COVID-19 pandemic: Examining powers, procedures and protections under emergency legislation Content: This article examines the changes made to mental health and capacity laws in Northern Ireland through temporary emergency legislation, known as the Coronavirus Act 2020. The purpose of the legislation was to respond to the emergency situation created by the COVID-19 pandemic, in particular the increase pressure placed on health services in the United Kingdom. An overview is provided of the government's rationale for the changes to Northern Ireland mental health and capacity laws, as well as exploring how they are likely to be operationalised in practice. Consideration is also given as to how such changes may impact upon existing human rights protections for persons assessed as lacking mental capacity. It is argued that it is important that regular parliamentary oversight is maintained in relation to the potential impact and consequences of such changes during the period they are in force. This should be done in order to assess whether they remain a necessary, proportionate and least restrictive response to the challenges faced in managing mental health and capacity issues in Northern Ireland during this public health emergency.", "qid": 2, "docid": "ma27v97d", "rank": 28, "score": 6.74560022354126}, {"content": "Title: Traumatic Times Content: Discusses how businesses are impacted by traumatic events and pandemics such as the current Coronavirus (COVID-19) As I write this in late March, we are early in the coronavirus (COVID-19) pandemic It is like nothing any of us have experienced before, except perhaps the very few who may have lived through the flu pandemic of 1918-1920 The COVID-19 crisis is like a combination of all the worst we've seen There is social trauma as we isolate ourselves, lose some individual liberties, and try to work from home We don't know when society will return to normal and, when it does, how it will have changed", "qid": 2, "docid": "uczrmgq3", "rank": 29, "score": 6.700200080871582}, {"content": "Title: One Size Does Not Fit All: How to Rapidly Deploy Intubation Practice Changes in a Pediatric Hospital During the Coronavirus Disease 2019 Pandemic Content:", "qid": 2, "docid": "y08iot2a", "rank": 30, "score": 6.659299850463867}, {"content": "Title: Epilepsy self-management during a pandemic: Experiences of people with epilepsy Content: The purpose of this descriptive study was to, from the perspective of adult people with epilepsy (PWE) and caregivers of PWE, explore the effects of the current pandemic and resulting societal changes on epilepsy self-management. Ninety-four respondents completed a mixed-methods quantitative and qualitative survey focused on their epilepsy self-management experiences during the coronavirus disease-19 (COVID-19) pandemic. Respondents noted significant disruption in epilepsy self-management. Lack of ability to obtain medications or see epilepsy providers, as well as increased stress, social isolation, and changes in routine were all reported as troublesome, and more than one-third of the sample reported an increase in seizure frequency since the onset of the pandemic. Suggestions are given regarding how to support PWE during future COVID-19 outbreaks and to better prepare PWE and their caregivers for any life-altering events, such as a pandemic, with robust self-management skills that will allow them to maintain the highest level of function possible.", "qid": 2, "docid": "ix2jt350", "rank": 31, "score": 6.656899929046631}, {"content": "Title: The Challenge of Teaching Mission in an Increasingly Mobile and Complex World Content: In a time when old groupings are breaking up, when people are on the move or fleeing conflict and settling elsewhere, when many people are multilingual and are competent in several cultural settings, doing mission has become an ever greater challenge than simple cross-cultural communication. How does one engage in mission on the run? How does one conduct missiological research in ephemeral community that is here today and gone tomorrow? How does one train new missionaries for work in a field that will certainly morph into something else before they get there? Changing times call for new perspectives on mission.", "qid": 2, "docid": "m3dt5kuy", "rank": 32, "score": 6.630799770355225}, {"content": "Title: Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic Content: Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios based on known coronavirus biology. We find that while variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen the climate drives only modest changes to pandemic size. A preliminary analysis of non-pharmaceutical control measures indicates that they may moderate the pandemic-climate interaction via susceptible depletion. Our findings suggest, without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.", "qid": 2, "docid": "aiwxlxzt", "rank": 33, "score": 6.539000034332275}, {"content": "Title: Containing the Anxieties of Children, Parents and Families from a Distance During the Coronavirus Pandemic Content: The coronavirus pandemic and the move to teletherapy has created uncertainty among both clinicians and patients. As therapists who work with children, we have heard from parents who are desperate for support and advice about how to respond to their children\u2019s behavioral changes, as well as those who feel too overwhelmed to continue their children\u2019s sessions at the moment and want to take a break from treatment. We have had to rethink the frame in concrete ways, reimagine how to play, and renegotiate parameters around confidentiality. At a time when fear and uncertainty make mentalizing difficult, the hallmarks of a mentalizing approach\u2014curiosity and flexibility\u2014are most critical. This paper will describe how the Mentalization-Based Treatment for Children (MBT-C) model offers a framework for an integrative approach that can inform treatment via teletherapy, so that clinicians can continue supporting young people and their families through this period. We will begin by describing how the mentalizing stance, particularly an awareness of our own mentalizing capacities in the moment, has become more important than ever. Ways in which clinicians maintain their mentalizing in the face of the mentalizing breakdowns will be also discussed. Finally, we illustrate with clinical vignettes how the developmental levels of mentalizing\u2014attention control, emotion regulation, and explicit mentalizing\u2014can inform the structure, techniques and interventions in teletherapy with children and parents.", "qid": 2, "docid": "v78hscpz", "rank": 34, "score": 6.514400005340576}, {"content": "Title: Effects of school closure on incidence of pandemic influenza in Alberta, Canada. Content: BACKGROUND Control of pandemic influenza by social-distancing measures, such as school closures, is a controversial aspect of pandemic planning. However, investigations of the extent to which these measures actually affect the progression of a pandemic have been limited. OBJECTIVE To examine correlations between the incidence of pandemic H1N1 (pH1N1) influenza in Alberta, Canada, in 2009 and school closures or weather changes, and to estimate the effects of school closures and weather changes on pH1N1 transmission. DESIGN Mathematical transmission models were fit to data that compared the pattern of confirmed pH1N1 cases with the school calendar and weather patterns. SETTING Alberta, Canada, from 19 April 2009 to 2 January 2010. DATA SOURCES 2009 virologic test results, 2006 census data, 2009 daily temperature and humidity data, and 2009 school calendars. MEASUREMENTS Age-specific daily counts of positive results for pH1N1 from the complete database of 35 510 specimens submitted to the Alberta Provincial Laboratory for Public Health for virologic testing from 19 April 2009 to 2 January 2010. RESULTS The ending and restarting of school terms had a major effect in attenuating the first wave and starting the second wave of pandemic influenza cases. Mathematical models suggested that school closure reduced transmission among school-age children by more than 50% and that this was a key factor in interrupting transmission. The models also indicated that seasonal changes in weather had a significant effect on the temporal pattern of the epidemic. LIMITATIONS Data probably represent a small sample of all viral infections. The mathematical models make simplifying assumptions in order to make simulations and analysis feasible. CONCLUSION Analysis of data from unrestricted virologic testing during an influenza pandemic provides compelling evidence that closing schools can have dramatic effects on transmission of pandemic influenza. School closure seems to be an effective strategy for slowing the spread of pandemic influenza in countries with social contact networks similar to those in Canada. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Public Health Agency of Canada.", "qid": 2, "docid": "hra8otj5", "rank": 35, "score": 6.489999771118164}, {"content": "Title: R\u00e4umliche Ausbreitung von COVID-19 durch interregionale Verflechtungen Content: The coronavirus has plunged the global economy into crisis. Since the beginning of March, contact and exit restrictions and bans on business activities have been imposed in Germany, schools have been closed, child care has been suspended, and strict hygiene regulations have been issued. In the meantime, the number of reported new infections has been significantly reduced and the German healthcare system does not appear to be overburdened to date. This is one of the reasons why there is now an intensive debate about easing the regulations, which would allow additional economic activity. The article also examines commuter links and the role they have played in the spread of COVID-19 in Germany as well as bad weather conditions and a high population density.", "qid": 2, "docid": "e4crbz0c", "rank": 36, "score": 6.483500003814697}, {"content": "Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.", "qid": 2, "docid": "svo94kuo", "rank": 37, "score": 6.479300022125244}, {"content": "Title: A case-crossover analysis of the impact of weather on primary cases of Middle East respiratory syndrome Content: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels in the Arabian Peninsula, and zoonotic transmission to people is a sporadic event. In the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. This study aimed to identify meteorological factors that may increase the risk of primary MERS infections in humans. METHODS: A case-crossover design was used to identify associations between primary MERS cases and preceding weather conditions within the 2-week incubation period in Saudi Arabia using univariable conditional logistic regression. Cases with symptom onset between January 2015 \u2013 December 2017 were obtained from a publicly available line list of human MERS cases maintained by the World Health Organization. The complete case dataset (N = 1191) was reduced to approximate the cases most likely to represent spillover transmission from camels (N = 446). Data from meteorological stations closest to the largest city in each province were used to calculate the daily mean, minimum, and maximum temperature ((\u03bf)C), relative humidity (%), wind speed (m/s), and visibility (m). Weather variables were categorized according to strata; temperature and humidity into tertiles, and visibility and wind speed into halves. RESULTS: Lowest temperature (Odds Ratio = 1.27; 95% Confidence Interval = 1.04\u20131.56) and humidity (OR = 1.35; 95% CI = 1.10\u20131.65) were associated with increased cases 8\u201310 days later. High visibility was associated with an increased number of cases 7 days later (OR = 1.26; 95% CI = 1.01\u20131.57), while wind speed also showed statistically significant associations with cases 5\u20136 days later. CONCLUSIONS: Results suggest that primary MERS human cases in Saudi Arabia are more likely to occur when conditions are relatively cold and dry. This is similar to seasonal patterns that have been described for other respiratory diseases in temperate climates. It was hypothesized that low visibility would be positively associated with primary cases of MERS, however the opposite relationship was seen. This may reflect behavioural changes in different weather conditions. This analysis provides key initial evidence of an environmental component contributing to the development of primary MERS-CoV infections.", "qid": 2, "docid": "jc1k3fki", "rank": 38, "score": 6.470600128173828}, {"content": "Title: Coronavirus (COVID-19) in the United Kingdom: A personality-based perspective on concerns and intention to self-isolate Content: Objectives Public behaviour change is necessary to contain the spread of coronavirus (COVID-19). Based on the reinforcement sensitivity theory (RST) framework, this study presents an examination of individual differences in some relevant psychological factors. Design Cross-sectional psychometric. Methods UK respondents (N = 202) completed a personality questionnaire (RST-PQ), measures of illness attitudes, concerns about the impact of coronavirus on health services and socio-economic infrastructures, personal safety, and likelihood of voluntary self-isolation. Results Respondents most concerned were older, had negative illness attitudes, and scored higher on reward reactivity (RR), indicating the motivation to take positive approach action despite prevailing worry/anxiety. Personal safety concerns were highest in those with negative illness attitudes and higher fight-flight-freeze system (FFFS, reflecting fear/avoidance) scores. Results suggest people are experiencing psychological conflict: between the urge to stay safe (FFFF-related) and the desire to maintain a normal, pleasurable (RR-related) life. Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward-related displacement activity. Intended self-isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self-isolate. Conclusions Interventions need to consider individual differences in psychological factors in behaviour change, and we discuss relevant literature to inform policy makers and communicators. Statement of contribution What is already known on this subject? Reinforcement sensitivity theory (RST) personality systems can influence perception of persuasive health messages. However, there is limited evidence for their direct effects on health concerns and behaviours, and none relating to specific infectious diseases. What does this study add? Reward reactivity (RR) is associated with concern about impact of coronavirus on the NHS and other social infrastructures, indicating the motivation to take positive-approach action despite worry/anxiety. Personal safety concerns are related to fight-flight-freeze system traits (FFFS, reflecting fear/avoidance). Intended self-isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self-isolate. Results suggest psychological conflict: between the urge to stay safe (FFFF-related) and the desire to maintain a normal, pleasurable life (RR-related). Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward-related displacement activity.", "qid": 2, "docid": "1d1xhk99", "rank": 39, "score": 6.449699878692627}, {"content": "Title: Coronavirus (COVID\u201019) in the United Kingdom: A personality\u2010based perspective on concerns and intention to self\u2010isolate Content: OBJECTIVES: Public behaviour change is necessary to contain the spread of coronavirus (COVID\u201019). Based on the reinforcement sensitivity theory (RST) framework, this study presents an examination of individual differences in some relevant psychological factors. DESIGN: Cross\u2010sectional psychometric. METHODS: UK respondents (N = 202) completed a personality questionnaire (RST\u2010PQ), measures of illness attitudes, concerns about the impact of coronavirus on health services and socio\u2010economic infrastructures, personal safety, and likelihood of voluntary self\u2010isolation. RESULTS: Respondents most concerned were older, had negative illness attitudes, and scored higher on reward reactivity (RR), indicating the motivation to take positive approach action despite prevailing worry/anxiety. Personal safety concerns were highest in those with negative illness attitudes and higher fight\u2013flight\u2013freeze system (FFFS, reflecting fear/avoidance) scores. Results suggest people are experiencing psychological conflict: between the urge to stay safe (FFFF\u2010related) and the desire to maintain a normal, pleasurable (RR\u2010related) life. Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward\u2010related displacement activity. Intended self\u2010isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self\u2010isolate. CONCLUSIONS: Interventions need to consider individual differences in psychological factors in behaviour change, and we discuss relevant literature to inform policy makers and communicators. STATEMENT OF CONTRIBUTION: What is already known on this subject? Reinforcement sensitivity theory (RST) personality systems can influence perception of persuasive health messages. However, there is limited evidence for their direct effects on health concerns and behaviours, and none relating to specific infectious diseases. What does this study add? Reward reactivity (RR) is associated with concern about impact of coronavirus on the NHS and other social infrastructures, indicating the motivation to take positive\u2010approach action despite worry/anxiety. Personal safety concerns are related to fight\u2013flight\u2013freeze system traits (FFFS, reflecting fear/avoidance). Intended self\u2010isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self\u2010isolate. Results suggest psychological conflict: between the urge to stay safe (FFFF\u2010related) and the desire to maintain a normal, pleasurable life (RR\u2010related). Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward\u2010related displacement activity;", "qid": 2, "docid": "79rpu3qf", "rank": 40, "score": 6.4496989250183105}, {"content": "Title: Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks Content: Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.", "qid": 2, "docid": "uxq43me8", "rank": 41, "score": 6.44950008392334}, {"content": "Title: Communication practices for delivering health behaviour change conversations in primary care: a systematic review and thematic synthesis. Content: BACKGROUND Clinical guidelines exhort clinicians to encourage patients to improve their health behaviours. However, most offer little support on how to have these conversations in practice. Clinicians fear that health behaviour change talk will create interactional difficulties and discomfort for both clinician and patient. This review aims to identify how healthcare professionals can best communicate with patients about health behaviour change (HBC). METHODS We included studies which used conversation analysis or discourse analysis to study recorded interactions between healthcare professionals and patients. We followed an aggregative thematic synthesis approach. This involved line-by-line coding of the results and discussion sections of included studies, and the inductive development and hierarchical grouping of descriptive themes. Top-level themes were organised to reflect their conversational positioning. RESULTS Of the 17,562 studies identified through systematic searching, ten papers were included. Analysis resulted in 10 top-level descriptive themes grouped into three domains: initiating; carrying out; and closing health behaviour change talk. Of three methods of initiation, two facilitated further discussion, and one was associated with outright resistance. Of two methods of conducting behaviour change talk, one was associated with only minimal patient responses. One way of closing was identified, and patients did not seem to respond to this positively. Results demonstrated a series of specific conversational practices which clinicians use when talking about HBC, and how patients respond to these. Our results largely complemented clinical guidelines, providing further detail on how they can best be delivered in practice. However, one recommended practice - linking a patient's health concerns and their health behaviours - was shown to receive variable responses and to often generate resistance displays. CONCLUSIONS Health behaviour change talk is smoothly initiated, conducted, and terminated by clinicians and this rarely causes interactional difficulty. However, initiating conversations by linking a person's current health concern with their health behaviour can lead to resistance to advice, while other strategies such as capitalising on patient initiated discussions, or collaborating through question-answer sequences, may be well received.", "qid": 2, "docid": "tuykwhtp", "rank": 42, "score": 6.430099964141846}, {"content": "Title: The Weather Impacts the Outbreak of COVID-19 in Mainland China Content: Recent literature has suggested that climate conditions have considerably significant influences on the transmission of coronavirus COVID-19. However, there is a lack of comprehensive study that investigates the relationships between multiple weather factors and the development of COVID-19 pandemic while excluding the impact of social factors. In this paper, we study the relationships between six main weather factors and the infection statistics of COVID-19 on 250 cities in Mainland China. Our correlation analysis using weather and infection statistics indicates that all the studied weather factors are correlated with the spread of COVID-19, where precipitation shows the strongest correlation. We also build a weather-aware predictive model that forecasts the number of infected cases should there be a second wave of the outbreak in Mainland China. Our predicted results show that cities located in different geographical areas are likely to be challenged with the second wave of COVID-19 at very different time periods and the severity of the outbreak varies to a large degree, in correspondence with the varying weather conditions.", "qid": 2, "docid": "akb96git", "rank": 43, "score": 6.427999973297119}, {"content": "Title: A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.", "qid": 2, "docid": "09nr9dho", "rank": 44, "score": 6.385900020599365}, {"content": "Title: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey Content: The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent's country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.", "qid": 2, "docid": "b54dymlu", "rank": 45, "score": 6.374100208282471}, {"content": "Title: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey Content: Abstract The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent\u2019s country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.", "qid": 2, "docid": "s5u57av2", "rank": 46, "score": 6.374099254608154}, {"content": "Title: Association of COVID-19 pandemic with meteorological parameters over Singapore Content: Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "qid": 2, "docid": "pwul6lco", "rank": 47, "score": 6.354400157928467}, {"content": "Title: Disaster resiliency of U.S. local governments: Insights to strengthen local response and recovery from the COVID\u201019 pandemic Content: This research presents implications of the global pandemic on local government resiliency in the United States. We explore insights from local government officials and managers at the frontlines of response and recovery efforts to the biological natural disaster. Also, findings from the latest nationwide survey of U.S. local governments regarding their preparedness for weather\u2010related natural disasters informs responses to the current crisis. Results indicate that local governments are innovating and taking strategic actions to fight the virus. This, even though COVID\u201019 has exposed social inequities exacerbated as the virus spreads. Survey findings of disaster readiness of local governments to weather\u2010related disasters shows that small, resource poor governments will not be able to respond well, and social inequities will grow. Policy strategies at all levels of government must recognize and account for these inequities as threat of this virus subsides, to support stronger, more effective readiness for the next biological catastrophe. This article is protected by copyright. All rights reserved.", "qid": 2, "docid": "tdsyengw", "rank": 48, "score": 6.3368000984191895}, {"content": "Title: Pandemics, regional outbreaks, and sudden-onset disasters Content: Pandemics of influenza, cholera, and plague are part of global history. Regional epidemics and pandemics of infectious diseases, primarily influenza A, continue to cause significant morbidity and mortality while remaining unpredictable in nature. Sudden-onset disasters such as earthquakes and floods occur with little warning. The consequences of climate change and environmental degradation can only be expected to increase the incidence of some infectious diseases and weather-related crises, adding to the unpredictability of such events. Health system leaders, both in public health and healthcare, need to understand the international context and how coordination and response across or within jurisdictions will improve the likelihood of successful management of challenges. Public health emergencies respect no borders or political structures. The ability of institutions to adapt quickly can make a difference in health outcomes and a community\u2019s trust in those institutions.", "qid": 2, "docid": "br661awf", "rank": 49, "score": 6.330599784851074}, {"content": "Title: Pandemics, regional outbreaks, and sudden-onset disasters Content: Pandemics of influenza, cholera, and plague are part of global history. Regional epidemics and pandemics of infectious diseases, primarily influenza A, continue to cause significant morbidity and mortality while remaining unpredictable in nature. Sudden-onset disasters such as earthquakes and floods occur with little warning. The consequences of climate change and environmental degradation can only be expected to increase the incidence of some infectious diseases and weather-related crises, adding to the unpredictability of such events. Health leaders, both in public health and healthcare, need to understand the international context and how coordination and response across or within jurisdictions will improve the likelihood of successful management of challenges. Public health emergencies respect no borders or political structures. The ability of institutions to adapt quickly can make a difference in health outcomes and a community's trust in those institutions.", "qid": 2, "docid": "f9pk211l", "rank": 50, "score": 6.330598831176758}, {"content": "Title: Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes Content: We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.", "qid": 2, "docid": "rwh56zhg", "rank": 51, "score": 6.330399990081787}, {"content": "Title: Pathogen seasonality and links with weather in England and Wales: a big data time series analysis Content: BACKGROUND: Many infectious diseases of public health importance display annual seasonal patterns in their incidence. We aimed to systematically document the seasonality of several human infectious disease pathogens in England and Wales, highlighting those organisms that appear weather-sensitive and therefore may be influenced by climate change in the future. METHODS: Data on infections in England and Wales from 1989 to 2014 were extracted from the Public Health England (PHE) SGSS surveillance database. We conducted a weekly, monthly and quarterly time series analysis of 277 pathogen serotypes. Each organism\u2019s time series was forecasted using the TBATS package in R, with seasonality detected using model fit statistics. Meteorological data hosted on the MEDMI Platform were extracted at a monthly resolution for 2001\u20132011. The organisms were then clustered by K-means into two groups based on cross correlation coefficients with the weather variables. RESULTS: Examination of 12.9 million infection episodes found seasonal components in 91/277 (33%) organism serotypes. Salmonella showed seasonal and non-seasonal serotypes. These results were visualised in an online Rshiny application. Seasonal organisms were then clustered into two groups based on their correlations with weather. Group 1 had positive correlations with temperature (max, mean and min), sunshine and vapour pressure and inverse correlations with mean wind speed, relative humidity, ground frost and air frost. Group 2 had the opposite but also slight positive correlations with rainfall (mm, > 1 mm, > 10 mm). CONCLUSIONS: The detection of seasonality in pathogen time series data and the identification of relevant weather predictors can improve forecasting and public health planning. Big data analytics and online visualisation allow the relationship between pathogen incidence and weather patterns to be clarified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5931-6) contains supplementary material, which is available to authorized users.", "qid": 2, "docid": "0x4zrfw3", "rank": 52, "score": 6.328100204467773}, {"content": "Title: A Heuristic Indication and Warning Staging Model for Detection and Assessment of Biological Events Content: OBJECTIVE: This paper presents a model designed to enable rapid detection and assessment of biological threats that may require swift intervention by the international public health community. DESIGN: We utilized Strauss\u2019 grounded theory to develop an expanded model of social disruption due to biological events based on retrospective and prospective case studies. We then applied this model to the temporal domain and propose a heuristic staging model, the Wilson\u2013Collmann Scale for assessing biological event evolution. MEASUREMENTS: We retrospectively and manually examined hard copy archival local media reports in the native vernacular for three biological events associated with substantial social disruption. The model was then tested prospectively through media harvesting based on keywords corresponding to the model parameters. RESULTS: Our heuristic staging model provides valuable information about the features of a biological event that can be used to determine the level of concern warranted, such as whether the pathogen in question is responding to established public health disease control measures, including the use of antimicrobials or vaccines; whether the public health and medical infrastructure of the country involved is adequate to mount the necessary response; whether the country\u2019s officials are providing an appropriate level of information to international public health authorities; and whether the event poses a international threat. The approach is applicable for monitoring open-source (public-domain) media for indications and warnings of such events, and specifically for markers of the social disruption that commonly occur as these events unfold. These indications and warnings can then be used as the basis for staging the biological threat in the same manner that the United States National Weather Service currently uses storm warning models (such as the Saffir-Simpson Hurricane Scale) to detect and assess threatening weather conditions. CONCLUSION: Used as a complement to current epidemiological surveillance methods, our approach could aid global public health officials and national political leaders in responding to biological threats of international public health significance.", "qid": 2, "docid": "4pztbu51", "rank": 53, "score": 6.327899932861328}, {"content": "Title: Changes in Police Calls for Service During the Early Months of the 2020 Coronavirus Pandemic Content: The coronavirus pandemic poses multiple challenges for policing, including the need to continue responding to calls from the public. Several contingency plans warned police to expect a large and potentially overwhelming increase in demand from the public during a pandemic, but (to the author\u2019s knowledge) there is no empirical work on police demand during a major public health emergency. This study used calls-for-service data from 10 large cities in the USA to analyse how calls for service changed during the early months of the 2020 COVID-19 outbreak, compared to forecasts of call volume based on data from previous years. Contrary to previous warnings, overall the number of calls went down during the early weeks of the pandemic. There were substantial reductions in specific call types, such as traffic collisions, and significant increases in others, such as calls to dead bodies. Other types of calls, particularly those relating to crime and order maintenance, continued largely as before. Changes in the frequency of different call types present challenges to law enforcement agencies, particularly since many will themselves be suffering from reduced staffing due to the pandemic. Understanding changes to calls in detail will allow police leaders to put in place evidence-based plans to ensure they can continue to serve the public.", "qid": 2, "docid": "rle6tpx0", "rank": 54, "score": 6.3084001541137695}, {"content": "Title: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Content: Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.", "qid": 2, "docid": "gh58t6eh", "rank": 55, "score": 6.304900169372559}, {"content": "Title: Impact of Daily Weather on COVID-19 outbreak in India Content: The COVID-19 pandemic has outspread obstreperously in India. As of June 04, 2020, more than 2 lakh cases have been confirmed with a death rate of 2.81%. It has been noticed that, out of each 1000 tests, 53 result positively infected. In order to investigate the impact of weather conditions on daily transmission occurring in India, daily data of Maximum (TMax), Minimum (TMin), Mean (TMean) and Dew Point Temperature (TDew), Diurnal Temperature range (TRange), Average Relative Humidity, Range in Relative Humidity, and Wind Speed (WS) over 9 most affected cities are analysed in several time frames: weather of that day, 7, 10, 12, 14, 16 days before transmission. Spearman rank correlation (r) shows significant but low correlation with most of the weather parameters, however, comparatively better association exists on 14 days lag. Diurnal range in Temperature and Relative Humidity shows non-significant correlation. Analysis shows, COVID-19 cases likely to be increased with increasing air temperature, however role of humidity is not clear. Among weather parameters, Minimum Temperature was relatively better correlate than other. 80% of the total confirmed cases were registered when TMax, TMean, TMin, TRange, TDew, and WS on 12-16 days ago vary within a range of 33.6-41.3 deg C, 29.8-36.5 deg C, 24.8-30.4 deg C, 7.5-15.2 deg C, 18.7-23.6 deg C, and 4.2-5.75 m/s respectively, hence, it gives an idea of susceptible weather conditions for such transmission in India. Using Support Vector Machine based regression, the daily cases are profoundly estimated with more than 80% accuracy, which indicate that coronavirus transmission cannot be well linearly correlated with any single weather parameters, rather multivariate non-linear approach must be employed. Accounting lag of 12-16 days, the association found to be excellent, thus depict that there is an incubation period of 12-16 days for coronavirus transmission in Indian scenario.", "qid": 2, "docid": "uj8a09t3", "rank": 56, "score": 6.303699970245361}, {"content": "Title: Association of COVID-19 pandemic with meteorological parameters over Singapore Content: Abstract Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "qid": 2, "docid": "1bxt21za", "rank": 57, "score": 6.295199871063232}, {"content": "Title: Resilience resistance: The challenges and implications of urban resilience implementation Content: Growing concern about major threats, including climate change, environmental disasters, and other hazards, is matched with the increased interest and appeal of the concept of urban resilience. Much scholarly attention has focused on how to define urban resilience, in addition to raising questions about its applicability and usefulness. But those debates typically overlook questions of implementation. Implementation is important not only for how cities respond to threats but also because it can influence how urban resilience is perceived, discussed, and understood. The policy literature suggests that implementation is rarely straightforward and has ideological and normative perspectives embedded within it. Building on this literature, this paper argues that urban resilience implementation raises its own conceptual questions for both theory and practice. Further, implementing urban resilience entails its own unique challenges, such as extensive coordination, maintaining adaptability, divergent time horizons, and diverse outcomes. The paper also introduces the idea of resilience resistance as a new challenge for urban resilience. Resistance refers to the condition in which governance systems inherently develop barriers to change, flexibility, and adaptability through implementation. Several aspects of resistance are highlighted, including fatigue, complacency, and overconfidence. However, the implementation process can also have unintended positive effects on a city's capacity to prepare for and respond to shocks.", "qid": 2, "docid": "noa41knv", "rank": 58, "score": 6.250500202178955}, {"content": "Title: Short Term Effects of Weather on Hand, Foot and Mouth Disease Content: BACKGROUND: Hand, foot, and mouth disease (HFMD) outbreaks leading to clinical and fatal complications have increased since late 1990s; especially in the Asia Pacific Region. Outbreaks of HFMD peaks in the warmer season of the year, but the underlying factors for this annual pattern and the reasons to the recent upsurge trend have not yet been established. This study analyzed the effect of short-term changes in weather on the incidence of HFMD in Singapore. METHODS: The relative risks between weekly HFMD cases and temperature and rainfall were estimated for the period 2001\u20132008 using time series Poisson regression models allowing for over-dispersion. Smoothing was used to allow non-linear relationship between weather and weekly HFMD cases, and to adjust for seasonality and long-term time trend. Additionally, autocorrelation was controlled and weather was allowed to have a lagged effect on HFMD incidence up to 2 weeks. RESULTS: Weekly temperature and rainfall showed statistically significant association with HFMD incidence at time lag of 1\u20132 weeks. Every 1\u00b0C increases in maximum temperature above 32\u00b0C elevated the risk of HFMD incidence by 36% (95% CI = 1.341\u20131.389). Simultaneously, one mm increase of weekly cumulative rainfall below 75 mm increased the risk of HFMD by 0.3% (CI = 1.002\u20131.003). While above 75 mm the effect was opposite and each mm increases of rainfall decreased the incidence by 0.5% (CI = 0.995\u20130.996). We also found that a difference between minimum and maximum temperature greater than 7\u00b0C elevated the risk of HFMD by 41% (CI = 1.388\u20131.439). CONCLUSION: Our findings suggest a strong association between HFMD and weather. However, the exact reason for the association is yet to be studied. Information on maximum temperature above 32\u00b0C and moderate rainfall precede HFMD incidence could help to control and curb the up-surging trend of HFMD.", "qid": 2, "docid": "39yvniki", "rank": 59, "score": 6.218699932098389}, {"content": "Title: Rethinking Global Health Governance in a Changing World Order for Achieving Sustainable Development: The Role and Potential of the \u2018Rising Powers\u2019 Content: The idea of this paper is inspired by the dismal experience and lessons from the initially ineffective global (WHO-led) response to the 2014\u20132016 West African Ebola virus epidemic. It charts the evolution of global health policy and governance in the post-World War II international order to the current post-2015 UN Sustainable Development Goals era. In order to respond adequately existing and emerging health and development challenges across developing regions, the paper argues that global health governance and related structures and institutions must adapt to changing socio-economic circumstances at all levels of decision-making. Against the background of a changing world order characterised by the decline of US-led Western international liberalism and the rise of the emerging nations in the developing world, it identifies the \u2018Rising Powers\u2019 (RPs) among the emerging economies and their soft power diplomacy and international development cooperation strategy as important tools for responding to post-2015 global health challenges. Based on analysis of illustrative examples from the \u2018BRICS\u2019, a group of large emerging economies\u2014Brazil, Russia, India, China and South Africa\u2014the paper develops suggestions and recommendations for the RPs with respect to: (1) stimulating innovation in global health governance and (2) strengthening health systems and health security at country and regional levels. Observing that current deliberations on global health focus largely, but rather narrowly, on what resource inputs are needed to achieve the SDG health targets, this paper goes further and highlights the importance of the \u2018how\u2019 in terms of a leadership and driving role for the RPs: How can the RPs champion global governance reform and innovation aimed at producing strong, resilient and equitable global systems? How can the RPs use soft power diplomacy to enhance disease surveillance and detection capacities and to promote improved regional and international coordination in response to health threats? How can they provide incentives for investment in R&D and manufacturing of medicines to tackle neglected and poverty-related diseases in developing countries?", "qid": 2, "docid": "op5wcxlg", "rank": 60, "score": 6.203100204467773}, {"content": "Title: Weather-inspired ensemble-based probabilistic prediction of COVID-19 Content: The objective of this work is to predict the spread of COVID-19 starting from observed data, using a forecast method inspired by probabilistic weather prediction systems operational today. Results show that this method works well for China: on day 25 we could have predicted well the outcome for the next 35 days. The same method has been applied to Italy and South Korea, and forecasts for the forthcoming weeks are included in this work. For Italy, forecasts based on data collected up to today (24 March) indicate that number of observed cases could grow from the current value of 69,176, to between 101k-180k, with a 50% probability of being between 110k-135k. For South Korea, it suggests that the number of observed cases could grow from the current value of 9,018 (as of the 23rd of March), to values between 8,500 and 9,300, with a 50% probability of being between 8,700 and 8,900. We conclude by suggesting that probabilistic disease prediction systems are possible and could be developed following key ideas and methods from weather forecasting. Having access to skilful daily updated forecasts could help taking better informed decisions on how to manage the spread of diseases such as COVID-19.", "qid": 2, "docid": "3sencqst", "rank": 61, "score": 6.198800086975098}, {"content": "Title: A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00701-020-04482-8) contains supplementary material, which is available to authorized users.", "qid": 2, "docid": "mp2f102i", "rank": 62, "score": 6.191800117492676}, {"content": "Title: An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus Content: The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV\u2014the Middle East Respiratory Syndrome (MERS)-CoV\u2014was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world\u2019s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.", "qid": 2, "docid": "i9flug4h", "rank": 63, "score": 6.189300060272217}, {"content": "Title: The Twitter Social Mobility Index: Measuring Social Distancing Practices from Geolocated Tweets Content: Social distancing is an important component of the response to the novel Coronavirus (COVID-19) pandemic. Minimizing social interactions and travel reduces the rate at which the infection spreads, and\"flattens the curve\"such that the medical system can better treat infected individuals. However, it remains unclear how the public will respond to these policies. This paper presents the Twitter Social Mobility Index, a measure of social distancing and travel derived from Twitter data. We use public geolocated Twitter data to measure how much a user travels in a given week. We find a large reduction in travel in the United States after the implementation of social distancing policies, with larger reductions in states that were early adopters and smaller changes in states without policies. Our findings are presented on http://socialmobility.covid19dataresources.org and we will continue to update our analysis during the pandemic.", "qid": 2, "docid": "tnecig63", "rank": 64, "score": 6.178800106048584}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Content: Abstract Background and aim As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. Method We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. Results We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. Conclusion In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.", "qid": 2, "docid": "1de98sxz", "rank": 65, "score": 6.161600112915039}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Content: BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.", "qid": 2, "docid": "1tl71xqw", "rank": 66, "score": 6.161599159240723}, {"content": "Title: The Psychological Impact of Confinement Linked to the Coronavirus Epidemic COVID-19 in Algeria Content: The COVID-19 pandemic continues to spread in countries around the world. The impact of this virus is very great on populations following the application of total and partial containment measures. Our study aims to study the psychological impact of total and partial containment applied in Algeria, on 23 March 2020, following the spread of the virus COVID-19 and also studied the habits and behaviors of the Algerian population during this new way of life and this through a cross-sectional survey launched after three days from the start of confinement to quickly assess the impacts over the period from 23 March to 12 April 2020, by an online questionnaire which allowed us to obtain 678 responses from Internet users, who live in confinement in Algeria. According to the gender variable, our sample includes 405 men, or 59.7%, and 273 women, representing 40.3%. The results of the statistical analysis carried out using SPSS version 22.0 software showed that 50.3% of the respondents were in an anxious situation during these first three weeks of confinement. In addition, 48.2% feels stressed, 46.6% of the respondents confirmed to be feeling in a bad mood, and 47.4% do not stop thinking throughout the day about this epidemic and how to protect themselves. In addition, the study shows that 87.9% of the respondents in Algeria found it difficult to follow the confinement instructions. A significant change in the habits of the population was noted especially for the time of going to bed, the time of waking up, and the use of the Internet as well as the hours devoted to daily reading.", "qid": 2, "docid": "2xdz6jj6", "rank": 67, "score": 6.140200138092041}, {"content": "Title: The Europeanization of public health: how does it work? The seminal role of the AIDS case. Content: This article analyzes the path that led the European Union from a somewhat accidental involvement in fighting AIDS to a new and sustainable policy of communicable disease control. It responds to three main questions: Why did an unexpected case lead to the organization of a new sustainable policy? How was this achieved despite national competency over the given policy sector? How did the new policy succeed in covering the enlarged EU? The explanation combines political factors and public health issues. European integration and eastern enlargement made transborder disease management a political necessity. Treaties gave legitimacy to EU policy, while the AIDS matrix furnished the practical procedures: networking, data harmonization, peer-conducted policy coaching, and participation. This pattern of public health management is compatible with national competency, and it is consistent with the democratic values the EU promotes throughout and beyond the enlarged EU. From a theoretical point of view, these patterns of activities constitute the empirically grounded content of the much used but less defined concept of cognitive Europeanization.", "qid": 2, "docid": "62va6ikq", "rank": 68, "score": 6.139999866485596}, {"content": "Title: Anticipating epidemic transitions with imperfect data Content: Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.", "qid": 2, "docid": "bcbqgb2l", "rank": 69, "score": 6.128799915313721}, {"content": "Title: A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread Content: BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.", "qid": 2, "docid": "eiek6olk", "rank": 70, "score": 6.125400066375732}, {"content": "Title: Mass-casualty incidents: how does an ICU prepare? Content: Despite the ever-present risk of mass-casualty incidents (MCIs) in all geographical regions, there is a limited body of literature detailing specifically how an intensive care unit (ICU) prepares for such an event. When responding to an overwhelming volume of severely injured victims, the intensivist must make a paradigm shift away from providing complete care to all patients to one of preferentially administering care to those with the greatest likelihood of survival. To do this effectively, ICU directors must possess a detailed understanding of the entire disaster response, including organization, triage, staffing, and treatment. This article provides a comprehensive review of each of these topics, as well as a framework on specific elements of critical care and treatment based on published literature and expert opinion to assist the clinician in directing care to where it is most appropriate.", "qid": 2, "docid": "pgrhgggn", "rank": 71, "score": 6.120699882507324}, {"content": "Title: Letter: Changes to neurosurgery resident education following onset of the COVID-19 pandemic Content: Abstract Background The COVID-19 pandemic has led to the postponement of a large proportion of neurosurgical cases with an accordant radical change in resident experiences. As residents rely upon operative exposure and in-person didactic lectures for education, the disruptions caused by the pandemic have forced programs to revise how they educate residents. Here we surveyed program directors (PDs) to ascertain how they have altered the education and clinical care responsibilities of residents in response to the COVID-19 pandemic. Methods Surveys were sent to the PDs of all ACGME-accredited neurosurgery programs. Survey questions targeted changes in resident staffing and coverage, changes in didactic material delivery, and changes in resident wellness initiatives. PD concerns were also elicited. Results Of the 116 program PDs invited, 57 responded (49.1%). We found that most programs have reduced resident work weeks (65%) and in-hospital resident shift census (95%). Few have redeployed residents and most are increasingly relying on teleconferencing solutions for meetings and resident education. Most commonly programs are using faculty- (91%) or resident-led (65%) lectures, though nearly 75% are supplementing resident education with materials from the Congress of Neurological Surgeons (CNS). Continuing education in spite of decreased case volume and maintaining resident morale are cited as the most common concerns of PDs. Conclusion Here we find that there is great homogeneity in the responses of neurosurgical residency programs to the COVID-19 pandemic. Programs are increasingly incorporating teleconferencing platforms and third-party education materials, most commonly materials from the CNS. Additionally, most respondents indicated that their program has not redeployed residents in the care of COVID-19 positive patients. The results of the present study may assist program directors in developing a uniform resident curriculum and consider wellness initiatives during this time of crisis.", "qid": 2, "docid": "wa0hdg1u", "rank": 72, "score": 6.096700191497803}, {"content": "Title: Japanese citizens' behavioral changes and preparedness against COVID-19: How effective is Japan's approach of self-restraint? Content: The Japanese government instituted countermeasures against COVID-19, a pneumonia caused by the new coronavirus, in January 2020. Seeking \u201cpeople's behavioral changes,\u201d in which the government called on the public to take precautionary measures or exercise self-restraint, was one of the important strategies. The purpose of this study is to investigate how and from when Japanese citizens have changed their precautionary behavior under these circumstances, where the government has only requested their cooperation. This study uses micro data from a cross-sectional survey conducted on an online platform of an online research company, based on quota sampling that is representative of the Japanese population. By the end of March 2020, we had recruited a total of 11,342 respondents, aged from 20 to 64 years. About 85% reported practising the social distancing recommended by the government. More females than males and more older than younger participants are supportive of practicing social distancing. Frequent handwashing is conducted by 86 percent of all, 92 percent of female and 87.9 percent of over-40 participants. The most important event influencing these precautionary actions was the infection aboard the Diamond Princess cruise ship, which occurred in early February 2020 (23%). Information from the central and local governments, received by 60% of the participants, was deemed trustworthy by 50%. However, the results also showed that about 20% of the participants were reluctant to implement proper prevention measures. The statistical analysis indicated that the typical characteristics of those people were male, younger (under 30 years old), unmarried, from lower-income households, with a drinking or smoking habit and a higher extraversion score. To prevent the spread of infection in Japan, it is imperative to address these individuals and encourage their behavioral changes using various means to reach and influence them.", "qid": 2, "docid": "ttbhg0gp", "rank": 73, "score": 6.095399856567383}, {"content": "Title: The responsibility of healthcare institutions to protect global health security. Content: New public threats that can rapidly cross borders are continuing to challenge global health securityand will require unprecedented levels of co-operation. At the international level, the response to this challenge led to the approval of revised International Health Regulations (IHR). This unanimously approved document outlines how countries are to prepare for and respond to public health emergencies of international concern in a manner that does not unnecessarily impact on travel and trade.", "qid": 2, "docid": "rebll0rk", "rank": 74, "score": 6.086100101470947}, {"content": "Title: Data-Driven Classifiers for Predicting Grass Growth in Northern Ireland: A Case Study Content: There are increasing pressures to combat climate change and improve sustainable land management. The agriculture industry is one of the most challenging areas for these changes, especially in Northern Ireland, as agriculture is one of the larger industries. Research has been carried out across the island of Ireland into methods of improving farm efficiency in multiple areas of farming, including livestock health, machinery improvements, and crop growth. Research has been carried out in this study into grass growth in the dairy farming sector, specifically within Northern Ireland. Grass growth prediction aims to inform farmers and policy makers in their decision-making process regarding sustainable land management in agriculture. The present work focuses on analysing and evaluating how data-driven classifiers can be used for grass growth prediction using the data related to soil content, weather, grass quality components etc. Four classifiers, namely Decision Trees, Random Forest, Na\u00efve Bayes, and Neural Networks, are chosen for this purpose. Classification results based on a real-world data set are analysed and compared to evaluate and illustrate the performance and robustness of the classifiers. The results indicate that it is difficult to declare a single classifier with the highest performance and robustness. Nevertheless, it indicates that tree classification methods are better suited to the data to be studied, as opposed to probabilistic methods and weighted methods, e.g., the na\u00efve Bayes classifier obtained a predictive performance of 78% when classifying spring seasonal grass growth data.", "qid": 2, "docid": "xanp9nbu", "rank": 75, "score": 6.075799942016602}, {"content": "Title: Scientia Potentia Est: How the Italian World of Oncology Changes in the COVID-19 Pandemic. Content: PURPOSE After coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. The COVID-19 pandemic has required oncologists to redefine clinical organization and patient management. The purpose of our study was to document the difficulties emerging during the SARS-CoV-2 pandemic in Italian oncology. METHODS We broadcasted an electronic survey to oncologic health care professionals. It consisted of 45 questions ranging from individual perception of pandemic management by hospital centers to physicians' and nurses' psychological distress and patient care. RESULTS A total of 383 oncology health workers participated in the survey. The majority were female (71.8%) and from central Italy (46.2%). Impressively, a total of 357 (93%) participants declared the oncologic department reorganized routine clinical activity, but only 40.5% were adequately trained about the required procedures; 20% of the survey respondents think they have not received adequate and timely protective devices. CONCLUSION Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks have emerged from the first analyses investigating how the world of oncology changes in the COVID-19 pandemic. Information, protection, testing, and training of health care professionals are key words that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the future.", "qid": 2, "docid": "hjyaqmyl", "rank": 76, "score": 6.072199821472168}, {"content": "Title: Scientia Potentia Est: How the Italian World of Oncology Changes in the COVID-19 Pandemic Content: PURPOSE: After coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. The COVID-19 pandemic has required oncologists to redefine clinical organization and patient management. The purpose of our study was to document the difficulties emerging during the SARS-CoV-2 pandemic in Italian oncology. METHODS: We broadcasted an electronic survey to oncologic health care professionals. It consisted of 45 questions ranging from individual perception of pandemic management by hospital centers to physicians' and nurses' psychological distress and patient care. RESULTS: A total of 383 oncology health workers participated in the survey. The majority were female (71.8%) and from central Italy (46.2%). Impressively, a total of 357 (93%) participants declared the oncologic department reorganized routine clinical activity, but only 40.5% were adequately trained about the required procedures; 20% of the survey respondents think they have not received adequate and timely protective devices. CONCLUSION: Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks have emerged from the first analyses investigating how the world of oncology changes in the COVID-19 pandemic. Information, protection, testing, and training of health care professionals are key words that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the future.", "qid": 2, "docid": "v0zpdwr4", "rank": 77, "score": 6.072198867797852}, {"content": "Title: The Stirling Protocol \u2013 Putting the environment at the heart of prosperity and social inclusion Content: Abstract While the global coronavirus crisis impacts society and the economy in a myriad of ways, it provides, what is likely to be, a once in a lifetime opportunity for us to rethink our response to climate change. According to the 2020 Global Risk Register, extreme weather and climate action failure are the two most likely and impactful risks to the global economy, which now more than ever needs to be avoided. Addressing the major challenges that we face from climate change can often appear to conflict with economic priorities. Add to this the fact that environmental mitigation steps can inadvertently exclude sections of the population and the enormity and complexity of climate change responses can result in paralysis. In contrast, the Stirling Protocol provides the framework for rapid, effective action and comprises three pillars: Environment, Economy & Inclusion. By addressing and balancing these three pillars, the simple protocol can be adopted throughout organisations putting the environment at the heart of sustainable prosperity and inclusion and provide a benchmark for positive action.", "qid": 2, "docid": "g8grcy5j", "rank": 78, "score": 6.037300109863281}, {"content": "Title: COVID-19: Effects of weather conditions on the propagation of respiratory droplets Content: As the number of confirmed cases of Coronavirus disease 2019 (COVID-19) continues to increase, there has been a rising concern regarding the effect of weather conditions, especially over the upcoming summer, on the transmission of this disease. In this study, we assess the transmission of COVID-19 under different weather conditions by investigating the propagation of infectious respiratory droplets. A comprehensive mathematical model is established to explore their evaporation, heat transfer and kinematics under different temperature, humidity and ventilation conditions. The transmitting pathway of COVID-19 through respiratory droplets is divided into short-range droplet contacts and long-range aerosol exposure. We show that the effect of weather conditions is not monotonic: low temperature and high humidity facilitate droplet contact transmission, while high temperature and low humidity promote the formation of aerosol particles and accumulation of particles with a diameter of 2.5 m or less (PM2.5). Our model suggests that the 6 ft of social distance recommended by the Center for Disease Control and Prevention (CDC) may be insufficient in certain environmental conditions, as the droplet spreading distance can be as long as 6 m (19.7 ft) in cold and humid weather. The results of this study suggest that the current pandemic may not ebb in the summer of the northern hemisphere without proper intervention, as there is an increasing chance of aerosol transmission. We also emphasize that the meticulous design of building ventilation systems is critical in containing both the droplet contact infections and aerosol exposures.", "qid": 2, "docid": "tyhtdawb", "rank": 79, "score": 6.000999927520752}, {"content": "Title: Key Strategies for Clinical Management and Improvement of Healthcare Services for Cardiovascular Disease and Diabetes Patients in the Coronavirus (COVID-19) Settings: Recommendations From the REPROGRAM Consortium Content: Patients with cardiovascular disease and diabetes are at potentially higher risk of infection and fatality due to COVID-19. Given the social and economic costs associated with disability due to these conditions, it is imperative that specific considerations for clinical management of these patients be observed. Moreover, the reorganization of health services around the pandemic response further exacerbates the growing crisis around limited access, treatment compliance, acute medical needs, and mental health of patients in this specific subgroup. Existing recommendations and guidelines emanating from respective bodies have addressed some of the pressure points; however, there are variations and limitations vis a vis patient with multiple comorbidities such as obesity. This article will pull together a comprehensive assessment of the association of cardiovascular disease, diabetes, obesity and COVID-19, its impact on the health systems and how best health systems can respond to mitigate current challenges and future needs. We anticipate that in the context of this pandemic, the cardiovascular disease and diabetes patients need a targeted strategy to ensure the harm to this group does not translate to huge costs to society and to the economy. Finally, we propose a triage and management protocol for patients with cardiovascular disease and diabetes in the COVID-19 settings to minimize harm to patients, health systems and healthcare workers alike.", "qid": 2, "docid": "iu2rgpb0", "rank": 80, "score": 5.995100021362305}, {"content": "Title: Does lockdown reduce air pollution? Evidence from 44 cities in northern China Content: Abstract Responding to the ongoing novel coronavirus (agent of COVID-19) outbreak, China implemented \u201cthe largest quarantine in human history\u201d in an attempt to prevent the spread of the virus on 23 January 2020. Human mobility and relevant production and consumption activities have since decreased significantly. As a likely side effect of this decrease, many regions have recorded significant reductions in air pollution. We employed daily air pollution data and Intracity Migration Index (IMI) data form Baidu between 1 January and 21 March 2020 for 44 cities in northern China to examine whether, how, and to what extent travel restrictions affected air quality. On the basis of this quantitative analysis, we reached the following conclusions: (1) The reduction of air pollution was strongly associated with travel restrictions during this pandemic\u2014on average, the air quality index (AQI) decreased by 7.80%, and five air pollutants (i.e., SO2, PM2.5, PM10, NO2, and CO) decreased by 6.76%, 5.93%, 13.66%, 24.67%, and 4.58%, respectively. (2) Mechanism analysis illustrated that the lockdowns of 44 cities reduced human movements by 69.85%, and a reduction in the AQI, PM2.5, and CO was partially mediated by human mobility, and SO2, PM10, and NO2 were completely mediated. (3) Our findings highlight the importance of understanding the role of green production and consumption.", "qid": 2, "docid": "wadta686", "rank": 81, "score": 5.995099067687988}, {"content": "Title: Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns Content: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)\u2014where the virus first broke out in December and spread widely from January to February 2020\u2014was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 \u00b0C and 12 \u00b0C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4\u201312 \u00b0C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "qid": 2, "docid": "26gf4q1v", "rank": 82, "score": 5.99399995803833}, {"content": "Title: How to deal with the negative psychological impact of COVID-19 for people who pay attention to anxiety and depression Content: BACKGROUND: The fear of insecurity and uncertainty caused by 2019 coronavirus disease (COVID-19), the separation and loss of certain important relationships, and the great changes in lifestyle have awakened strong emotional response, which may cause psychological problems to the general population. However, there are few researches on how the people who pay attention to anxiety and depression coping with negative psychological during the epidemic or major disaster. This study aimed to identify what behaviors can effectively reduce negative emotions during the epidemic. METHODS: From February 1, to March 8 in 2020, we conducted a web-based survey and collected information on general demographic data. The probable depression, anxiety symptoms and coping behaviors was assessed by Patient Health Questionnaire-9 and Generalized anxiety disorder-7 and the self-made Coping Behaviors Questionnaires. RESULT: Among 17249 responders, 7923 and 9326 completed the assessment of depression and anxiety respectively, and all responders finished the assessment of the coping behaviors questionnaires. Our survey population had a high prevalence rate of possible depression disorders and anxiety disorders were34.66% and 56.93%, respectively. Those who are old, female, low education, low income, and cohabiting were more likely to suffer depression and/or anxiety. Students are a high-risk group suffering from depression and/or anxiety. After adjusting for social-demographic factors (e.g. age, sex), depression and anxiety were positively associated with self-injury, doing housework, and having sex or masturbating and negatively associated with singing, drawing, or writing, dating friends online, singing, attending lectures, and doing yoga. CONCLUSION: During the epidemic, our findings identify some spontaneous coping behaviors that can probably relieve the psychological impact of vulnerable groups during the COVID-19 epidemic.", "qid": 2, "docid": "cdxpodfg", "rank": 83, "score": 5.971799850463867}, {"content": "Title: Voluntary Cyclical Distancing: A potential alternative to constant level mandatory social distancing, relying on an 'infection weather report' Content: COVID-19 has significantly changed our daily lives. Stay-at-home orders and forced closings of all non-essential businesses has had a significant impact on our economy. While it is important to ensure that the healthcare system is not overwhelmed, there are many questions that remain about the efficacy of extreme social distancing, and whether there are alternatives to mandatory lockdowns. This paper analyzes the utility of various levels of social distancing, and suggests an alternative approach using voluntary distancing informed by an infectious load index or 'infection weather report.'", "qid": 2, "docid": "xcfk4efo", "rank": 84, "score": 5.968800067901611}, {"content": "Title: Zoonotic disease risk perceptions in the British veterinary profession Content: Abstract In human and veterinary medicine, reducing the risk of occupationally-acquired infections relies on effective infection prevention and control practices (IPCs). In veterinary medicine, zoonoses present a risk to practitioners, yet little is known about how these risks are understood and how this translates into health protective behaviour. This study aimed to explore risk perceptions within the British veterinary profession and identify motivators and barriers to compliance with IPCs. A cross-sectional study was conducted using veterinary practices registered with the Royal College of Veterinary Surgeons. Here we demonstrate that compliance with IPCs is influenced by more than just knowledge and experience, and understanding of risk is complex and multifactorial. Out of 252 respondents, the majority were not concerned about the risk of zoonoses (57.5%); however, a considerable proportion (34.9%) was. Overall, 44.0% of respondents reported contracting a confirmed or suspected zoonoses, most frequently dermatophytosis (58.6%). In veterinary professionals who had previous experience of managing zoonotic cases, time or financial constraints and a concern for adverse animal reactions were not perceived as barriers to use of personal protective equipment (PPE). For those working in large animal practice, the most significant motivator for using PPE was concerns over liability. When assessing responses to a range of different \u201cinfection control attitudes\u201d, veterinary nurses tended to have a more positive perspective, compared with veterinary surgeons. Our results demonstrate that IPCs are not always adhered to, and factors influencing motivators and barriers to compliance are not simply based on knowledge and experience. Educating veterinary professionals may help improve compliance to a certain extent, however increased knowledge does not necessarily equate to an increase in risk-mitigating behaviour. This highlights that the construction of risk is complex and circumstance-specific and to get a real grasp on compliance with IPCs, this construction needs to be explored in more depth.", "qid": 2, "docid": "0tun7fjk", "rank": 85, "score": 5.964600086212158}, {"content": "Title: The nexus between COVID-19, temperature and exchange rate in Wuhan city: New findings from partial and multiple wavelet coherence Content: This study attempts to document the nexus between weather, COVID-19 outbreak in Wuhan and the Chinese economy. We used daily average temperature (hourly data), daily new confirmed cases of COVID-19 in Wuhan, and RMB (Chinese currency) exchange rate to represent the weather, COVID-19 outbreak and the Chinese economy, respectively. The methodology of Wavelet Transform Coherence (WTC), Partial Wavelet Coherence (PWC) and Multiple Wavelet Coherence (MWC) is employed to analyze the daily data collected from 21st January 2020 to 31st March 2020. The results have revealed a significant coherence between the series at different time-frequency combinations. The overall results suggest the insignificance of an increase in temperature to contain or slow down the new COVID-19 infections. The RMB exchange rate and the COVID-19 showed an out phase coherence at specific time-frequency spots suggesting a negative but limited impact of the COVID-19 outbreak in Wuhan on the Chinese export economy. Our results are contrary to many earlier studies which suggest a significant role of temperature in slowing down the COVID-19 spread. These results can have important policy implications for the containment of COVID-19 spread and macro-economic management with respect to changes in the weather.", "qid": 2, "docid": "cx3lf0dx", "rank": 86, "score": 5.963900089263916}, {"content": "Title: How did general practitioners protect themselves, their family, and staff during the SARS epidemic in Hong Kong? Content: CONTEXT Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease and how the frontline community doctors respond to it is not known. OBJECTIVES To explore the impact of SARS on general practitioners (GPs) in Hong Kong. DESIGN A cross sectional survey. SETTING Community based primary care clinics. PARTICIPANTS 183 family medicine tutors affiliated with a local university. Postal survey sent to all tutors with a 74.8% response rate. MAIN OUTCOME MEASURES Change of clinical behaviour and practices during the epidemic; anxiety level of primary care doctors. RESULTS All agreed SARS had changed their clinical practices. Significant anxiety was found in family doctors. Three quarters of respondents recalled requesting more investigations while a quarter believed they had over-prescribed antibiotics. GPs who were exposed to SARS or who had worked in high infection districts were less likely to quarantine themselves (10.8% versus 33.3%; p<0.01; 6.5% versus 27.5%; p<0.01 respectively). Exposure to SARS, the infection rates in their working district, and anxiety levels had significant impact on the level of protection or prescribing behaviour. CONCLUSION The clinical practice of GPs changed significantly as a result of SARS. Yet, those did not quarantine themselves suggesting other factors may have some part to play. As failure to apply isolation precautions to suspected cases of SARS was one major reason for its spread, a contingency plan from the government to support family doctors is of utmost importance. Interface between private and public sectors are needed in Hong Kong to prepare for any future epidemics.", "qid": 2, "docid": "z40j06sy", "rank": 87, "score": 5.956999778747559}, {"content": "Title: Impact of weather indicators on the COVID-19 outbreak: A multi-state study in India Content: The present study examines the impact of weather indicators on the COVID-19 outbreak in the majorly affected states of India. In this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. The Kendall and Spearman rank correlation tests were chosen to conduct the statistical analysis. In this regard, we compiled a daily dataset including confirmed case counts, Recovered case counts, Deceased cases, Average Temperature, Maximum Relative Humidity, Maximum Wind Speed for six most affected states of India during the period of March 25, 2020 to April 24, 2020. We investigated that the average Humidity and Average Temperature seven days ago play a significant role in the recovery of coronavirus cases. The rise in average temperature will improve the recovery rate in the days to come. The cities with very high humidity levels or dry weather conditions have high probabilities of recovery from COVID-19. The findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures.", "qid": 2, "docid": "yi57n8nc", "rank": 88, "score": 5.954500198364258}, {"content": "Title: Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns Content: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)-where the virus first broke out in December and spread widely from January to February 2020-was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 &#8728; C and 12 &#8728; C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4-12 &#8728; C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "qid": 2, "docid": "04rbtmmi", "rank": 89, "score": 5.942500114440918}, {"content": "Title: Extreme temperature event and mass mortality of insectivorous bats Content: A mass mortality event involving Chaerephon plicatus and Taphozous theobaldi bats occurred during a heat wave in April 2016 in Cambodia. This was investigated to clarify the causes of the die-off and assess the risk to public health. Field evidences, clinical signs, and gross pathology findings were consistent with a heat stress hypothesis. However, the detection of a novel bat paramyxovirus raises questions about its role as a contributing factor or a coincidental finding. Systematic documentation of bat die-offs related to extreme weather events is necessary to improve understanding of the effect of changing weather patterns on bat populations and the ecosystem services they provide.", "qid": 2, "docid": "9tqivs5f", "rank": 90, "score": 5.939799785614014}, {"content": "Title: Evolution of practice gaps in gastrointestinal and endoscopic surgery: 2012 report from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Continuing Education Committee. Content: BACKGROUND In an effort to fulfill its charge to develop and maintain a comprehensive educational program to serve the members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the SAGES Continuing Education Committee (CEC) reports a summary of findings related to its evaluation of the 2012 SAGES annual meeting. METHODS All attendees to the 2012 annual meeting had the opportunity to complete an immediate postmeeting questionnaire as part of their continuing medical education (CME) certification in which they identified up to two learning themes, answered questions related to potential practice change items that are based on those learning themes, and complete a needs assessment related to important learning topics for future meetings. In addition, participants in the postgraduate and hands-on courses were asked to complete questions about case volume and comfort levels related to procedures/topics in those courses. All respondents to this initial survey were sent a 3-month follow-up questionnaire in which they were asked how successfully they had implemented the intended practice changes and what, if any, barriers they encountered. Postgraduate and hands-on course participants completed case volume and comfort level questions. Descriptive statistical analysis of this deidentified data was undertaken. RESULTS Response rates were 42% and 56% for CME-eligible attendees/respondents for the immediate postmeeting and 3-month follow-up questionnaires, respectively. Top learning themes for respondents were Bariatric, Hernia, Foregut, and Colorectal. Improving minimally invasive surgical (MIS) technique and managing complications related to MIS procedures were top intended practice changes. Partial implementation was common with top barriers including cost restrictions, lack of institutional support, and lack of time. CONCLUSIONS The 2012 annual meeting analysis provides insight into educational needs among respondents and will help with planning content for future meetings.", "qid": 2, "docid": "x1bp6o8v", "rank": 91, "score": 5.934000015258789}, {"content": "Title: Impact of weather on COVID-19 pandemic in Turkey Content: The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (\u00b0C), dew point (\u00b0C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1\u00e2\u0080\u00afday to 14\u00e2\u0080\u00afdays. Therefore, the effects of each parameter within 1, 3, 7, and 14\u00e2\u0080\u00afdays are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14\u00e2\u0080\u00afdays ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "qid": 2, "docid": "ds3nmssp", "rank": 92, "score": 5.913899898529053}, {"content": "Title: Impact of weather on COVID-19 pandemic in Turkey Content: Abstract The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (\u00b0C), dew point (\u00b0C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "qid": 2, "docid": "jxa9h27b", "rank": 93, "score": 5.913898944854736}, {"content": "Title: Managing business relationships during a pandemic: Conducting a relationship audit and developing a path forward Content: Abstract During stable times, firms will generally aim to create reliable B2B relationships that provide increased efficiency and profitability. However, tumultuous times, such as the time during a major pandemic, cause many significant disruptions in both internal and external environmental domains. Thus, we argue that it is critical during this time to reevaluate the company's business relationships as a whole. While long-term partnerships are great for handling incremental changes during stable times, disruptive environmental changes may require managers to consider disruptive changes to their businesses. A pandemic may also present opportunities for establishing new relationships as there may be other partners/suppliers who are better equipped to help the company address urgent short-term needs and to capitalize on significant long-term opportunities. In this paper, we design a new relationship audit template to help B2B firms weather the immediate crisis at hand and position themselves more strategically for the future. We explore this idea in relation to the coronavirus outbreak, introduce the idea of a B2B crisis relationship audit, and offer potential steps forward for firms.", "qid": 2, "docid": "0mikqjpj", "rank": 94, "score": 5.9131999015808105}, {"content": "Title: Emerging coordination and knowledge transfer process during disease outbreak Content: When multiple agencies respond to a disease outbreak (i.e., H1N1 and SARS), the coordination of actions is complex and evolves over time. There has not been any systematic empirical study of the dynamics of emerging coordination behaviour and knowledge transfer process during a disease outbreak. In this paper, we first introduce our approach for the analysis of multi-agency intervention during a disease outbreak using the study of social networks. Using social networks and its analytic framework, we explore questions such as: How does the multi-agency coordination emerge for supporting the complex knowledge transfer process during different phases of disease outbreak? How effective are these formal and informal coordination mechanisms in achieving a robust outcome in response coordination through effective knowledge transfer process during the outbreak? What are the key lessons learned by studying the emerging coordination and knowledge transfer process during past disease outbreak in improving the multi-agency preparedness for dealing with future outbreaks? The discussion is supported by a qualitative study of the implementation of the results of the analysis. We reveal that profound understanding of social network behaviour and emerging coordination concepts are pivotal to the optimisation of knowledge transfer process which is a prerequisite for successful outbreak intervention. We look qualitatively at how Hunter New England Area Health Services applied these concepts to lead a successful coordination plan during an H1N109 endemic.", "qid": 2, "docid": "x6re8787", "rank": 95, "score": 5.899199962615967}, {"content": "Title: Warmer weather and global trends in the coronavirus COVID-19 Content: Predicting COVID-19 epidemic development in the upcoming warm season has attracted much attention in the hope of providing helps to fight the epidemic. It requires weather (environmental) factors to be included in prediction models, but there are few models to achieve it successfully. In this study, we proposed a new concept of environmental infection rate (RE), based on floating time of respiratory droplets in the air and inactivation rate of virus to solve the problem. More than half of the particles in the droplets can float in the atmosphere for 1-2 hours. The prediction results showed that high RE values (>3.5) are scattered around 30N in winter (Dec.-Feb.). As the weather warms, its distribution area expands and extends to higher latitudes of northern hemisphere, reaching its maximum in April, and then shrinking northward. These indicated that the spread of COVID-19 in most parts of the northern hemisphere is expected to decline after Apr., but the risks in high latitudes will remain high in May. In the south of southern hemisphere, the RE values tend to subside from Apr. to July. The high modeled RE values up to July, however, suggested that warmer weather will not stop COVID-19 from spreading. Public health intervention is needed to overcome the outbreak.", "qid": 2, "docid": "fj3a2y1o", "rank": 96, "score": 5.8856000900268555}, {"content": "Title: Leveraging a Bayesian Network approach to model and analyze supplier vulnerability to severe weather risk: A case study of the U.S. pharmaceutical supply chain following Hurricane Maria Content: Abstract The United States government has identified the health care sector as part of the critical infrastructure for homeland security to protect citizens against health risks arising from terrorism, natural disasters, and epidemics. Citizens also have expectations about the role that health care plays in enjoying a good quality of life, by providing response systems to handle emergencies and other illness situations adequately. Among the systems required to support desired performance levels is a robust and resilient pharmaceutical supply chain that is free of disruption. Shortages of drugs place undue pressure on healthcare providers to devise alternative approaches to administer patient care. With climate change expected to result in increasingly severe weather patterns in the future, it is critical that logistics engineers understand the impact that a catastrophic weather event could have on supply chain disruption to facilitate the design of supply systems that are robust and resilient. This study investigates the main causal and intermediate events that led to risk propagation in, and disruption of, the U.S. pharmaceutical supply chain following Hurricane Maria. A causality Bayesian model is developed to depict linkages between risk events and quantify the associated cumulative risk. The quantification is further examined through different advanced techniques such as predictive inference reasoning and sensitivity analysis. The general interpretation of these analyses suggests that port resilience is imperative to pharmaceutical supply chain performance in the case of Puerto Rico.", "qid": 2, "docid": "94xsyvux", "rank": 97, "score": 5.879799842834473}, {"content": "Title: People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior Content: Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.", "qid": 2, "docid": "pl2d1yc0", "rank": 98, "score": 5.877699851989746}, {"content": "Title: Social scientists scramble to study pandemic, in real time Content: If pandemic lockdowns have people feeling a bit like lab rats stuck in cages, in some ways that\u2019s exactly what they are As the coronavirus touches on virtually every part of life around the globe, social scientists are rushing to suck up real-time data on how people are responding to the unfolding pandemic Economists are gathering data about supply chains Political scientists are scrutinizing how government responses track with ideology Psychologists are monitoring children in after-school programs Behavioral scientists are surveying thousands of people to see how they respond to information in a crisis", "qid": 2, "docid": "h043j0wa", "rank": 99, "score": 5.877200126647949}, {"content": "Title: Does lockdown reduce air pollution? Evidence from 44 cities in northern China Content: Responding to the ongoing novel coronavirus (agent of COVID-19) outbreak, China implemented \"the largest quarantine in human history\" in Wuhan on 23 January 2020. Similar quarantine measures were imposed on other Chinese cities within days. Human mobility and relevant production and consumption activities have since decreased significantly. As a likely side effect of this decrease, many regions have recorded significant reductions in air pollution. We employed daily air pollution data and Intracity Migration Index (IMI) data form Baidu between 1 January and 21 March 2020 for 44 cities in northern China to examine whether, how, and to what extent travel restrictions affected air quality. On the basis of this quantitative analysis, we reached the following conclusions: (1) The reduction of air pollution was strongly associated with travel restrictions during this pandemic-on average, the air quality index (AQI) decreased by 7.80%, and five air pollutants (i.e., SO2, PM2.5, PM10, NO2, and CO) decreased by 6.76%, 5.93%, 13.66%, 24.67%, and 4.58%, respectively. (2) Mechanism analysis illustrated that the lockdowns of 44 cities reduced human movements by 69.85%, and a reduction in the AQI, PM2.5, and CO was partially mediated by human mobility, and SO2, PM10, and NO2 were completely mediated. (3) Our findings highlight the importance of understanding the role of green production and consumption.", "qid": 2, "docid": "3suti99o", "rank": 100, "score": 5.8557000160217285}]}
{"query": "will SARS-CoV2 infected people develop immunity? Is cross protection possible?", "hits": [{"content": "Title: Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors Content: The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the \u2018cytokine storm\u2019, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1\u03b2, IL-6 and TNF-\u03b1 secretion via \u2018trained monocytes\u2019, which confers early protection against SARS-CoV2.", "qid": 3, "docid": "6dq6gm27", "rank": 1, "score": 11.408499717712402}, {"content": "Title: SARS Cov2 infection in a renal transplanted patients. A case report. Content: The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can \"be protective\" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.", "qid": 3, "docid": "2c4jk2ms", "rank": 2, "score": 10.782699584960938}, {"content": "Title: Clinical exacerbation of SARS-CoV2 infection after fingolimod withdrawal Content: The role of disease-modifying therapies in patients with autoimmune disorders during SARS-CoV2 infection is controversial. Immunocompromised patients could have a more severe COVID-19 disease, due to the absence of an adequate immune response against the SARS-CoV-2. However, therapies that act on immune response could play a protective role by dampening the cytokine release syndrome. Fingolimod is a drug used for immune therapy in patients with Multiple Sclerosis (MS) through the sequestration of activated lymphocytes in the lymph nodes. We report the case of a 57-year-old man with relapsing-remitting MS treated with fingolimod that showed a reactivation of COVID-19 with signs of hyperinflammation syndrome after fingolimod withdrawal. Our case suggests that discontinuation of fingolimod during COVID-19 could imply a worsening of SARS-CoV2 infection. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "kapv6sye", "rank": 3, "score": 10.471099853515625}, {"content": "Title: Clinical exacerbation of SARS\u2010CoV2 infection after fingolimod withdrawal Content: The role of disease\u2010modifying therapies in patients with autoimmune disorders during SARS\u2010CoV2 infection is controversial. Immunocompromised patients could have a more severe COVID\u201019 disease, due to the absence of an adequate immune response against the SARS\u2010CoV\u20102. However, therapies that act on immune response could play a protective role by dampening the cytokine release syndrome. Fingolimod is a drug used for immune therapy in patients with Multiple Sclerosis (MS) through the sequestration of activated lymphocytes in the lymph nodes. We report the case of a 57\u2010year\u2010old man with relapsing\u2010remitting MS treated with fingolimod that showed a reactivation of COVID\u201019 with signs of hyperinflammation syndrome after fingolimod withdrawal. Our case suggests that discontinuation of fingolimod during COVID\u201019 could imply a worsening of SARS\u2010CoV2 infection. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "sg55s5nv", "rank": 4, "score": 10.471098899841309}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \u201coriginal antigenic sin.\u201d The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 3, "docid": "7k24r3p5", "rank": 5, "score": 10.442399978637695}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \"original antigenic sin.\" The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 3, "docid": "nacxjt2f", "rank": 6, "score": 10.442399024963379}, {"content": "Title: The case for Chronotherapy in COVID\u201019 induced Acute Respiratory Distress Syndrome (ARDS). Content: COVID\u201019, the disease resulting from infection by a novel coronavirus: SARS\u2010Cov2 that has rapidly spread since November 2019 leading to a global pandemic. SARS\u2010Cov2 has infected over 4 million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of Acute Respiratory Distress Syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti\u2010inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS and thus chronotherapy may be used to effectively manage ARDS in COVID\u201019 patients.", "qid": 3, "docid": "7gqzyzjz", "rank": 7, "score": 10.384300231933594}, {"content": "Title: The case for chronotherapy in Covid-19-induced acute respiratory distress syndrome Content: Coronavirus disease 2019 (COVID-19), the disease resulting from infection by a novel coronavirus, SARS-Cov2, has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over four million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of acute respiratory distress syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS, and thus, chronotherapy may be used to effectively manage ARDS in COVID-19 patients.", "qid": 3, "docid": "behe7zl6", "rank": 8, "score": 10.384299278259277}, {"content": "Title: New IgM seroconversion and positive RT\u2010PCR test after exposure to the virus in recovered COVID\u201019 patient Content: To date, understanding whether acquired immunity and presence of anti SARS\u2010Cov2 antibodies protects against reinfection is one the most important focus of the scientific community [1\u20102]. Several studies suggest that acquired immunity may protect upon further exposure to SARS\u2010COV2 [3\u20106]. Contrary to this picture, we describe a case of a patient recovered from COVID\u201019 pneumonia with positive serology, followed up by 6 negative nasopharyngeal swab\u2010PCR tests performed along 1 month, who later on, after exposure to the virus, presented another positive RT\u2010PCR test and a second IgM seroconversion. This report opens up several possible interpretations. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "38mhmxvd", "rank": 9, "score": 10.368300437927246}, {"content": "Title: COVID\u201019 is milder in children possibly due to cross immunity Content: It has been unclear why the new severe acute respiratory syndrome coronavirus (sars\u2010CoV\u20102) hits a small minority hard, while the vast majority of children appear to be protected and develop mild or no disease (1,2). The editorial by Brodin suggests some possible mechanisms why it is so (1). I would like to emphasize the significance of cross immunity due to previous exposure to seasonal coronavirus; it may be a plausible explanation for why children appear to be protected (2,3).", "qid": 3, "docid": "wfftfkam", "rank": 10, "score": 10.245800018310547}, {"content": "Title: Revisi\u00f3n Narrativa Sobre La Respuesta Inmunitaria Frente A Coronavirus: Descripci\u00f3n General, Aplicabilidad Para Sars-Cov2 E Implicaciones Terap\u00e9uticas Content: Abstract The new coronavirus (SARS-CoV2) that causes a severe acute respiratory syndrome emerged in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and it applicability to SARS-CoV2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.", "qid": 3, "docid": "rq5nqm92", "rank": 11, "score": 10.241600036621094}, {"content": "Title: Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms Content: The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities.Communicated by Ramaswamy H. Sarma.", "qid": 3, "docid": "osjyyz1e", "rank": 12, "score": 10.14490032196045}, {"content": "Title: Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus. Content: Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopovo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract--the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils (near the distal end of the tract), rectum and cloaca (the common opening for release of eggs and faeces), usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks do not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced alphabeta T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.", "qid": 3, "docid": "94dughd1", "rank": 13, "score": 10.101499557495117}, {"content": "Title: Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus Content: Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopavo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, Severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract\u2014the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils, rectum and cloaca, usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks may not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced \u03b1\u03b2 T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.", "qid": 3, "docid": "fdkwklzj", "rank": 14, "score": 10.1014986038208}, {"content": "Title: Ebselen as a highly active inhibitor of PLProCoV2 Content: Since December 2019 a novel a coronavirus identified as SARS-CoV-2 or COV2 has been spreading around the world. On the 16th of May around 4.5 million people got infected and over 300,000 died due to the infection of COV2. The effective treatment remains a challenge. Targeted therapeutics are still under investigation. The papain-like protease (PLPro) from the human SARS-CoV-2 coronavirus is a cysteine protease that plays a critical role in virus replication. Its activity is required to process the viral polyprotein into functional, mature subunits. Moreover, COV2 uses this enzyme to modulate the host\u2019s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity in mammalian cells and cytotoxicity in lower organisms, is a highly active inhibitor of PLProCoV2. We proved that ebselen is a covalent, fast-binding inhibitor of PLProCoV2 exhibiting a low micromolar potency. Furthermore, we identified a difference between PLPro from SARS-CoV-1 (the corona virus which caused the 2002\u20132004 outbreak, SARS) and SARS-CoV-2 that allows to explain the difference in dynamics of the replication, and, thus, the disease progression. Namely, we present that they show differences in the binding affinity of substrates that we observed through kinetics and molecular docking studies. Using a novel Approximate Bayesian Computation method we were able to find kinetic constants for both enzymes. Molecular modeling study on the structure of the active site and binding mode of the ebselen with SARS and COV2 showed also significant differences that could explain our observation that ebselen is less active and slower bounding with SARS than COV2. In conclusion, we show that ebselen inhibits the activity of the essential viral enzyme papain-like protease (PLpro) from SARS-COV-2 in low micromolar range.", "qid": 3, "docid": "51n5mnjb", "rank": 15, "score": 10.059000015258789}, {"content": "Title: Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic. Content: In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland.", "qid": 3, "docid": "kbyf6u49", "rank": 16, "score": 10.044899940490723}, {"content": "Title: Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic Content: In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland.", "qid": 3, "docid": "p5h752r6", "rank": 17, "score": 10.044898986816406}, {"content": "Title: Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV2 Content: Background The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5\u2019 and 3\u2019 untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon. Methods To have an idea of the global changes in 5\u2019 and 3\u2019-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by \u2018RBPmap\u2019 and \u2018RNA22 v2\u2019 respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue. Results We identified 28 unique variants in SARS-CoV2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5\u2019-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3\u2019UTR among most of the continents. Furthermore, we found that despite of the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs. Conclusion Our results, shows for the first time in SARS-Cov2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.", "qid": 3, "docid": "qp16o05y", "rank": 18, "score": 10.043999671936035}, {"content": "Title: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming Content: Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2\u2032) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2\u2032 cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.", "qid": 3, "docid": "j1370ljf", "rank": 19, "score": 10.009200096130371}, {"content": "Title: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming Content: Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2') cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2' cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.", "qid": 3, "docid": "vn3ugk4f", "rank": 20, "score": 10.009199142456055}, {"content": "Title: Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms Content: The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities. Communicated by Ramaswamy H. Sarma", "qid": 3, "docid": "mx92p318", "rank": 21, "score": 9.993499755859375}, {"content": "Title: A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Content: The possibility of antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection have the theoretical potential to amplify viral infections or trigger immunopathology. Observations relevant to the risks of ADE of disease require careful review at this critical point in the SARS-CoV-2 pandemic. At present, no clinical findings, immunologic assays or biomarkers are known to differentiate any severe viral infection from immune-enhanced disease, whether by antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same, and designing animal models depends on understanding how antiviral host responses may become harmful in people. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, since we cannot predict ADE of disease reliably after either vaccination or treatment with antibodies, regardless of what virus is the causative agent, it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 disease move forward.", "qid": 3, "docid": "x73moqog", "rank": 22, "score": 9.95009994506836}, {"content": "Title: Immunization with the receptor\u2013binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement Content: Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.", "qid": 3, "docid": "ygwdldae", "rank": 23, "score": 9.839300155639648}, {"content": "Title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients Content: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients.", "qid": 3, "docid": "qpbgq5d8", "rank": 24, "score": 9.798299789428711}, {"content": "Title: Structural Similarity of SARS-CoV2 Mpro and HCV NS3/4A Proteases Suggests New Approaches for Identifying Existing Drugs Useful as COVID-19 Therapeutics. Content: During the current COVID-19 pandemic more than 160,000 people have died worldwide as of mid-April 2020, and the global economy has been crippled. Effective control of the SARS-CoV2 virus that causes the COVID-19 pandemic requires both vaccines and antivirals. Antivirals are particularly crucial to treat infected people during the period of time that an effective vaccine is being developed and deployed. Because the development of specific antiviral drugs can take a considerable length of time, an important approach is to identify existing drugs already approved for use in humans which could be repurposed as COVID-19 therapeutics. Here we focus on antivirals directed against the SARS-CoV2 Mpro protease, which is required for virus replication. A structural similarity search showed that the Hepatitis C virus (HCV) NS3/4A protease has a striking three-dimensional structural similarity to the SARS-CoV2 Mpro protease, particularly in the arrangement of key active site residues. We used virtual docking predictions to assess the hypothesis that existing drugs already approved for human use or clinical testing that are directed at the HCV NS3/4A protease might fit well into the active-site cleft of the SARS-CoV2 protease (Mpro). AutoDock docking scores for 12 HCV protease inhibitors and 9 HIV-1 protease inhibitors were determined and compared to the docking scores for an \u03b1-ketoamide inhibitor of Mpro, which has recently been shown to inhibit SARS-CoV2 virus replication in cell culture. We identified eight HCV protease inhibitors that bound to the Mpro active site with higher docking scores than the \u03b1-ketoamide inhibitor, suggesting that these protease inhibitors may effectively bind to the Mpro active site. These results provide the rationale for us to test the identified HCV protease inhibitors as inhibitors of the SARS-CoV2 protease, and as inhibitors of SARS-CoV2 virus replication. Subsequently these repurposed drugs could be evaluated as COVID-19 therapeutics.", "qid": 3, "docid": "vvf3ei6v", "rank": 25, "score": 9.719300270080566}, {"content": "Title: Challenges in Dengue Vaccines Development: Pre-existing Infections and Cross-Reactivity Content: Dengue is one of the most frequently transmitted mosquito-borne diseases in the world, which creates a significant public health concern globally, especially in tropical and subtropical countries. It is estimated that more than 390 million people are infected with dengue virus each year and around 96 million develop clinical pathologies. Dengue infections are not only a health problem but also a substantial economic burden. To date, there are no effective antiviral therapies and there is only one licensed dengue vaccine that only demonstrated protection in the seropositive (Immune), naturally infected with dengue, but not dengue seronegative (Na\u00efve) vaccines. In this review, we address several immune components and their interplay with the dengue virus. Additionally, we summarize the literature pertaining to current dengue vaccine development and advances. Moreover, we review some of the factors affecting vaccine responses, such as the pre-vaccination environment, and provide an overview of the significant challenges that face the development of an efficient/protective dengue vaccine including the presence of multiple serotypes, antibody-dependent enhancement (ADE), as well as cross-reactivity with other flaviviruses. Finally, we discuss targeting T follicular helper cells (Tfh), a significant cell population that is essential for the production of high-affinity antibodies, which might be one of the elements needed to be specifically targeted to enhance vaccine precision to dengue regardless of dengue serostatus.", "qid": 3, "docid": "brb6pfte", "rank": 26, "score": 9.602999687194824}, {"content": "Title: COVID-19: Immunology and treatment options Content: The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.", "qid": 3, "docid": "528p64iu", "rank": 27, "score": 9.588500022888184}, {"content": "Title: COVID-19: Immunology and treatment options Content: Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.", "qid": 3, "docid": "r7ahl9gd", "rank": 28, "score": 9.588499069213867}, {"content": "Title: Herd immunity or suppression strategy to combat COVID-19. Content: Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called \"herd immunity\" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden.Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants).In the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state Taiwan has made the best out of the pandemic situation whereas Sweden failed completely.", "qid": 3, "docid": "8e1fkafa", "rank": 29, "score": 9.522500038146973}, {"content": "Title: Herd immunity or suppression strategy to combat COVID-19 Content: Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called \"herd immunity\" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden.Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants).In the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state Taiwan has made the best out of the pandemic situation whereas Sweden failed completely.", "qid": 3, "docid": "j7dmxpaf", "rank": 30, "score": 9.522499084472656}, {"content": "Title: Immunodominant viral peptides as determinants of cross-reactivity in the immune system \u2013 Can we develop wide spectrum viral vaccines? Content: Summary When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular \u201cviral patterns\u201d seems to be important steps towards the development of wide spectrum viral vaccines.", "qid": 3, "docid": "ae2x2wpg", "rank": 31, "score": 9.51200008392334}, {"content": "Title: SARS\u2010COV\u20102 and infectivity: Possible increase in infectivity associated to integrin motif expression Content: SARS-COV2 represents the causal agent of a potentially fatal disease (COVID-19) that is actually of great global public health concern. SARS-COV2 has diffused throughout the world surprisingly fast demonstrating a far greater infectivity than previously known human coronaviruses and it is also responsible for an unusual high variety of symptoms in affected patients. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "nfvbog77", "rank": 32, "score": 9.468700408935547}, {"content": "Title: The kidney in COVID-19: protagonist or figurant? Content: The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as \"at high risk\" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.", "qid": 3, "docid": "h9v5jqfc", "rank": 33, "score": 9.447699546813965}, {"content": "Title: Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic. Content: Background: COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, with no relation between the number of cases and mortality, suggesting the involvement of the populational genetic constitution and previous cross-reactive immune contacts in the individuals' disease outcome. Methods: A clustering approach was conducted to investigate the involvement of human MHC alleles with individuals' outcomes. HLA frequencies from affected countries were used to fuel the Hierarchical Clusterization Analysis. The formed groups were compared regarding their death rates. To prospect the T cell targets in SARS-CoV-2, and by consequence, the epitopes that are conferring cross-protection in the current pandemic, we modeled 3D structures of HLA-A*02:01 presenting immunogenic epitopes from SAR-CoV-1, recovered from Immune Epitope Database. These pMHC structures were also compared with models containing the corresponding SARS-CoV-2 epitope, with alphacoronavirus sequences, and with a panel of immunogenic pMHC structures contained in CrossTope. Findings: The combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLADRB1*04 allowed the clustering of affected countries presenting similar death rates, based only on their allele frequencies. SARS-CoV HLA-A*02:01 epitopes were structurally investigated. It reveals molecular conservation between SARS-CoV-1 and SARS-CoV-2 peptides, enabling the use of formerly SARS-CoV-1 experimental epitopes to inspect actual targets that are conferring cross-protection. Alpha-CoVs and, impressively, viruses involved in human infections share fingerprints of immunogenicity with SARS-CoV peptides. Interpretation: Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development. Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support", "qid": 3, "docid": "in48pd8t", "rank": 34, "score": 9.431500434875488}, {"content": "Title: A dissection of SARS-CoV2 with clinical implications (Review) Content: We are being confronted with the most consequential pandemic since the Spanish flu of 1918-1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS-CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso-pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried-and-true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID-19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS-CoV2 and proposed antiviral drugs; iii) The combination of arginine-ascorbate.", "qid": 3, "docid": "feo0axgx", "rank": 35, "score": 9.424099922180176}, {"content": "Title: SARS - CoV-2: Reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Content: The novel coronavirus Covid-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against Covid-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics (\"Spanish flu\" 1918, \"Asian flu\" 1956 and \"the Hong Kong flu\" 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4 + memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4 + memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting \"lung crash\" until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the Covid-19 will occur.", "qid": 3, "docid": "342thf3o", "rank": 36, "score": 9.402000427246094}, {"content": "Title: SARS \u2013 CoV -2: reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Content: Abstract The novel coronavirus COVID-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against COVID-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics (\u201cSpanish flu\u201d 1918, \u201cAsian flu\u201d 1956 and \u201cthe Hong Kong flu\u201d 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4+ memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4+ memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting \u201clung crash\u201d until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the COVID-19 will occur.", "qid": 3, "docid": "jfe8neec", "rank": 37, "score": 9.401999473571777}, {"content": "Title: Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution? Content: PURPOSE: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. METHODS: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI. RESULTS: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain\u2013Barr\u00e9 syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma. CONCLUSION: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.", "qid": 3, "docid": "4e2j89uy", "rank": 38, "score": 9.389399528503418}, {"content": "Title: Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution? Content: PURPOSE: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. METHODS: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI. RESULTS: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines, which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain-Barr\u00e9 syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma. CONCLUSION: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.", "qid": 3, "docid": "p4nv2a66", "rank": 39, "score": 9.389398574829102}, {"content": "Title: Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates Content: The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.", "qid": 3, "docid": "wzv8n34v", "rank": 40, "score": 9.366000175476074}, {"content": "Title: Current Status of the COVID-19 Outbreak and Emerging Management through Pharmaceutical Therapeutic Strategy. Content: The latest SARS COV2 coronavirus contributes to a pandemic of millions of COVID-19. Because there is no defensive immunity in humans and a virus can overcome inborn immune reaction, it can propagate unhindered, mostly in tissues contaminated. No unique therapies for COVID-19 contaminated patients are available at this time. The insights learned from previous respiratory viral infection control have given guidance into COVID-19 therapy. Several complementary treatments have been tentatively introduced in hospital environments such as immune-modulators, antiviral, convalescent plasma transfusions and natural products. In COVID-19 patients, some of these therapies have provided substantial curative benefits. Moreover, numerous studies and clinical trials are being carried out in order to determine the efficacy of current pharmaceutical and natural products and establish possible therapeutic strategies for producing novel COVID-19 medicines. We summarized and defined the modes of mechanism, protection and efficacy on existing therapeutic strategies for diseases linked to COVID-19 infection.", "qid": 3, "docid": "kpdfkl4e", "rank": 41, "score": 9.356300354003906}, {"content": "Title: Chapter 36 SARS Content: Abstract Five years after the first severe acute respiratory syndrome (SARS) outbreak, several candidate SARS-coronavirus (CoV) vaccines are at various stages of preclinical and clinical development. Based on the observation that SARSCoV infection is efficiently controlled upon passive transfer of antibodies directed against the spike (S) protein of SARS-CoV, vaccines containing the S protein have been formulated. Animals immunized with inactivated whole virus vaccines or live-recombinant vaccines expressing the SARS-CoV S protein (e.g., using rabies virus, vesicular stomatitis virus, bovine parainfluenza virus type 3, adenovirus, or attenuated vaccinia virus MVA as a vector), as well as mice immunized with DNA vaccines expressing the S protein gene all developed neutralizing antibodies to SARS-CoV and were protected against SARS-CoV challenge. Although much effort has been focused on developing a SARS vaccine, the commercial viability of such a vaccine for SARS-CoV will ultimately depend on whether the virus re-emerges in the near future. This vaccine should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. Given the fact that in the previous outbreak mainly the elderly succumbed to the infection, special attention should be given to vaccines that are able to efficiently protect aged individuals.", "qid": 3, "docid": "87g7g5au", "rank": 42, "score": 9.341899871826172}, {"content": "Title: Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV Content: BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected &#8805;14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 \u00b1 1.6; 5.7 \u00b1 1.8 and 7.9 \u00b1 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.", "qid": 3, "docid": "ph6pxseu", "rank": 43, "score": 9.312700271606445}, {"content": "Title: Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human Coronaviruses SARS-CoV and MERS-CoV Content: BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected \u226514 days after symptoms onset, the accuracy of the assay is 100% (95% CI: 100-100) for the Spike antigen and 99.9% (95% CI:99.7-100) for NC. By logistic regression, we estimated that 50% of the patients have seroconverted at 5.7 \u00b1 1.6; 5.7 \u00b1 1.8 and 7.9 \u00b1 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100% with SARS-CoV1 NC. Twenty-nine of the 36 (80.5%) samples tested were positive by the commercial ELISA while 31/36 (86.1%) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.", "qid": 3, "docid": "vvz5spk7", "rank": 44, "score": 9.312699317932129}, {"content": "Title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Content: COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity.", "qid": 3, "docid": "7dw32xby", "rank": 45, "score": 9.227299690246582}, {"content": "Title: Fundamental principles of epidemic spread highlight the immediate need for large-scale serological surveys to assess the stage of the SARS-CoV-2 epidemic Content: The spread of a novel pathogenic infectious agent eliciting protective immunity is typically characterised by three distinct phases: (I) an initial phase of slow accumulation of new infections (often undetectable), (II) a second phase of rapid growth in cases of infection, disease and death, and (III) an eventual slow down of transmission due to the depletion of susceptible individuals, typically leading to the termination of the (first) epidemic wave. Before the implementation of control measures (e.g. social distancing, travel bans, etc) and under the assumption that infection elicits protective immunity, epidemiological theory indicates that the ongoing epidemic of SARS-CoV-2 will conform to this pattern. Here, we calibrate a susceptible-infected-recovered (SIR) model to data on cumulative reported SARS-CoV-2 associated deaths from the United Kingdom (UK) and Italy under the assumption that such deaths are well reported events that occur only in a vulnerable fraction of the population. We focus on model solutions which take into consideration previous estimates of critical epidemiological parameters such as the basic reproduction number (R0), probability of death in the vulnerable fraction of the population, infectious period and time from infection to death, with the intention of exploring the sensitivity of the system to the actual fraction of the population vulnerable to severe disease and death. Our simulations are in agreement with other studies that the current epidemic wave in the UK and Italy in the absence of interventions should have an approximate duration of 2-3 months, with numbers of deaths lagging behind in time relative to overall infections. Importantly, the results we present here suggest the ongoing epidemics in the UK and Italy started at least a month before the first reported death and have already led to the accumulation of significant levels of herd immunity in both countries. There is an inverse relationship between the proportion currently immune and the fraction of the population vulnerable to severe disease. This relationship can be used to determine how many people will require hospitalisation (and possibly die) in the coming weeks if we are able to accurately determine current levels of herd immunity. There is thus an urgent need for investment in technologies such as virus (or viral pseudotype) neutralization assays and other robust assays which provide reliable read-outs of protective immunity, and for the provision of open access to valuable data sources such as blood banks and paired samples of acute and convalescent sera from confirmed cases of SARS-CoV-2 to validate these. Urgent development and assessment of such tests should be followed by rapid implementation at scale to provide real-time data. These data will be critical to the proper assessment of the effects of social distancing and other measures currently being adopted to slow down the case incidence and for informing future policy direction.", "qid": 3, "docid": "n10abfvd", "rank": 46, "score": 9.2076997756958}, {"content": "Title: The modelling of COVID19 pathways sheds light on mechanisms, opportunities and on controversial interpretations of medical treatments. v2 Content: The new coronavirus (2019-nCoV or SARS-CoV2), inducing the current pandemic disease (COVID-19) and causing pneumoniae in humans, is dramatically increasing in epidemic scale since its first appearance in Wuhan, China, in December 2019. The first infection from epidemic coronaviruses in 2003 fostered the spread of an overwhelming amount of related scientific efforts. The manifold aspects that have been raised, as well as their redundancy offer precious information that has been underexploited and needs to be critically re-evaluated, appropriately used and offered to the whole community, from scientists, to medical doctors, stakeholders and common people. These efforts will favour a holistic view on the comprehension, prevention and development of strategies (pharmacological, clinical etc) as well as common intervention against the new coronavirus spreading. Here we describe a model that emerged from our analysis that was focused on the Renin Angiotensin System (RAS) and the possible routes linking it to the viral infection. because the infection is mediated by the viral receptor on human cell membranes Angiotensin Converting Enzyme (ACE2), which is a key component in RAS signalling. The model depicts the main pathways determining the disease and the molecular framework for its establishment, and can help to shed light on mechanisms involved in the infection. It promptly gives an answer to some of the controversial, and still open, issues concerning predisposing conditions and medical treatments that protect from or favour the severity of the disease (such as the use of ACE inhibitors or ARBs/sartans), or to the sex related biases in the affected population. The model highlights novel opportunities for further investigations, diagnosis and appropriate intervention to understand and fight COVID19.", "qid": 3, "docid": "bayj4dtg", "rank": 47, "score": 9.185099601745605}, {"content": "Title: Control of influenza virus infection by immunity to conserved viral features. Content: Influenza has circulated among humans for centuries and kills more people than many newly emerging diseases. The present methods for control of influenza are not adequate, especially for dealing with a pandemic. In the face of a rapidly spreading outbreak, a race to isolate the virus and prepare a vaccine would probably not succeed in time to avoid great losses. Thus, additional anti-infection strategies are needed. Broad cross-protection against widely divergent influenza A subtypes is readily achieved in animals by several means of immunization. How does cross-protection work in animals, and can we apply what we have learned about it to induce broad cross-protection in humans?", "qid": 3, "docid": "1s0jw2bd", "rank": 48, "score": 9.16819953918457}, {"content": "Title: A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate Content: The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.", "qid": 3, "docid": "zwsvlnwe", "rank": 49, "score": 9.161100387573242}, {"content": "Title: Serological differentiation between COVID-19 and SARS infections Content: In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "qid": 3, "docid": "9skvbk8m", "rank": 50, "score": 9.06779956817627}, {"content": "Title: T cells found in COVID-19 patients \u2018bode well\u2019 for long-term immunity Content: SARS-CoV-2, the virus that causes COVID-19, has been unclear Now, two studies reveal that infected people harbor T cells that target the virus\u2014and may help them recover Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses \u201cThis is encouraging data,\u201d says virologist Angela Rasmussen of Columbia University Although the studies don\u2019t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which \u201cbodes well for the development of long-term protective immunity,\u201d Rasmussen says The findings could also help researchers create better vaccines", "qid": 3, "docid": "88px7oq2", "rank": 51, "score": 9.050100326538086}, {"content": "Title: Ribosomal proteins as a possible tool for blocking SARS-COV 2 virus replication for a potential prospective treatment Content: Coronavirus disease (COVID-19) is caused by SARS-COV2 and has resulted in more than four million cases globally and the death cases exceeded 300,000. Normally, a range of surviving and propagating host factors must be employed for the completion of the infectious process including RPs. Viral protein biosynthesis involves the interaction of numerous RPs with viral mRNA, proteins which are necessary for viruses replication regulation and infection inside the host cells. Most of these interactions are crucial for virus activation and accumulation. However, only small percentage of these proteins is specifically responsible for host cells protection by triggering the immune pathway against virus. This research proposes RPs extracted from bacillus sp. and yeast as new forum for the advancement of antiviral therapy. Hitherto, antiviral therapy with RPs-involving viral infection has not been widely investigated as critical targets. Also, exploring antiviral strategy based on RPs could be a promising guide for more potential therapeutics.", "qid": 3, "docid": "auzknkbx", "rank": 52, "score": 9.042699813842773}, {"content": "Title: Ribosomal proteins as a possible tool for blocking SARS-COV 2 virus replication for a potential prospective treatment. Content: Coronavirus disease (COVID-19) is caused by SARS-COV2 and has resulted in more than four million cases globally and the death cases exceeded 300,000. Normally, a range of surviving and propagating host factors must be employed for the completion of the infectious process including RPs. Viral protein biosynthesis involves the interaction of numerous RPs with viral mRNA, proteins which are necessary for viruses replication regulation and infection inside the host cells. Most of these interactions are crucial for virus activation and accumulation. However, only small percentage of these proteins is specifically responsible for host cells protection by triggering the immune pathway against virus. This research proposes RPs extracted from bacillus sp. and yeast as new forum for the advancement of antiviral therapy. Hitherto, antiviral therapy with RPs-involving viral infection has not been widely investigated as critical targets. Also, exploring antiviral strategy based on RPs could be a promising guide for more potential therapeutics.", "qid": 3, "docid": "uwmk2a5b", "rank": 53, "score": 9.042698860168457}, {"content": "Title: Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities Content: Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The degree of similarity is such that perhaps prior exposure to one virus could confer partial immunity to another. Indeed, data suggests a considerable amount of cross-reactivity and recognition by the hosts immune response between different coronavirus infections. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of global deaths, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of coronavirus infections, perhaps suggesting buildup of acquired immunity to the causative SARS-CoV-2 that underlies COVID-19. This article hypothesizes that a causative factor underlying such low morbidity in these regions is perhaps (at least in part) due to acquired immunity from multiple rounds of coronavirus infections and discusses the mechanisms and recent evidence to support such assertions. Further investigations of such phenomenon would allow us to examine strategies to confer protective immunity, perhaps aiding vaccine development.", "qid": 3, "docid": "01q4pu9k", "rank": 54, "score": 9.026200294494629}, {"content": "Title: Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal Betacoronaviruses Content: In order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other Betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.", "qid": 3, "docid": "yigj0u3n", "rank": 55, "score": 9.016300201416016}, {"content": "Title: Conserved epitopes of influenza A virus inducing protective immunity and their prospects for universal vaccine development Content: Influenza A viruses belong to the best studied viruses, however no effective prevention against influenza infection has been developed. The emerging of still new escape variants of influenza A viruses causing epidemics and periodic worldwide pandemics represents a threat for human population. Therefore, current, hot task of influenza virus research is to look for a way how to get us closer to a universal vaccine. Combination of chosen conserved antigens inducing cross-protective antibody response with epitopes activating also cross-protective cytotoxic T-cells would offer an attractive strategy for improving protection against drift variants of seasonal influenza viruses and reduces the impact of future pandemic strains. Antigenically conserved fusion-active subunit of hemagglutinin (HA2 gp) and ectodomain of matrix protein 2 (eM2) are promising candidates for preparation of broadly protective HA2- or eM2-based vaccine that may aid in pandemic preparedness. Overall protective effect could be achieved by contribution of epitopes recognized by cytotoxic T-lymphocytes (CTL) that have been studied extensively to reach much broader control of influenza infection. In this review we present the state-of-art in this field. We describe known adaptive immune mechanisms mediated by influenza specific B- and T-cells involved in the anti-influenza immune defense together with the contribution of innate immunity. We discuss the mechanisms of neutralization of influenza infection mediated by antibodies, the role of CTL in viral elimination and new approaches to develop epitope based vaccine inducing cross-protective influenza virus-specific immune response.", "qid": 3, "docid": "dc7fn26s", "rank": 56, "score": 8.988200187683105}, {"content": "Title: Elevated expression of ACE2 in tumor-adjacent normal tissues of cancer patients Content: The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression patterns of ACE2, the receptor through which SARX-CoV2 enters human cells, and found that ACE2 mRNA levels are elevated in tumor-adjacent normal tissues of cancer patients, including in normal-adjacent lung tissues of lung cancer patients. These observations raise the possibility that the elevated COVID-19 risk of cancer patients may not be limited to those undergoing immune-suppressing treatment.", "qid": 3, "docid": "p15bdmo2", "rank": 57, "score": 8.93649959564209}, {"content": "Title: Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity Content: As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated.", "qid": 3, "docid": "bah2ege0", "rank": 58, "score": 8.90820026397705}, {"content": "Title: Serological differentiation between COVID-19 and SARS infections. Content: In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "qid": 3, "docid": "0jl6qu0i", "rank": 59, "score": 8.87090015411377}, {"content": "Title: Serological differentiation between COVID-19 and SARS infections Content: In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "qid": 3, "docid": "0yj3xp9s", "rank": 60, "score": 8.870899200439453}, {"content": "Title: Vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of SARS-like coronavirus generates humoral and cellular immune responses Content: Abstract Continuous efforts have been made to develop a prophylactic vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, two recombinant baculoviruses, vAc-N and vAc-S, were constructed, which contained the mammalian-cell activate promoter element, human elongation factor 1\u03b1-subunit (EF-1\u03b1), the human cytomegalovirus (CMV) immediate-early promoter, and the nucleocapsid (N) or spike (S) gene of bat SARS-like CoV (SL-CoV) under the control of the CMV promoter. Mice were subcutaneously and intraperitoneally injected with recombinant baculovirus, and both humoral and cellular immune responses were induced in the vaccinated groups. The secretion level of IFN-\u03b3 was much higher than that of IL-4 in vAc-N or vAc-S immunized groups, suggesting a strong Th1 bias towards cellular immune responses. Additionally, a marked increase of CD4 T cell immune responses and high levels of anti-SARS-CoV humoral responses were also detected in the vAc-N or vAc-S immunized groups. In contrast, there were significantly weaker cellular immune responses, as well as less antibody production than in the control groups. Our data demonstrates that the recombinant baculovirus can serve as an effective vaccine strategy. In addition, because effective SARS vaccines should act to not only prevent the reemergence of SARS-CoV, but also to provide cross-protection against SL-CoV, findings in this study may have implications for developing such cross-protective vaccines.", "qid": 3, "docid": "9u2tl1d5", "rank": 61, "score": 8.821999549865723}, {"content": "Title: Vaccines Content: Vaccines are predominantly used for prevention; that means they should establish a protection in immunized people or animals which will protect them from a possible infection and the subsequent illness when they come into contact with the respective pathogens. Fundamentally, there are two kinds of immunization: active and passive. The latter is based on the administration of immunoglobulin preparations that can neutralize a specific virus. Therefore, passive vaccination is applied only in special cases, such as when the person to be protected recently had verifiable contact with a specific virus (postexposure prophylaxis), or if the risk of exposure to pathogens cannot be ruled out in the following weeks and an active vaccination is not possible, as in short-term planned trips to Third World countries (exposure prophylaxis). An example is the administration of antibodies specific for hepatitis B virus in cases of contamination with blood from people who have an acute or chronically persistent infection with this virus, and thus have high concentrations of infectious particles in the blood. Such accidents occur primarily in medical personnel by needlestick injury (10.1007/978-3-642-20718-1_19). In certain cases, the administration is performed in combination with an active vaccination (active\u2013passive immunization). Specific immunoglobulin preparations are also administered when people have been bitten by animals that may be infected with the rabies virus (10.1007/978-3-642-20718-1_15). In the case of early application (together with an active vaccination), the antibodies can neutralize the virus, and impede its spread in the body. Since the time between contact with the virus and its spread in the organism is often very short, passive immunization is limited to a period shortly before or after exposure to the infective agent (usually within 4 days). Therefore, it is reserved for cases in which the contact with the potential pathogen is well documented and the type of infection is known, and when an appropriate immunoglobulin preparation is available. The protection afforded by antibody preparations lasts just a few weeks, as immunoglobulins are rapidly degraded in the organism. Therefore, postexposure administration of active vaccines is increasingly preferred, e.g. in the context of outbreak-control vaccination. In veterinary medicine, passive immunization is employed occasionally in young animals which were born in a flock with high infection pressure. This approach is applied, for example, in kennels when infections occur with canine parvovirus (10.1007/978-3-642-20718-1_20). However, its value is controversial, as the immunoglobulins administered hinder the more advantageous active immunization.", "qid": 3, "docid": "afzjx2ci", "rank": 62, "score": 8.805700302124023}, {"content": "Title: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease Content: The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.", "qid": 3, "docid": "yzffm05r", "rank": 63, "score": 8.783499717712402}, {"content": "Title: SARS-CoV-2 Antibody Testing \u2013 Questions to be asked Content: ABSTRACT SARS-CoV-2 infection and development of COVID-19 disease presents a major healthcare challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against the SARS-CoV-2 virus presents a major cornerstone in handling the pandemic. Currently there is an increase in demand of antibody testing and a large number of tests are already marketed or in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity; the diagnostic value of antibodies of different isotypes, the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues based on the currently available datasets in this rapidly moving field.", "qid": 3, "docid": "tveeq4fj", "rank": 64, "score": 8.706700325012207}, {"content": "Title: Systemic Immunobiological, Immunosuppressant and Oncologic Agents for the Treatment of Dermatologic Diseases during the SARS\u2010Cov\u20102 (COVID19) Pandemic Emergency: a Quick Review for a Quick Consultation Content: The Precision Medicine Era has helped to better manage patients with immunological and oncological disease, improving the quality of life of this class of patients. Regarding the management of these patients and positivity to SARS\u2010Cov2, currently, limited data is available and information is evolving. In this quick review we have analyzed the mechanisms of action and related infective risk of drugs used for the treatment of immune\u2010mediated and oncologic skin conditions during the daily clinical practice. In general immunosuppressant and antineoplastic agents for dermatologic treatments do not require suspension and do not require special measures, if not those commonly observed. In the case of a COVID19 patient with complication (such as pneumonia, respiratory failure), treatment suspension should always be considered after taking into account the general condition of the patient, the risk\u2010benefit ratio and the pathophysiology of COVID19 infection. The COVID19 emergency pandemic does not imply an under\u2010treatment of existing skin conditions, which together with the SARS\u2010Cov2 infection may jeopardize the patient's life. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "69kkffjo", "rank": 65, "score": 8.703200340270996}, {"content": "Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 3, "docid": "rs79r7kc", "rank": 66, "score": 8.695199966430664}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 3, "docid": "rsz7ch2a", "rank": 67, "score": 8.695199012756348}, {"content": "Title: Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial Content: BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). Participants: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit \u2013ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 \u22652) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqu\u00e9s de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqu\u00e9s de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Inclusion criteria: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. Exclusion criteria: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: 1. Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months. 2. Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months. MAIN OUTCOMES: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see \u201cDiagnosis of SARS CoV2 infection\u201d below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms; number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 \u22652) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products \u201cAEMPS\u201d) and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).", "qid": 3, "docid": "6ngxo8ff", "rank": 68, "score": 8.68809986114502}, {"content": "Title: Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial Content: BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit -ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 &#8805;2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqu\u00e9s de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqu\u00e9s de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. INCLUSION CRITERIA: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. EXCLUSION CRITERIA: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: Two groups will be analyzed with a 1: 1 randomization rate. 1)Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months.2)Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months MAIN OUTCOMES: The primary outcome of this study will be to evaluate: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see \"Diagnosis of SARS CoV2 infection\" below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms;number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 &#8805;2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products \"AEMPS\") and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).", "qid": 3, "docid": "rxvxf34z", "rank": 69, "score": 8.688098907470703}, {"content": "Title: Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus Content: The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100,000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an &#945;-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.", "qid": 3, "docid": "agmfh8h9", "rank": 70, "score": 8.684399604797363}, {"content": "Title: Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus. Content: The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an \u03b1-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.", "qid": 3, "docid": "yuxb2jz9", "rank": 71, "score": 8.684398651123047}, {"content": "Title: Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses Content: Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-\u03b3-dependent and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.", "qid": 3, "docid": "fj2rjmop", "rank": 72, "score": 8.679499626159668}, {"content": "Title: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2 Content: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9\u201317 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "qid": 3, "docid": "8i1u1a9t", "rank": 73, "score": 8.638699531555176}, {"content": "Title: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2 Content: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "qid": 3, "docid": "buwz6lu3", "rank": 74, "score": 8.63869857788086}, {"content": "Title: Optimized pseudotyping conditions for the SARS-COV2 Spike glycoprotein Content: The SARS-COV2 Spike glycoprotein is solely responsible for binding to the host cell receptor and facilitating fusion between the viral and host membranes. The ability to generate viral particles pseudotyped with SARS-COV2 Spike is useful for many types of studies, such as characterization of neutralizing antibodies or development of fusion-inhibiting small molecules. Here we characterized the use of a codon-optimized SARS-COV2 Spike glycoprotein for the generation of pseudotyped HIV-1, MLV, and VSV particles. The full-length Spike protein functioned inefficiently with all three systems but was enhanced over 10-fold by deleting the last 19 amino acids of the cytoplasmic tail of Spike. Infection of 293FT target cells was only possible if the cells were engineered to stably express the human ACE-2 receptor, but stably introducing an additional copy of this receptor did not further enhance susceptibility. Stable introduction of the Spike activating protease TMPRSS2 further enhanced susceptibility to infection by 5-10 fold. Substitution of the signal peptide of the Spike protein with an optimal signal peptide did not enhance or reduce infectious particle production. However, modification of a single amino acid in the furin cleavage site of Spike (R682Q) enhanced infectious particle production another 10-fold. With all enhancing elements combined, the titer of pseudotyped particles reached almost 106 infectious particles/ml. Finally, HIV-1 particles pseudotyped with SARS-COV2 Spike was successfully used to detect neutralizing antibodies in plasma from COVID-19 patients, but not plasma from uninfected individuals. Importance When working with pathogenic viruses, it is useful to have rapid quantitative tests for viral infectivity that can be performed without strict biocontainment restrictions. A common way of accomplishing this is to generate viral pseudoparticles that contain the surface glycoprotein from the pathogenic virus incorporated into a replication-defective viral particle that contains a sensitive reporter system. These pseudoparticles enter cells using the glycoprotein from the pathogenic virus leading to a readout for infection. Conditions that block entry of the pathogenic virus, such as neutralizing antibodies, will also block entry of the viral pseudoparticles. However, viral glycoproteins often are not readily suited for generating pseudoparticles. Here we describe a series of modifications that result in the production of relatively high titer SARS-COV2 pseudoparticles that are suitable for detection of neutralizing antibodies from COVID-19 patients.", "qid": 3, "docid": "4t6f7wul", "rank": 75, "score": 8.635100364685059}, {"content": "Title: Emerging Trends in COVID-19 Treatment: Learning from Inflammatory Conditions Associated with Cellular Therapies Content: Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.", "qid": 3, "docid": "f7wk75cm", "rank": 76, "score": 8.62720012664795}, {"content": "Title: Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies Content: Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.", "qid": 3, "docid": "sjx512z2", "rank": 77, "score": 8.627199172973633}, {"content": "Title: NK cells: A double edge sword against SARS-CoV-2 Content: Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).", "qid": 3, "docid": "acn0mvax", "rank": 78, "score": 8.597800254821777}, {"content": "Title: Protective Adaptive Immunity Against Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2) and Implications for Vaccines Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging human coronavirus responsible for coronavirus disease 2019 (COVID-19), a predominantly respiratory disease that has become a global pandemic. Millions of people worldwide are suffering from COVID-19, and hundreds of thousands of those infected have died. Nevertheless, many more people who have been infected with SARS-CoV-2 are asymptomatic or suffer a mild disease characterized by dry cough and mild fever. This new pandemic poses a threat to public health on a global scale, and an intervention to prevent continued spread of SARS-CoV-2 virus is of the utmost importance. To assess preventive and therapeutic strategies, it is imperative to understand the pathogenesis and immune response against SARS-CoV-2. In this review, we concentrate on the protective adaptive immune response elicited by this novel coronavirus as well as requirements for a successful vaccine inducing optimal protection.", "qid": 3, "docid": "bcqdm2b1", "rank": 79, "score": 8.597000122070312}, {"content": "Title: A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses Content: Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.", "qid": 3, "docid": "bk6sawaf", "rank": 80, "score": 8.596099853515625}, {"content": "Title: The Association between Obesity and Poor Outcome after COVID-19 Indicates a Potential Therapeutic Role for Montelukast Content: It is widely believed that infection with the SARS-CoV2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1\u03b2, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense \u2018cytokine storm\u2019 is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1\u03b2 and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus\u2019s main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.", "qid": 3, "docid": "6kz0iws6", "rank": 81, "score": 8.593099594116211}, {"content": "Title: Antibody Profiling and Prevalence in the US population during the SARS-CoV2 Pandemic Content: ABSTRACT Background: Antibody diagnostics play an important role in disease detection and can potentially aid in monitoring of the immune responses to see if an individual has developed immunity. Developing high throughput diagnostics which does not involve handling of infectious material becomes imperative in the case of pandemics such as the recent outbreak of SARS-CoV2. Methods: A protein microarray technology was used to detect the plurality of antibody response to four novel antigens namely S1 glycoprotein, Receptor binding domain (RBD), S2 glycoprotein and Nucleoprotein of the novel coronavirus named SARS-CoV2 using serum samples. A DBS card was additionally used to compare its performance with a venipuncture-based serum separator tube (SST) draw. Results: The three main subclasses of antibodies IgM, IgA and IgG were analyzed to see the variations in immune responses in the affected population and compared to their microbial RT-PCR based NP swab results. The clinical sensitivity and specificity were determined to be 98.1% and 98.6%. In the matrix comparison study, which would enable patients to test without risk of transmitting the virus, DBS matched with higher than 98% accuracy to a venipuncture-based SST collection. Conclusion: Multiplex testing enables higher sensitivity and specificity which is essential while establishing exposure on a population scale. This flexible platform along with a discrete collection methodology would be crucial and broadly useful to scale up testing in current and future pandemics. Minimum sample volume that can be collected using DBS cards can be processed in this multiplex pillar plate format enabling the capacity to provide the reliability of high throughput analyzers while having the ease of collection similar to rapid tests. Keywords: COVID19, SARS-CoV2, Antibody, Multiplex, serology, biomarker, immune modulation, prevalence, high sensitivity, high specificity, Dried blood spot, pandemic, venipuncture", "qid": 3, "docid": "8uu10t4p", "rank": 82, "score": 8.591899871826172}, {"content": "Title: Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes. Content: Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.", "qid": 3, "docid": "hhq0wmgg", "rank": 83, "score": 8.57509994506836}, {"content": "Title: A case report of possible novel coronavirus 2019 reinfection Content: Since December 2019, COVID-19, the clinical syndrome associated with SARS-CoV-2 infection, has infected more than 6.2 million people and brought the function of the global community to a halt. As the number of patients recovered from COVID-19 rises and the world transitions toward reopening, the question of acquired immunity versus the possibility of reinfection are critical to anticipating future viral spread. Here, we present a case of a patient previously recovered from COVID-19 who re-presents with new respiratory, radiographical, laboratory, and RT-PCR findings concerning for re-infection. We review this case in the context of the evolving discussion and theories surrounding dynamic RT-PCR results, prolonged viral shedding, and the possibility of developed immunity.", "qid": 3, "docid": "aed6psww", "rank": 84, "score": 8.571499824523926}, {"content": "Title: Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane? Content: BACKGROUND AND AIMS: People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS: We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS: Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS: Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.", "qid": 3, "docid": "q1ai1ilp", "rank": 85, "score": 8.568599700927734}, {"content": "Title: Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane? Content: BACKGROUND AND AIMS People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.", "qid": 3, "docid": "y3489g72", "rank": 86, "score": 8.568598747253418}, {"content": "Title: Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers Content: The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.", "qid": 3, "docid": "3a7nvzfx", "rank": 87, "score": 8.568400382995605}, {"content": "Title: Fighting COVID-19. Content: The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.", "qid": 3, "docid": "h2xn9n20", "rank": 88, "score": 8.501399993896484}, {"content": "Title: Fighting COVID-19 Content: The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.", "qid": 3, "docid": "yzb8pouz", "rank": 89, "score": 8.501399040222168}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection. Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 3, "docid": "5rc9x979", "rank": 90, "score": 8.498299598693848}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 3, "docid": "vt56yqel", "rank": 91, "score": 8.498298645019531}, {"content": "Title: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection Content: [Image: see text] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is \u223c2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.", "qid": 3, "docid": "44tjfttb", "rank": 92, "score": 8.491900444030762}, {"content": "Title: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is \u00e2\u0088\u00bc2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.", "qid": 3, "docid": "7ns5omnu", "rank": 93, "score": 8.491899490356445}, {"content": "Title: Recombinant tandem epitope vaccination provides cross protection against Actinobacillus pleuropneumoniae challenge in mice Content: Actinobacillus pleuropneumoniae (A. pleuropneumoniae/APP) is the pathogen that causes porcine contagious pleuropneumonia. Actinobacillus pleuropneumoniae is divided into 18 serovars, and the cross protection efficacy of epitopes is debatable, which has resulted in the slow development of a vaccine. Consequently, epitope-based vaccines conferring Actinobacillus pleuropneumoniae cross protection have rarely been reported. In this study, B cell epitopes in the head domain of trimeric autotransporter adhesin were predicted, and 6 epitopes were selected. Then, the predicted epitopes (Ba1, Bb5, C1, PH1 and PH2) were connected by linkers to construct a recombinant tandem antigen (rta) gene. The RTA protein encoded by the recombinant rta gene was expressed, and finally the ICR mice were immunized with the RTA protein with or without inactivated Actinobacillus pleuropneumoniae (serovars 1 and 5b) and challenged with Actinobacillus pleuropneumoniae to evaluate the protective effect of the epitope-based vaccine and combined vaccine. The mice in the RTA-immunized group and RTA plus inactivated Actinobacillus pleuropneumoniae vaccine group had a significant improvement in clinical symptoms and a higher level of antibody in the serum than those in the control group. The RTA immune group had a 40% survival rate after Actinobacillus pleuropneumoniae infection, whereas the combination of RTA and inactivated Actinobacillus pleuropneumoniae produced very strong cross immune protection in mice, at least 50% (RTA IB1 + C5) and at most 100% (RTA IB5 + C1), whereas no cross immunoprotection was found in the solo Actinobacillus pleuropneumoniae immune group. Overall, the combination of the RTA protein and inactivated bacteria significantly enhanced the cross protection effects. This implies that RTA protein in combination with a suitable inactivated Actinobacillus pleuropneumoniae strain could be a candidate vaccine for porcine contagious pleuropneumonia.", "qid": 3, "docid": "9emycw07", "rank": 94, "score": 8.488699913024902}, {"content": "Title: Cross-protective immune responses elicited by a Korean variant of infectious bronchitis virus. Content: Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide. IBVs continuously evolve by developing mutations in antigenic sites; therefore, an IBV vaccine that provides broad cross-protection can be a highly relevant and practical method in IBV control strategies. Although some IBV vaccine strains are known to provide protection against multiple IBV serotypes, in general commercially available IBV vaccine strains provide protection against antigenically related viruses but not distinct heterologous viruses. In the present study we characterized the Korean variant IBV K40/09 strain with regard to its immunogenicity and protective efficacy against seven currently circulating IBV serotypes. Three-week-old specific-pathogen-free chickens were intraocularly immunized with the IBV K40/09 strain at 10(3.5) 50% egg infective dose (EID50). Three weeks after immunization all the birds were challenged with seven different strains at 10(4.5) EID50. Chickens immunized with the IBV K40/09 strain showed significantly high levels of protection against all challenge viruses at the trachea and kidney levels. Our results suggest that IBV K40/09 could be useful to ensure IBV vaccine effectiveness owing to its cross-protective ability. Therefore, the IBV K40/09 strain merits consideration as a vaccine candidate to prevent infection as well as the spread of new IBV strains and many IBV variants that have been reported worldwide.", "qid": 3, "docid": "8hon8anb", "rank": 95, "score": 8.464400291442871}, {"content": "Title: Does the Bacillus Calmette\u2013Gu\u00e9rin vaccine provide protection from COVID-19? Content: OBJECTIVE: The novel coronavirus pandemic is ravaging throughout the world. It has infected more than 1.2 million people and killed more than 64,000. Frantic research is underway to find prevention and cure. Of late, Bacillus Calmette\u2013Gu\u00e9rin (BCG) has been speculated as a possible protection from COVID-19. We sought to investigate the evidence behind the claim. MATERIAL AND METHODS: Data were collected regarding the total number of COVID-19 cases per million and total number of COVID-19 deaths per million in various countries. The BCG vaccination policies of these countries were also obtained. RESULTS: It was seen that the countries with no universal BCG policy had a mean 1272.9 (median 795) cases per million and 80.7 deaths (median 18) per million population. On the contrary, the countries with a universal BCG vaccination policy had a mean 131.2 (median 40) cases per million and 4 deaths (median 1) per population. The difference is highly significant (P < 0.001). CONCLUSION: The data strongly support the hypothesis that BCG may offer protection from COVID-19. Heterologous protection offered by BCG through production of trained immunity, epigenetic reprogramming of monocytes, non-specific activation of NK cells, and increase of pro-inflammatory cytokines (particularly, tumor necrosis factor [TNF]-alpha and interleukin 1 beta) production may be the mechanism behind its cross- protection against the novel coronavirus.", "qid": 3, "docid": "1waejlwb", "rank": 96, "score": 8.455900192260742}, {"content": "Title: Protection against homo and hetero-subtypic in\ufb02uenza A virus by optimized M2e DNA vaccine Content: Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.", "qid": 3, "docid": "ekxq4l9a", "rank": 97, "score": 8.453700065612793}, {"content": "Title: Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals Content: The current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs. Summary Serum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.", "qid": 3, "docid": "7jwhypgs", "rank": 98, "score": 8.449999809265137}, {"content": "Title: Protocol for a multicentre study of nosocomial SARS-CoV2 transmission The NOSO-COR Project Content: Introduction: The newly identified SARS-CoV2 can cause serious acute respiratory infections such as pneumonia with a mortality rate of approximately 2% to 4%. In the current context of high incidence rates of SARS-CoV2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to study and document suspected or confirmed cases of nosocomial SARS-CoV2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. Methods and analysis: This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients, care givers and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case-report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV2 by RT-PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV2 infections relative to all patients with syndromes suggestive of 2019-nCoV infection will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. Ethics and dissemination: This study was approved by the clinical research and committee of Ile de France V on March 8, 2020. Registration details: The trial was registered in ClinicalTrials (NCT04290780).", "qid": 3, "docid": "zzp6cj76", "rank": 99, "score": 8.440299987792969}, {"content": "Title: Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - Lung axis hypothesis Content: Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPs (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage.", "qid": 3, "docid": "rd4iqz1o", "rank": 100, "score": 8.43910026550293}]}
{"query": "what causes death from Covid-19?", "hits": [{"content": "Title: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales. Content: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 4, "docid": "2jttlljm", "rank": 1, "score": 8.748900413513184}, {"content": "Title: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales Content: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 4, "docid": "qg4xl5w8", "rank": 2, "score": 8.748899459838867}, {"content": "Title: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Content: Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "qid": 4, "docid": "ev9p2apu", "rank": 3, "score": 7.940199851989746}, {"content": "Title: Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal. Content: INTRODUCTION Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS Despite the inherent uncertainty, it is safe to assume an observed excess mortality of 2400 to 4000 deaths. Excess mortality was associated with older age groups (over age 65). DISCUSSION The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION The excess mortality occurred between March 1 and April 22 was 3 to 5 fold higher than what can be explained by the official COVID-19 deaths.", "qid": 4, "docid": "1v5o4as8", "rank": 4, "score": 7.579899787902832}, {"content": "Title: Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal Content: INTRODUCTION: Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS: Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS: An excess mortality of 2400 to 4000 deaths was observed. Excess mortality was associated with older age groups (over age 65) [corrected]. DISCUSSION: The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION: Despite the inherent uncertainty, the excess mortality occurred between March 1 and April 22 could be 3.5- to 5-fold higher than what can be explained by the official COVID-19 deaths [corrected].", "qid": 4, "docid": "jibgnn78", "rank": 5, "score": 7.579898834228516}, {"content": "Title: What we know about 2019-nCoV in Iran in the early stage? Content: On 10 January 2020, a new coronavirus causing a pneumonia outbreak spread rapidly in all of the World. On 19 February 2020, the first official announcement of death from 2019-Nov was made in Iran. As of 7 March 2020, there were 101,927 confirmed cases of Covid-19 infection, including 3486 deaths, reported in the World. In the eastern and Mediterranean region Iran with 4747 confirmed cases of Covid-19 infection and 124 deaths, is in the critical stage. Therefore, there is a matter of urgency combating this new virus and stopping the epidemic. Here, we focus on symptoms and the development of fast diagnosis methods, as well as potential management to prevent or treat the Covid-19 infection.", "qid": 4, "docid": "1z0kn95v", "rank": 6, "score": 7.550000190734863}, {"content": "Title: Trends in excess cancer and cardiovascular deaths in Scotland during the COVID-19 pandemic 30 December 2019 to 20 April 2020 Content: Understanding the trends in causes of death for different diseases during the current COVID-19 pandemic is important to determine whether there are excess deaths beyond what is normally expected. Using the most recent report from National Records Scotland (NRS) on 29 April 2020, we examined the percentage difference in crude numbers of deaths in 2020 compared to the average for 2015-2019 by week of death within calendar year. To determine if trends were similar, suggesting underreporting/underdiagnosed COVID-19 related deaths, we also looked at the trends in % differences for cardiovascular disease deaths. From the first 17 weeks' of data, we found a peak in excess deaths between weeks 14 of 2020, about four weeks after the first case in Scotland was detected on 1 March 2020-- but by week 17 these excesses had diminished around the time lockdown in the UK began. Similar observations were seen for cardiovascular disease-related deaths. These observations suggest that the short-term increase in excess cancer and cardiovascular deaths might be associated with undetected/unconfirmed deaths related to COVID-19. Both of these conditions make patients more susceptible to infection and lack of widespread access to testing for COVID-19 are likely to have resulted in under-estimation of COVID-19 mortality. These data further suggest that the cumulative toll of COVID-19 on mortality is likely undercounted. More detailed analysis is needed to determine if these excesses were directly or indirectly related to COVID-19. Disease specific mortality will need constant monitoring for the foreseeable future as changes occur in increasing capacity and access to testing, reporting criteria, changes to health services and different measures are implemented to control the spread of the COVID-19. Multidisciplinary, multi-institutional, national and international collaborations for complementary and population specific data analysis is required to respond and mitigate adverse effects of the COVID-19 pandemic and to inform planning for future pandemics.", "qid": 4, "docid": "223v2obv", "rank": 7, "score": 7.4670000076293945}, {"content": "Title: EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN. Content: Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.", "qid": 4, "docid": "0o3wjvpx", "rank": 8, "score": 7.445700168609619}, {"content": "Title: Enfermedad cardiovascular en tiempos de COVID-19./ [Cardiovascular disease in times of COVID-19] Content: There are increasing reports of a drastic drop in consultations and cardiovascular procedures (including urgencies and emergencies) in regions affected by the COVID-19 pandemic, with a consequent marked increase in total mortality that is not fully explained by COVID-19. Cardiovascular disease leads the ranking in deaths in adults in Argentina with 280 deaths per day, and in recent decades we have reduced its mortality by 20-30% through various evidence-based interventions. Herein we conducted predictive analyses to understand what could be the consequences of a worse implementation of those interventions. We estimate that less control of cardiovascular risk factors from April to October 2020 could cause up to 10 500 new preventable cases of cardiovascular disease. In terms of myocardial infarction, a drop from 40% to 60% of the reperfusion treatment could increase mortality by 3% to 5%. A marginal 10% to 15% increase in relative risk of cardiovascular death would be equivalent to an excess of 6000 to 9000 preventable deaths. In conclusion, given the high prevalence and fatality of cardiovascular disease, even a small negative impact on the efficacy of its care will translate into large numbers of people affected in Argentina. It is necessary to inform the authorities and educate the public so cardiovascular diseases and their risk factors remain a health priority, as long as resources exist and minimizing the risk of contagion and spread of the virus.", "qid": 4, "docid": "62je92vo", "rank": 9, "score": 7.3403000831604}, {"content": "Title: [Cardiovascular disease in times of COVID-19]. Content: There are increasing reports of a drastic drop in consultations and cardiovascular procedures (including urgencies and emergencies) in regions affected by the COVID-19 pandemic, with a consequent marked increase in total mortality that is not fully explained by COVID-19. Cardiovascular disease leads the ranking in deaths in adults in Argentina with 280 deaths per day, and in recent decades we have reduced its mortality by 20-30% through various evidence-based interventions. Herein we conducted predictive analyses to understand what could be the consequences of a worse implementation of those interventions. We estimate that less control of cardiovascular risk factors from April to October 2020 could cause up to 10 500 new preventable cases of cardiovascular disease. In terms of myocardial infarction, a drop from 40% to 60% of the reperfusion treatment could increase mortality by 3% to 5%. A marginal 10% to 15% increase in relative risk of cardiovascular death would be equivalent to an excess of 6000 to 9000 preventable deaths. In conclusion, given the high prevalence and fatality of cardiovascular disease, even a small negative impact on the efficacy of its care will translate into large numbers of people affected in Argentina. It is necessary to inform the authorities and educate the public so cardiovascular diseases and their risk factors remain a health priority, as long as resources exist and minimizing the risk of contagion and spread of the virus.", "qid": 4, "docid": "bkglb1v6", "rank": 10, "score": 7.234499931335449}, {"content": "Title: COVID\u201019: what if the brain had a role in causing the deaths? Content: In the last few weeks Italy first, and then several other countries across the world, have been swept up by the deadly wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the illness named COVID-19, from the acronym CO (corona) VI (virus) D (disease) and 19 (year of the virus identification). The medical community is working day and night to assist affected people and experts in communicable diseases are striving in multiple ways to understand the progression of events leading to the lethal respiratory syndrome.", "qid": 4, "docid": "6t3jrmr7", "rank": 11, "score": 7.187099933624268}, {"content": "Title: Model studies on the COVID-19 pandemic in Sweden Content: We study the increases of infections and deaths in Sweden caused by COVID-19 with several different models: Firstly an analytical susceptible-infected (SI) model and the standard susceptible-infected-recovered (SIR) model. Then within the SIR framework we study the susceptible-infected-deceased (SID) correlations. All models reproduce well the number of infected cases and give similar predictions. What causes us deep concern is the large number of deaths projected by the SI and SID models. Our analysis shows that, irrespective of the possible uncertainty of our model prediction, the next few days can be critical for determining the future evolution of the death cases (Updated April 02).", "qid": 4, "docid": "u61qc8ey", "rank": 12, "score": 7.139400005340576}, {"content": "Title: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey Content: The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent's country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.", "qid": 4, "docid": "b54dymlu", "rank": 13, "score": 7.13670015335083}, {"content": "Title: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey Content: Abstract The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent\u2019s country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.", "qid": 4, "docid": "s5u57av2", "rank": 14, "score": 7.136699199676514}, {"content": "Title: Epidemiology and clinical features of coronavirus disease 2019 in children Content: Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.", "qid": 4, "docid": "jsyao6qu", "rank": 15, "score": 7.099800109863281}, {"content": "Title: COVID-19 in Immunocompromised Hosts: What We Know So Far Content: The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk for more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from cancer patients and solid organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid organ transplant recipients may be at increased risk of severe COVID-19 disease and death whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective, controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.", "qid": 4, "docid": "9jbuynvv", "rank": 16, "score": 7.035200119018555}, {"content": "Title: Epidemiology and Clinical Features of Coronavirus disease 2019 in Children Content: Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.", "qid": 4, "docid": "h2cm3cge", "rank": 17, "score": 7.019599914550781}, {"content": "Title: First comes the A, then the B: what we learned from the COVID-19 outbreak() Content: The SARS-CoV-2 epidemic, which has spread to many countries around the world, has hit Europe particularly hard. From our point of view, in a rural emergency department (with an annual patient census of around 25,000) in northeastern Italy, it is necessary to preserve the hospital and prevent it from becoming an outbreak of infection. In our experience, we reevaluated the negative predictive value of lung ultrasound to rule out lung involvement. Since severe acute respiratory failure appears to be the leading cause of death for COVID-19 patients, it is essential to focus on this clinical feature. We currently believe that a patient suspected of COVID-19, if he has a normal ultrasound examination (a so-called \"A-profile\"), can be discharged home to continue isolation and be treated without being hospitalized.", "qid": 4, "docid": "fao60udv", "rank": 18, "score": 6.946800231933594}, {"content": "Title: First comes the A, then the B: what we learned from the COVID-19 outbreak Content: The SARS-CoV-2 epidemic, which has spread to many countries around the world, has hit Europe particularly hard. From our point of view, in a rural emergency department (with an annual patient census of around 25,000) in northeastern Italy, it is necessary to preserve the hospital and prevent it from becoming an outbreak of infection. In our experience, we reevaluated the negative predictive value of lung ultrasound to rule out lung involvement. Since severe acute respiratory failure appears to be the leading cause of death for COVID-19 patients, it is essential to focus on this clinical feature. We currently believe that a patient suspected of COVID-19, if he has a normal ultrasound examination (a so-called \"A-profile\"), can be discharged home to continue isolation and be treated without being hospitalized.", "qid": 4, "docid": "oydinhno", "rank": 19, "score": 6.946799278259277}, {"content": "Title: [Covid-19 - deaths and analysis]. Content: Mortality from Covid-19 is monitored in detail and compared between countries with different strategies against the virus. There is, however, often a lack of understanding of what is required in terms of measures and interpretation to enable correct comparisons. The number of deaths from Covid-19 is affected by the testing strategy and many other things that differ between countries. Therefore, today, the most reliable source for monitoring and comparing mortality from Covid-19 is total mortality. In Sweden, there is good correspondence of Covid-19 deaths and total mortality, with a tendency to a higher total mortality indicating some under-reporting of Covid-19 mortality.", "qid": 4, "docid": "o72xreym", "rank": 20, "score": 6.927999973297119}, {"content": "Title: Evaluating the effect of public health intervention on the global-wide spread trajectory of Covid-19 Content: As COVID-19 evolves rapidly, the issues the governments of affected countries facing are whether and when to take public health interventions and what levels of strictness of these interventions should be, as well as when the COVID-19 spread reaches the stopping point after interventions are taken. To help governments with policy-making, we developed modified auto-encoders (MAE) method to forecast spread trajectory of Covid-19 of countries affected, under different levels and timing of intervention strategies. Our analysis showed public health interventions should be executed as soon as possible. Delaying intervention 4 weeks after March 8, 2020 would cause the maximum number of cumulative cases of death increase from 7,174 to 133,608 and the ending points of the epidemic postponed from Jun 25 to Aug 22.", "qid": 4, "docid": "44zduv27", "rank": 21, "score": 6.900199890136719}, {"content": "Title: Coronavirus disease (COVID\u201019) and neonate: What neonatologist need to know Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS\u2010CoV\u20102 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID\u201019) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID\u201019 infection in newborns and children.", "qid": 4, "docid": "1hwcp09t", "rank": 22, "score": 6.888599872589111}, {"content": "Title: Coronavirus disease (COVID-19) and neonate: What neonatologist need to know Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.", "qid": 4, "docid": "4qy35wdf", "rank": 23, "score": 6.888598918914795}, {"content": "Title: Total mortalitet b\u00e4ttre vid j\u00e4mf\u00f6relser \u00e4n d\u00f6d i covid-19./ [Covid-19 - deaths and analysis] Content: Mortality from Covid-19 is monitored in detail and compared between countries with different strategies against the virus. There is, however, often a lack of understanding of what is required in terms of measures and interpretation to enable correct comparisons. The number of deaths from Covid-19 is affected by the testing strategy and many other things that differ between countries. Therefore, today, the most reliable source for monitoring and comparing mortality from Covid-19 is total mortality. In Sweden, there is good correspondence of Covid-19 deaths and total mortality, with a tendency to a higher total mortality indicating some under-reporting of Covid-19 mortality.", "qid": 4, "docid": "xw244riy", "rank": 24, "score": 6.88100004196167}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 4, "docid": "fqs40ivc", "rank": 25, "score": 6.872300148010254}, {"content": "Title: Point-of-care lung ultrasound in three neonates with COVID-19 Content: Since March 2020, the world is involved in the COVID-19 pandemic, a disease caused by a novel virus called SARS-CoV-2. Some authors have described the ultrasonographic findings of COVID-19 pneumonia in adults and children, but data on neonates are lacking. Our objective was to describe the ultrasonographic lung pattern on newborns with SARS-CoV-2 infection during the COVID-19 pandemic. Newborns who tested positive for SARS-CoV-2 PCR in respiratory samples and were evaluated with point-of-care lung ultrasound (LU) from March to April 2020 were included. LU was performed bedside by a single investigator at the time of diagnosis and every 48 h during the first week following diagnosis. Six areas were studied. Three neonates were included. Infants' comorbidities included meconium aspiration syndrome, bronchopulmonary dysplasia, and Hirschsprung's disease. One required mechanical ventilation. No deaths occurred. LU showed B-lines, consolidation, and spared areas. No pneumothorax or pleural effusion was observedConclusions: LU could be of value when managing COVID-19 neonates. We describe the findings of lung ultrasound monitoring during the first week following diagnosis in three neonates with SARS-CoV-2 infection. What is known: \u00e2\u0080\u00a2 Lung ultrasound (LU) is a useful tool in COVID-19 management in adults. To date, no report on LU and neonates with SARS-CoV-2 infection has been published. What is new: \u00e2\u0080\u00a2 This study adds evidence about LU findings in neonates with SARS-CoV-2 infection.", "qid": 4, "docid": "pab56xyd", "rank": 26, "score": 6.842199802398682}, {"content": "Title: Dysphagia in COVID\u201019 \u2013multilevel damage to the swallowing network? Content: We read with great interest the article \u201cCOVID\u201019: what if the brain had a role in causing the deaths?\u201d by Tassorelli and co\u2010workers, in which the authors generate and summarize hypotheses how SARS\u2010CoV\u20102 may enter the peripheral and central nervous system and cause life\u2010threatening complications [1]. With this letter we would like to contribute to this discussion by highlighting how different complications of COVID\u201019 may result in damage to central and peripheral parts of the swallowing network leading to dysphagia in critically ill COVID\u2010survivors.", "qid": 4, "docid": "2427yjza", "rank": 27, "score": 6.830699920654297}, {"content": "Title: Mental health issues and psychological crisis interventions during the COVID-19 pandemic and earthquakes in Croatia/ Mentalno zdravlje i psiholo\u0161ke krizne intervencije tijekom COVID-19 pandemije i potresa u Hrvatskoj Content: The newly discovered coronavirus, now called SARS-CoV-2, was first detected in Wuhan, China as a cause of severe acute respiratory syndrome, disease called COVID-19. From the beginning of 2020 it rapidly spread, affecting the whole world, but with a major impact in Europe and North America. At the moment of writing, there are more than 2 million confirmed cases with more than 125.000 confirmed deaths related to COVID-19 globally. In Croatia, there are currently 1.741 confirmed cases with 34 deaths related to the virus. The COVID-19 rapid spread and magnitude of pandemic unleashed panic among people which warrants public health officials to also address the epidemic of fear. Research on the psychological reactions to previous epidemics and pandemics suggests that various psychological factors may play a role in coronaphobia. Nov-elty and uncertainty what the unknown brings is likely the cause of COVID-19 fear. With the sharp increase in number of affected persons by pandemic, both infected or suspected cases in isolation, fear and anxiety grew in general population, which warranted a significant increase in need for psychiatric support for both patients and medical staff. After initial stabilization of the situation and a prompt response to increased needs for mental support, during this time of pandemic, self-isolations and imposed social distancing, the strongest earthquake this city has experienced in the last 140 years hit Croatian capital Zagreb. During these trying times, maintaining good mental health of both medical personnel as well as the general population is crucial for both health and mental damage control. In Croatia, crisis interventions aimed for those most exposed to mental impact of pandemic and natural disasters is limited.", "qid": 4, "docid": "gokevnzw", "rank": 28, "score": 6.818900108337402}, {"content": "Title: SARS\u2010CoV\u20102: What do we know so far? Content: We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and patients with underlying comorbidities are at a higher risk of death. We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia.", "qid": 4, "docid": "9pdakwmb", "rank": 29, "score": 6.803400039672852}, {"content": "Title: Analysis of Covid-19 and non-Covid-19 viruses including influenza viruses to see the influence of intensive preventive measures among Japanese Content: Severe acute respiratory coronavirus 2 (SARS-CoV-2) spread and cause death in worldwide. The preventative measures and infection control are underway throughout the society and there are signs of convergence in some areas. Other viruses as well as SARS-CoV-2 cause cold-like symptoms and spread in winter. However, it is unclear to what extent SARS-CoV-2, influenza virus and other causative viruses have been prevailed since the preventative measures were implemented. In this study, we conducted multiples PCR and quantitative reverse transcription PCR using nasal swabs from 191 patients with cold-like symptoms in Japan to reveal the causative viruses. As a result, at least one virus were detected in 40 out of 191 (21%) patients. Of these, we frequently identified the human rhinovirus / enterovirus (5.8%, n=11), SARS-CoV-2 (4.2%, n=8) and human metapneumovirus (3.7%, n=7). On the other hand, no influenza virus was detected. These results shows the prevalence of causative viruses after the social preventative measures and implies the difference of infectivity between SARS-CoV-2 and influenza virus.", "qid": 4, "docid": "otjctvr8", "rank": 30, "score": 6.757900238037109}, {"content": "Title: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. Content: Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.", "qid": 4, "docid": "92tvskxw", "rank": 31, "score": 6.741799831390381}, {"content": "Title: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 Content: Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781\u00e2\u0080\u00af000 total deaths in the United States from March 1 to May 30, 2020, representing 122\u00e2\u0080\u00af300 (95% prediction interval, 116\u00e2\u0080\u00af800-127\u00e2\u0080\u00af000) more deaths than would typically be expected at that time of year. There were 95\u00e2\u0080\u00af235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.", "qid": 4, "docid": "f74q6nwj", "rank": 32, "score": 6.7417988777160645}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Since the emergence of the COVID-19 pandemic in December 2019 in Wuhan, China, there have been nearly 6,663,304 confirmed cases of COVID-19, including 392,802 deaths, worldwide as of 10:00 CEST 06 June 2020. In Africa, 152,442 COVID-19 cases and 4334 deaths have been reported as of 02 June 2020. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, and the rest of world, has had to swiftly undertake the necessary measures to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting systems, and insufficient numbers of medical staff. The COVID-19 pandemic poses a great threat to most African countries, from cities to rural areas, and has created a strong demand on already scarce resources. Intense mobilization of additional resources is required to implement established emergency contingency measures. Measures to prevent the spread of COVID-19 include closure of borders and restricting movement of people within a country; this has resulted in the tourism sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 4, "docid": "h3czhqtt", "rank": 33, "score": 6.739099979400635}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 4, "docid": "gnaubzah", "rank": 34, "score": 6.725800037384033}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 4, "docid": "hlhhvmtu", "rank": 35, "score": 6.725799083709717}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Abstract Since the emergence of the pandemic in December 2019 in Wuhan, China, as of 10:00 CEST, June 6, 2020, there have been nearly 6,663,304 confirmed cases of COVID-19 including 392,802 deaths worldwide. In Africa, as of June 2, 2020, a total of 152,442 COVID-19 cases and 4334 deaths have been reported. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, together with the rest of world have had to swiftly undertake measures necessary to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting system and insufficient number of medical staff. The COVID-19 pandemic poses a great threat to most African countries from cities to rural areas and has created a strong demand on already scarce resources and requires an intense mobilization of additional resources to implement established emergency contingency measures. Closure of borders and movements of people restrictions within the country as measures to prevent the spread of COVID-19; this has resulted in the sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 4, "docid": "juvmabdq", "rank": 36, "score": 6.714799880981445}, {"content": "Title: Regional analysis of COVID-19 in France from fit of hospital data with different evolutionary models Content: The SIR evolutionary model predicts too sharp a decrease of the fractions of people infected with COVID-19 in France after the start of the national lockdown, compared to what is observed. I fit the daily hospital data: arrivals in regular and critical care units, releases and deaths, using extended SEIR models. These involve ratios of evolutionary timescales to branching fractions, assumed uniform throughout a country, and the basic reproduction number, $R_0$, before and during the national lockdown, for each region of France. The joint-region Bayesian analysis allows precise evaluations of the time/fraction ratios and pre-hospitalized fractions. The hospital data are well fit by the models, except the arrivals in critical care, which decrease faster than predicted, indicating better treatment over time. Averaged over France, the analysis yields $R_0$= 3.4$\\pm$0.1 before the lockdown and 0.65$\\pm$0.04 (90% c.l.) during the lockdown, with small regional variations. On 11 May 2020, the Infection Fatality Rate in France was 4 $\\pm$1% (90% c.l.), while the Feverish vastly outnumber the Asymptomatic, contrary to the early phases. Without the lockdown nor social distancing, over 2 million deaths from COVID-19 would have occurred throughout France, while a lockdown that would have been enforced 10 days earlier would have led to less than 1000 deaths. The fraction of immunized people reached a plateau below 1% throughout France (3% in Paris) by late April 2020 (95% c.l.), suggesting a lack of herd immunity. The widespread availability of face masks on 11 May, when the lockdown was partially lifted, should keep $R_0$ below unity if at least 46% of the population wear them outside their home. Otherwise, without enhanced other social distancing, a second wave is inevitable and cause the number of deaths to triple between early May and October (if $R_0$=1.2) or even late June (if $R_0$=2).", "qid": 4, "docid": "p1wz8yrj", "rank": 37, "score": 6.703100204467773}, {"content": "Title: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters Content: OBJECTIVE: To evaluate the relative risk of COVID-19 death in people <65 years old versus older individuals in the general population, to provide estimates of absolute risk of COVID-19 death at the population level, and to understand what proportion of COVID-19 deaths occur in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Countries and US states or major cities with at least 250 COVID-19 deaths as of 4/4/2020 and with information available on death counts according to age strata, allowing to calculate the number of deaths in people with age <65. Data were available for Belgium, Germany, Italy, Netherlands, Portugal, Spain, Sweden, and Switzerland, as well as Louisiana, Michigan, Washington states and New York City as of April 4, 2020. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths that occur in people <65 years old; relative risk of COVID-19 death in people <65 versus \u226565 years old; absolute risk of death in people <65 and in those \u226580 years old in the general population as of 4/4/2020; absolute death risk expressed as equivalent of death risk from driving a motor vehicle. RESULTS: Individuals with age <65 account for 5%-9% of all COVID-19 deaths in the 8 European epicenters, and approach 30% in three US hotbed locations. People <65 years old had 34- to 73-fold lower risk than those \u226565 years old in the European countries and 13- to 15-fold lower risk in New York City, Louisiana and Michigan. The absolute risk of COVID-19 death ranged from 1.7 per million for people <65 years old in Germany to 79 per million in New York City. The absolute risk of COVID-19 death for people \u226580 years old ranged from approximately 1 in 6,000 in Germany to 1 in 420 in Spain. The COVID-19 death risk in people <65 years old during the period of fatalities from the epidemic was equivalent to the death risk from driving between 9 miles per day (Germany) and 415 miles per day (New York City). People <65 years old and not having any underlying predisposing conditions accounted for only 0.3%, 0.7%, and 1.8% of all COVID-19 deaths in Netherlands, Italy, and New York City. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in the hotbeds of the pandemic and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.", "qid": 4, "docid": "2cwvga0k", "rank": 38, "score": 6.6956000328063965}, {"content": "Title: COVID-19: Lessons for the climate change emergency Content: The ongoing COVID-19 outbreak pandemic is now a global crisis. It has caused 9+ million confirmed cases and 400,000+ deaths at the time of writing and triggered unprecedented preventative measures that have confined a substantial portion of the global population and established \u2018social distancing\u2019 as a new global behavioral norm. The COVID-19 crisis has affected all aspects of everyday life and work, and heavily impacted the global economy. This crisis also offers unprecedented insights into how the global climate crisis may be managed, as there are many parallels between the COVID-19 crisis and what we expect from the imminent global climate emergency. Reflecting upon the challenges of today's crisis may help us better prepare for the future. Here we compile a list, by no means comprehensive, of the similarities and differences between the two crises, and the lessons we can learn from them: (i) High momentum trends, (ii) Irreversible changes, (iii) Social and spatial inequality, (iv) Weakening of international solidarity, and (v) Less costly to prevent than to cure.", "qid": 4, "docid": "dgd5ohb3", "rank": 39, "score": 6.692399978637695}, {"content": "Title: Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain. Content: Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.", "qid": 4, "docid": "ix9x25sc", "rank": 40, "score": 6.692399024963379}, {"content": "Title: COVID-19: Lessons for the climate change emergency Content: The ongoing COVID-19 outbreak pandemic is now a global crisis. It has caused 9+ million confirmed cases and 400,000+ deaths at the time of writing and triggered unprecedented preventative measures that have confined a substantial portion of the global population and established 'social distancing' as a new global behavioral norm. The COVID-19 crisis has affected all aspects of everyday life and work, and heavily impacted the global economy. This crisis also offers unprecedented insights into how the global climate crisis may be managed, as there are many parallels between the COVID-19 crisis and what we expect from the imminent global climate emergency. Reflecting upon the challenges of today's crisis may help us better prepare for the future. Here we compile a list, by no means comprehensive, of the similarities and differences between the two crises, and the lessons we can learn from them: (i) High momentum trends, (ii) Irreversible changes, (iii) Social and spatial inequality, (iv) Weakening of international solidarity, and (v) Less costly to prevent than to cure.", "qid": 4, "docid": "mwohtppj", "rank": 41, "score": 6.6923980712890625}, {"content": "Title: Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain Content: Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.", "qid": 4, "docid": "qzxvh2qc", "rank": 42, "score": 6.692397117614746}, {"content": "Title: COVID-19: what if the brain had a role in causing the deaths? Content:", "qid": 4, "docid": "nay6x9y1", "rank": 43, "score": 6.688600063323975}, {"content": "Title: Population-Level Mortality Rates from Novel Coronavirus (COVID-19) in South Korea Content: Background: South Korea was among the first countries to report a case of the novel coronavirus (COVID-19) outside of China. As of 22 March, 2020, South Korea reported 8897 confirmed cases of and 104 deaths from COVID-19. Methods: We collected the number of laboratory-confirmed cases and deaths in South Korea from the World Health Organization (as of 21 March, 2020) and case distribution and fatality rates by age from the Korean Center for Disease Control and Prevention (as of 22 March, 2020). We estimated population-level mortality rates by fitting a negative binomial regression model with the number of deaths as the outcome and population by age as an offset. We then calculated the age-standardized death rate (ASDR) based on the current COVID-19 figures and for alternative scenarios of increased prevalence. Findings: The COVID-19 population-level mortality rate (per 100,000 person-years) increased with age: from 0.1 deaths among 30-39 year olds to 9.5 deaths among \u226580 year olds. The ASDR (per 100,000 person-years) was 0.8 deaths. The ASDR would increase to 52.0 deaths at a 1% prevalence (becoming the third leading cause of death) and 155.9 deaths at 3% prevalence (becoming the leading cause of death). Interpretation: Currently, the population-level mortality burden of COVID-19 in South Korea, as measured by the ASDR, was relatively low compared to other causes of death partly due to the low prevalence of COVID-19. If the prevalence increases from another outbreak, the mortality burden could increase substantially and surpass other leading causes.", "qid": 4, "docid": "lizwiate", "rank": 44, "score": 6.687600135803223}, {"content": "Title: Public Health Responses to COVID-19 Outbreaks on Cruise Ships \u2014 Worldwide, February\u2013March 2020 Content: What is already known about this topic? Cruise ships are often settings for outbreaks of infectious diseases because of their closed environment and contact between travelers from many countries What is added by this report? More than 800 cases of laboratory-confirmed COVID-19 cases occurred during outbreaks on three cruise ship voyages, and cases linked to several additional cruises have been reported across the United States Transmission occurred across multiple voyages from ship to ship by crew members;both crew members and passengers were affected;10 deaths associated with cruise ships have been reported to date What are the implications for public health practice? Outbreaks of COVID-19 on cruise ships pose a risk for rapid spread of disease beyond the voyage Aggressive efforts are required to contain spread All persons should defer all cruise travel worldwide during the COVID-19 pandemic", "qid": 4, "docid": "9b6j5lk0", "rank": 45, "score": 6.634399890899658}, {"content": "Title: What has the covid-19 pandemic taught us about adopting preventive measures?/ \u00bflo que la pandemia covid-19 nos ense\u00f1\u00f3 sobre la adopci\u00f3n de las medidas preventivas?/ O que a pandemia da covid-19 tem nos ensinado sobre ado\u00e7\u00e3o de medidas de precau\u00e7\u00e3o? Content: ABSTRACT Objective: to analyze the COVID-19 pandemic and what we have (re)learned from the world experience of adopting prevention measures recommended by the World Health Organization as well as the epidemiological overview in the world, in Latin America and in Brazil. Results: the World Health Organization has pointed out that the path to reduce the speed of circulation of the virus, control and decrease in the number of cases and deaths resulting from this pandemic can only be accomplished with mass adoption of fundamental measures that include hand hygiene, alcohol gel use, cough etiquette, cleaning surfaces, avoiding agglomerations and social distancing. The epidemiological curve of the disease clearly shows the devastating proportions in Italy, Spain and the United States, surpassing China in death records, due to the delay in adopting the aforementioned measures. In Brazil, the rapid progression in relation to the world and Latin America points to an important increase in the number of cases. Conclusion: this is possibly the most serious pandemic in recent human history, and its course can be influenced by the rigor in adopting individual and collective behavioral measures.", "qid": 4, "docid": "41ycjpt9", "rank": 46, "score": 6.61329984664917}, {"content": "Title: Treatment of the Novel COVID-19: Why Costa Rica\u2019s Proposal for the Creation of a Global Pooling Mechanism Deserves Serious Consideration? Content: The COVID-19 is causing not only deaths and fear but also economic and social harm across the globe. Lockdowns, travel restrictions, quarantines, social distancing, and other strict public-health measures are playing their part in delaying the spread of infection, but a safe and potent vaccine, effective therapeutics, point-of-care diagnostics, and other health products are desperately needed because it may not be practically possible for governments to extend these measures for an indefinite period of time. On March 23, Costa Rica submitted a proposal to the Director-General of the World Health Organization for the creation of a global pooling mechanism in order to facilitate access to and use of intellectual property, trade-secret know how, regulatory data, cell lines, product blueprints, and other proprietary data for technologies that are useful for the detection, prevention, control and treatment of the COVID-19 pandemic. This study critically evaluates Costa Rica\u2019s proposal and endeavours to briefly answer the following questions: Why Costa Rica\u2019s proposal deserves serious consideration? To what extent this proposal addresses some of the key concerns related to the COVID-19? To what extent this proposal is practically feasible?", "qid": 4, "docid": "lszibfbc", "rank": 47, "score": 6.606299877166748}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index &#8805;40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 4, "docid": "3jwl97qb", "rank": 48, "score": 6.5802998542785645}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy. Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index \u226540), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 4, "docid": "7ofa04l1", "rank": 49, "score": 6.580298900604248}, {"content": "Title: Human and novel coronavirus infections in children: a review Content: Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS: 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Gu\u00e9rin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.", "qid": 4, "docid": "2zaxn6tq", "rank": 50, "score": 6.560800075531006}, {"content": "Title: Human and novel coronavirus infections in children: a review. Content: Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Gu\u00e9rin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.", "qid": 4, "docid": "5w194etz", "rank": 51, "score": 6.5607991218566895}, {"content": "Title: COVID-19 pandemic: what consequences for cardiac rehabilitation? Content: The ongoing COVID-19 pandemic spreading all around the world has stressed over its capabilities and determined profound changes in the health systems in all countries and has caused hundreds of thousand deaths. Health professionals have been called to a tremendous effort to deal with this emergency, often contaminating or succumbing themselves to the disease.", "qid": 4, "docid": "87v0260x", "rank": 52, "score": 6.560400009155273}, {"content": "Title: Rapid estimation of excess mortality in times of COVID-19 in Portugal - Beyond reported deaths Content: Background: One month after the first COVID-19 infection was recorded, Portugal counted 18 051 cases and 599 deaths from COVID-19. To understand the overall impact on mortality of the pandemic of COVID-19, we estimated the excess mortality registered in Portugal during the first month of the epidemic, from March 16 until April 14 using two different methods. Methods: We compared the observed and expected daily deaths (historical average number from daily death registrations in the past 10 years) and used 2 standard deviations confidence limit for all-cause mortality by age and specific mortality cause, considering the last 6 years. An adapted ARIMA model was also tested to validate the estimated number of all-cause deaths during the study period. Results: Between March 16 and April 14, there was an excess of 1,255 all-cause deaths, 14% more than expected. The number of daily deaths often surpassed the 2 standard deviations confidence limit. The excess mortality occurred mostly in people aged 75+. Forty-nine percent (49%) of the estimated excess deaths were registered as due to COVID-19, The other 51% registered as other natural causes. Conclusion: Even though Portugal took early containment measures against COVID-19, and the population complied massively with those measures, there was significant excess mortality during the first month of the pandemic, mostly among people aged 75+. Only half of the excess mortality was registered as directly due do COVID-19.", "qid": 4, "docid": "lluhdln7", "rank": 53, "score": 6.549499988555908}, {"content": "Title: A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic Content: Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths.1 COVID-19 causes a severe pneumonia characterized by fever, cough and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extrapulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multiorgan manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What is more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.", "qid": 4, "docid": "4r6jbv44", "rank": 54, "score": 6.548600196838379}, {"content": "Title: A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic Content: Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.", "qid": 4, "docid": "bjyzrmsb", "rank": 55, "score": 6.5485992431640625}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u20112 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 4, "docid": "e6k1bp9n", "rank": 56, "score": 6.539999961853027}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u00ad2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 4, "docid": "zt9mxom1", "rank": 57, "score": 6.539999008178711}, {"content": "Title: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study Content: OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (\u226565 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.", "qid": 4, "docid": "t22hwoeb", "rank": 58, "score": 6.534200191497803}, {"content": "Title: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study Content: OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (&#8805;65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.", "qid": 4, "docid": "txt4ae7k", "rank": 59, "score": 6.534199237823486}, {"content": "Title: Novel Coronavirus (nCoV): a Bitter Old Enemy in a New Avatar Content: Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.", "qid": 4, "docid": "1ij25a7u", "rank": 60, "score": 6.519199848175049}, {"content": "Title: Global service\u2010learning and COVID\u201019\u2014What the future might look like? Content: The novel coronavirus disease (COVID-19) pandemic has disrupted travel and caused marked death and disability globally. The economic impact of this change has forced universities to operate differently in how they conduct their operations and deliver education to students (Jackson et al. 2020). Leveraging digital modalities has been crucial in achieving business continuity.", "qid": 4, "docid": "z4mj4xgv", "rank": 61, "score": 6.518499851226807}, {"content": "Title: The clinical characteristics and mortal causes analysis of COVID-19 death patients Content: Abstract Purpose: Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients. Patients and methods: The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database. Results: 159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients. Conclusion: Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment . Keywords: COVID-19, SARS-Cov-2, death, coexisting disorder, cause of death", "qid": 4, "docid": "dtlwjndn", "rank": 62, "score": 6.515900135040283}, {"content": "Title: Excess mortality in England and Wales during the first wave of the COVID-19 pandemic Content: Background Deaths during the COVID-19 pandemic result directly from infection and exacerbation of other diseases and indirectly from deferment of care for other conditions, and are socially and geographically patterned. We quantified excess mortality in regions of England and Wales during the pandemic, for all causes and for non-COVID-19 associated deaths. Methods Weekly mortality data for 1 Jan 2010 to 1 May 2020 for England and Wales were obtained from the Office of National Statistics. Mean-dispersion negative binomial regressions were used to model death counts based on pre-pandemic trends and exponentiated linear predictions were subtracted from: i) all-cause deaths; and ii) all-cause deaths minus COVID-19 related deaths for the pandemic period (07-13 March to 25 April to 8 May). Findings Between 7 March and 8 May 2020, there were 47,243 (95%CI: 46,671 to 47,815) excess deaths in England and Wales, of which 9,948 (95%CI: 9,376 to 10,520) were not associated with COVID-19. Overall excess mortality rates varied from 49 per 100,000 (95%CI: 49 to 50) in the South West to 102 per 100,000 (95%CI: 102 to 103) in London. Non-COVID-19 associated excess mortality rates ranged from -1 per 100,000 (95%CI: -1 to 0) in Wales (i.e. mortality rates were no higher than expected) to 26 per 100,000 (95%CI: 25 to 26) in the West Midlands. Interpretation The COVID-19 pandemic has had markedly different impacts on the regions of England and Wales, both for deaths directly attributable to COVID-19 infection and for deaths resulting from the national public health response.", "qid": 4, "docid": "n6z0r08o", "rank": 63, "score": 6.484000205993652}, {"content": "Title: Age- and sex-specific total mortality impacts of the early weeks of the Covid-19 pandemic in England and Wales: Application of a Bayesian model ensemble to mortality statistics Content: Background: The Covid-19 pandemic affects mortality directly through infection as well as through changes in the social, environmental and healthcare determinants of health. The impacts on mortality are likely to vary, in both magnitude and timing, by age and sex. Our aim was to estimate the total mortality impacts of the pandemic, by sex, age group and week. Methods: We developed an ensemble of 16 Bayesian models that probabilistically estimate the weekly number of deaths that would be expected had the Covid-19 pandemic not occurred. The models account for seasonality of death rates, medium-long-term trends in death rates, the impact of temperature on death rates, association of death rates in each week on those in preceding week(s), and the impact of bank holidays. We used data from January 2010 through mid-February 2020 (i.e., week starting 15th February 2020) to estimate the parameters of each model, which was then used to predict the number of deaths for subsequent weeks as estimates of death rates if the pandemic had not occurred. We subtracted these estimates from the actual reported number of deaths to measure the total mortality impact of the pandemic. Results: In the week that began on 21st March, the same week that a national lockdown was put in place, there was a >92% probability that there were more deaths in men and women aged [\u2265]45 years than would occur in the absence of the pandemic; the probability was 100% from the subsequent week. Taken over the entire period from mid-February to 8th May 2020, there were an estimated [~] 49,200 (44,700-53,300) or 43% (37-48) more deaths than would be expected had the pandemic not taken place. 22,900 (19,300-26,100) of these deaths were in females (40% (32-48) higher than if there had not been a pandemic), and 26,300 (23,800-28,700) in males (46% (40-52) higher). The largest number of excess deaths occurred among women aged >85 years (12,400; 9,300-15,300), followed by men aged >85 years (9,600; 7,800-11,300) and 75-84 years (9,000; 7,500-10,300). The cause of death assigned to the majority (37,295) of these excess deaths was Covid-19. There was nonetheless a >99.99% probability that there has been an increase in deaths assigned to other causes in those aged [\u2265]45 years. However, by the 8th of May, the all-cause excess mortality had become virtually equal to deaths assigned to Covid-19, and non-Covid excess deaths had diminished to close to zero, or possibly become negative, in all age-sex groups. Interpretation: The death toll of Covid-19 pandemic, in middle and older ages, is substantially larger than the number of deaths reported as a result of confirmed infection, and was visible in vital statistics when the national lockdown was put in place. When all-cause mortality is considered, the mortality impact of the pandemic on men and women is more similar than when comparing deaths assigned to Covid-19 as underlying cause of death.", "qid": 4, "docid": "h02qy4z0", "rank": 64, "score": 6.483500003814697}, {"content": "Title: Forecasting COVID-19 impact on hospital bed-days, ICU-days, ventilator-days and deaths by US state in the next 4 months Content: Key Points Question: Assuming social distancing measures are maintained, what are the forecasted gaps in available health service resources and number of deaths from the COVID-19 pandemic for each state in the United States? Findings: Using a statistical model, we predict excess demand will be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds at the peak of COVID-19. Peak ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674) ventilators. Peak demand will be in the second week of April. We estimate 81,114 (95% UI 38,242 to 162,106) deaths in the United States from COVID-19 over the next 4 months. Meaning: Even with social distancing measures enacted and sustained, the peak demand for hospital services due to the COVID-19 pandemic is likely going to exceed capacity substantially. Alongside the implementation and enforcement of social distancing measures, there is an urgent need to develop and implement plans to reduce non-COVID-19 demand for and temporarily increase capacity of health facilities. Abstract Importance: This study presents the first set of estimates of predicted health service utilization and deaths due to COVID-19 by day for the next 4 months for each state in the US. Objective: To determine the extent and timing of deaths and excess demand for hospital services due to COVID-19 in the US. Design, Setting, and Participants: This study used data on confirmed COVID-19 deaths by day from WHO websites and local and national governments; data on hospital capacity and utilization for US states; and observed COVID-19 utilization data from select locations to develop a statistical model forecasting deaths and hospital utilization against capacity by state for the US over the next 4 months. Exposure(s): COVID-19. Main outcome(s) and measure(s): Deaths, bed and ICU occupancy, and ventilator use. Results: Compared to licensed capacity and average annual occupancy rates, excess demand from COVID-19 at the peak of the pandemic in the second week of April is predicted to be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds. At the peak of the pandemic, ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674). The date of peak excess demand by state varies from the second week of April through May. We estimate that there will a total of 81,114 (95% UI 38,242 to 162,106) deaths from COVID-19 over the next 4 months in the US. Deaths from COVID-19 are estimated to drop below 10 deaths per day between May 31 and June 6. Conclusions and Relevance: In addition to a large number of deaths from COVID-19, the epidemic in the US will place a load well beyond the current capacity of hospitals to manage, especially for ICU care. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. These are urgently needed given that peak volumes are estimated to be only three weeks away. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures in all states that have not done so already within the next week and maintenance of these measures throughout the epidemic, emphasizing the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.", "qid": 4, "docid": "sfv9tu3t", "rank": 65, "score": 6.475100040435791}, {"content": "Title: Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis Content: Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.", "qid": 4, "docid": "tsd6sjcx", "rank": 66, "score": 6.470399856567383}, {"content": "Title: Initial experiences of US neurologists in practice during the COVID-19 pandemic via survey. Content: BACKGROUND The current coronavirus disease of 2019 (COVID-19) pandemic has caused widespread disease and death. Rapid increases in patient volumes have exposed weaknesses in healthcare systems and challenged our ability to provide optimal patient care and adequate safety measures to healthcare workers (HCWs). OBJECTIVE To test the hypothesis that US neurologists were experiencing significant challenges with lack of personal protective equipment (PPE), rapid changes in practice and varying institutional protocols, we conducted this survey study. METHODS A 36-item survey was distributed to neurologists around the US through various media platforms. RESULTS Over a one-week period, 567 responses were received. Of these, 56% practiced in academia. A total of 87% had access to PPE with 45% being asked to reuse PPE due to shortages. The pandemic caused rapid changes in practice, most notably a shift towards providing care by teleneurology, although a third experienced challenges in transitioning to this model. Wide variations were noted both in testing and in the guidance provided for the exposed, sick or vulnerable HCWs. Notably, 59% of respondents felt that their practices were doing what they could, although 56% did not feel safe taking care of patients. CONCLUSIONS Results from our survey demonstrate significant variability in preparedness and responsiveness to the COVID-19 pandemic in neurology, impacted by region, health care setting and practice model. Practice guidelines from professional societies and other national entities are needed to improve protection for physicians and their patients, promote recommended practice changes during a pandemic, and optimize future preparedness for public health emergencies.", "qid": 4, "docid": "21lnf8gw", "rank": 67, "score": 6.4664998054504395}, {"content": "Title: Initial experiences of US neurologists in practice during the COVID-19 pandemic via survey Content: BACKGROUND: The current coronavirus disease of 2019 (COVID-19) pandemic has caused widespread disease and death. Rapid increases in patient volumes have exposed weaknesses in healthcare systems and challenged our ability to provide optimal patient care and adequate safety measures to healthcare workers (HCWs). OBJECTIVE: To test the hypothesis that US neurologists were experiencing significant challenges with lack of personal protective equipment (PPE), rapid changes in practice and varying institutional protocols, we conducted this survey study. METHODS: A 36-item survey was distributed to neurologists around the US through various media platforms. RESULTS: Over a one-week period, 567 responses were received. Of these, 56% practiced in academia. A total of 87% had access to PPE with 45% being asked to reuse PPE due to shortages. The pandemic caused rapid changes in practice, most notably a shift towards providing care by teleneurology, although a third experienced challenges in transitioning to this model. Wide variations were noted both in testing and in the guidance provided for the exposed, sick or vulnerable HCWs. Notably, 59% of respondents felt that their practices were doing what they could, although 56% did not feel safe taking care of patients. CONCLUSIONS: Results from our survey demonstrate significant variability in preparedness and responsiveness to the COVID-19 pandemic in neurology, impacted by region, health care setting and practice model. Practice guidelines from professional societies and other national entities are needed to improve protection for physicians and their patients, promote recommended practice changes during a pandemic, and optimize future preparedness for public health emergencies.", "qid": 4, "docid": "bqf43ttw", "rank": 68, "score": 6.466498851776123}, {"content": "Title: Excess mortality and potential undercounting of COVID-19 deaths by demographic group in Ohio Content: Background: There are significant gaps in our understanding of the mortality effects of COVID-19 due to evolving diagnosis criteria, shortages of testing supplies, and challenges faced by physicians in treating patients in crisis environments. Accurate information on the number of deaths caused by COVID-19, both population wide and for demographic subgroups, is vital for policy makers and health care providers. Methods: We performed a retrospective study of weekly data for Ohio, a large American state. To estimate expected mortality in 2020 we employed data from 2010 through 2019, adjusted for secular trends and seasonality. We estimated excess mortality as the number of observed deaths less the number of expected deaths. We conducted the analysis for the entire population and by gender, race, age, and county of residence. Findings: We estimated 1,485 (95% CI 680-2,345) excess all-cause deaths in Ohio from March 15, 2020 through May 23, 2020. When limited to deaths due to natural causes, the estimated excess number of deaths increased to 2,504 (95% CI 1,633-3,221), reflecting the countervailing effect of a decrease in deaths due to external causes. While the largest number excess of deaths was observed in the 80+ age group, excess deaths comprised 45.3% (95% CI 21.8-60.9) of observed deaths in the groups corresponding to ages between 20 and 49 years old. Our estimate of 729 (95% CI 355-966) excess deaths for this group substantially exceeds the reported number of COVID-19 deaths of 51. We found elevated excess deaths for older individuals, blacks, and males. Interpretation: Our methodology addressed some of the challenges of estimating the number of deaths caused by COVID-19. Our finding of high proportional levels of excess deaths among younger age groups suggests that increases in the infection rates for this cohort may have a greater mortality impact than expected. Funding: None.", "qid": 4, "docid": "jjwz5jrr", "rank": 69, "score": 6.411799907684326}, {"content": "Title: TRACKing Excess Deaths (TRACKED): an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom Content: Aim: We aimed to describe trends of excess mortality in the United Kingdom (UK) stratified by nation and cause of death, and to develop an online tool for reporting the most up to date data on excess mortality. Methods: Population statistics agencies in the UK including the Office for National Statistics (ONS), National Records of Scotland (NRS), and Northern Ireland Statistics and Research Agency (NISRA) publish weekly data on deaths. We used mortality data up to 22nd May in the ONS and the NISRA and 24th May in the NRS. Crude mortality for non-COVID deaths (where there is no mention of COVID-19 on the death certificate) calculated. Excess mortality defined as difference between observed mortality and expected average of mortality from previous 5 years. Results: There were 56,961 excess deaths and 8,986 were non-COVID excess deaths. England had the highest number of excess deaths per 100,000 population (85) and Northern Ireland the lowest (34). Non-COVID mortality increased from 23rd March and returned to the 5-year average on 10th May. In Scotland, where underlying cause mortality data besides COVID-related deaths was available, the percentage excess over the 8-week period when COVID-related mortality peaked was: dementia 49%, other causes 21%, circulatory diseases 10%, and cancer 5%. We developed an online tool (TRACKing Excess Deaths - TRACKED) to allow dynamic exploration and visualisation of the latest mortality trends. Conclusions: Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.", "qid": 4, "docid": "v76ech81", "rank": 70, "score": 6.4095001220703125}, {"content": "Title: COVID-19, coagulopathy and venous thromboembolism: more questions than answers Content: The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. However, some relevant issues on the relationships between COVID-19, coagulopathy and VTE have yet to be fully elucidated. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence. This review discusses the most recent findings of basic and clinical research about the COVID-associated coagulopathy, to foster a more thorough knowledge of the mechanisms underlying this compelling disease.", "qid": 4, "docid": "camofa8f", "rank": 71, "score": 6.402200222015381}, {"content": "Title: [What to do about the deceased in suspected, probable and confirmed COVID-19 cases]. Content: The SARS-CoV-2 beta-coronavirus outbreak, which first appeared in Wuhan, China, in late 2019, was declared a pandemic by the World Health Organization on March 11, 2020. The first confirmed case of COVID-19 was reported in Hungary on 4 March 2020, and the first patient infected with a new type of coronavirus died on 15 March. At the time of the deceased's death, there was no central, uniform directive clarifying the range of precautions required or providing a clear description of the safe handling of the corpse. Transporting the dead to a pathology department, storing them, possibly dissecting them, and then placing them in their final resting place, how these raise countless questions. The current legislation on communicable diseases and actions on the dead does not provide sufficient information on the performance of tasks after the death of a COVID-19 infected patient. On March 19, the national chief medical officer suspended the autopsies, except for forensic autopsies, but transportation and storage remained a problem. Although on March 21, 2020, the Department of Pathology of the Health Professional College of the Ministry of Human Resources issued a formal procedure, the recommendations contained therein represent a narrower spectrum of literature and need to be supplemented in several places. Unfortunately, data on post-mortem procedures are also under-represented in the international literature, given their importance. Another problem is that in the articles written for the treatment of the victims of crisis situations caused by epidemics, the available algorithms take into account different organizational and resource possibilities in addition to the legal environment different from Hungary, which circumstances make domestic adaptation significantly more difficult. In our article, in addition to the literature review, we formulate suggestions and recommendations for healthcare professionals involved in the treatment of COVID-19 suspected, probable and confirmed patients, as well as potentially affected pathology departments, which increase the safety of providers. * Orv Hetil. 2020; 161 (17): 713-722.", "qid": 4, "docid": "9y0ejtty", "rank": 72, "score": 6.39900016784668}, {"content": "Title: What variables can better predict the number of infections and deaths worldwide by SARS-CoV-2? Variation through time Content: Lack of knowledge is the main problem we face in the global Covid-19 pandemic. SARS-CoV-2 is a new virus of which there were no previous studies. Using data from 50 very different countries and by means of a regression analysis, we studied the degree to which a series of variables (health indicators, environmental parameters, economic and social indicators, general characteristics of the country) were able to predict the number of people infected and killed by Covid-19. We also studied how these variables were changing their ability to predict the number of infected and dead by covid-19 during a 3 months period (March, April, May). The number of deaths by Covid-19 can always be predicted with great accuracy from the number of infected, regardless of the characteristics of the country (which has better or worse health, greater or lesser wealth, regardless of its population structure, etc.). Epidemiological measures to prevent transmission, mainly travel and mobility restrictions, proved to be much more efficient than having large hospital and medical resources. Inbound tourism turned out to be the variable that best predicts the number of infected (and, consequently, the number of deaths) happening in the different countries. Electricity consumption and degree of air pollution of a country (CO2 emissions, nitrous oxide and methane) are also capable of predicting, with great precision, the number of infections and deaths from Covid-19 in that country. Characteristics such as the area and population of a country also can predict, although to a lesser extent, the number of infected and dead. In contrast, a series of variables, which in principle would seem to have a greater influence on the evolution of Covid-19 (hospital bed density, Physicians per 1000 people, Researches in R & D, urban population, etc.), turned out to have very little ability to predict both the number of infected and the number of deaths from Covid-19. All this may explain why the countries that opted for social withdrawal policies since the start of the pandemic outbreak obtained better results.", "qid": 4, "docid": "iut1xj7k", "rank": 73, "score": 6.388599872589111}, {"content": "Title: COVID-19: Dying is Bad--Losing Life is Worse Content: Background: COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020. Methods: Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020. Results: COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US. Conclusion: Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states \"Prediction is difficult, especially when dealing with the future.\" We suggest that while dying is bad, losing life is even worse.", "qid": 4, "docid": "gtp01rna", "rank": 74, "score": 6.386099815368652}, {"content": "Title: Deaths from Covid-19: Who are the forgotten victims? Content: Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.", "qid": 4, "docid": "pn516wom", "rank": 75, "score": 6.384799957275391}, {"content": "Title: Forecasting the impact of the first wave of the COVID-19 pandemic on hospital demand and deaths for the USA and European Economic Area countries Content: Summary Background: Hospitals need to plan for the surge in demand in each state or region in the United States and the European Economic Area (EEA) due to the COVID-19 pandemic. Planners need forecasts of the most likely trajectory in the coming weeks and will want to plan for the higher values in the range of those forecasts. To date, forecasts of what is most likely to occur in the weeks ahead are not available for states in the USA or for all countries in the EEA. Methods: This study used data on confirmed COVID-19 deaths by day from local and national government websites and WHO. Data on hospital capacity and utilisation and observed COVID-19 utilisation data from select locations were obtained from publicly available sources and direct contributions of data from select local governments. We develop a mixed effects non-linear regression framework to estimate the trajectory of the cumulative and daily death rate as a function of the implementation of social distancing measures, supported by additional evidence from mobile phone data. An extended mixture model was used in data rich settings to capture asymmetric daily death patterns. Health service needs were forecast using a micro-simulation model that estimates hospital admissions, ICU admissions, length of stay, and ventilator need using available data on clinical practices in COVID-19 patients. We assume that those jurisdictions that have not implemented school closures, non-essential business closures, and stay at home orders will do so within twenty-one days. Findings: Compared to licensed capacity and average annual occupancy rates, excess demand in the USA from COVID-19 at the estimated peak of the epidemic (the end of the second week of April) is predicted to be 9,079 (95% UI 253-61,937) total beds and 9,356 (3,526-29,714) ICU beds. At the peak of the epidemic, ventilator use is predicted to be 16,545 (8,083-41,991). The corresponding numbers for EEA countries are 120,080 (119,183-121,107), 32,291 (32,157-32,425) and 28,973 (28,868-29,085) at a peak of April 6. The date of peak daily deaths varies from March 30 through May 12 by state in the USA and March 27 through May 4 by country in the EEA. We estimate that through the end of July, there will be 60,308 (34,063-140,381) deaths from COVID-19 in the USA and 143,088 (101,131-253,163) deaths in the EEA. Deaths from COVID-19 are estimated to drop below 0.3 per million between May 4 and June 29 by state in the USA and between May 4 and July 13 by country in the EEA. Timing of the peak need for hospital resource requirements varies considerably across states in the USA and across regions of Europe. Interpretation: In addition to a large number of deaths from COVID-19, the epidemic will place a load on health system resources well beyond the current capacity of hospitals in the USA and EEA to manage, especially for ICU care and ventilator use. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures within three weeks in all locations that have not done so already and maintenance of these measures throughout the epidemic, emphasising the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.", "qid": 4, "docid": "c1dy5vsn", "rank": 76, "score": 6.382699966430664}, {"content": "Title: Deaths from COVID-19 in healthcare workers in Italy\u2014What can we learn? Content: This letter examines healthcare worker deaths by category and medical speciality during the COVID-19 emergency in Italy, and underlines factors that may have contributed to the elevated number of fatalities among healthcare personnel. These data are now available because Italy was the first western country to be severely affected. These are matters for urgent discussion as development goes forward.", "qid": 4, "docid": "156es9v1", "rank": 77, "score": 6.356900215148926}, {"content": "Title: What could remdesivir data tell us about tackling COVID-19? Content: In the coming weeks, the world will get a sense of whether Gilead Sciences\u2019 remdesivir, an antiviral developed for Ebola, is useful against the novel coronavirus With the coronavirus pandemic spiraling\u2014during the week of March 30, worldwide infections crossed 900,000 and deaths exceeded 45,000\u2014initial results emerging from several late-stage studies will be under the microscope But infectious disease experts on the front lines warn that the data are unlikely to clearly answer the question of whether remdesivir works in COVID-19, the respiratory illness caused by the SARS-CoV-2 virus Those first tests are in the sickest, hardest-to-treat patients Moreover, antivirals don\u2019t have a great track record at taking down coronaviruses, which can be a little more sophisticated than your average RNA virus Still, some industry watchers hope the studies signal enough success to convince the US Food and Drug Administration to approve Gilead\u2019s experimental drug When a new infectious disease threatens", "qid": 4, "docid": "svp32re6", "rank": 78, "score": 6.343299865722656}, {"content": "Title: National age and coresidence patterns shape COVID-19 vulnerability Content: Based on harmonized census data from 81 countries, we estimate how age and coresidence patterns shape the vulnerability of countries' populations to outbreaks of coronavirus disease 2019 (COVID-19). We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age structures of European and North American countries increase their vulnerability to COVID-related deaths in general. The coresidence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of COVID-19. Southern European countries, which have aged populations and relatively high levels of intergenerational coresidence, are, all else equal, the most vulnerable to outbreaks of COVID-19. In a second step, we estimate to what extent avoiding primary infections for specific age groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational coresidence, such as France, whereas confining younger age groups can have a greater impact in countries with large and intergenerational households, such as Bangladesh.", "qid": 4, "docid": "gypm0p78", "rank": 79, "score": 6.3165998458862305}, {"content": "Title: National age and coresidence patterns shape COVID-19 vulnerability. Content: Based on harmonized census data from 81 countries, we estimate how age and coresidence patterns shape the vulnerability of countries' populations to outbreaks of coronavirus disease 2019 (COVID-19). We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age structures of European and North American countries increase their vulnerability to COVID-related deaths in general. The coresidence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of COVID-19. Southern European countries, which have aged populations and relatively high levels of intergenerational coresidence, are, all else equal, the most vulnerable to outbreaks of COVID-19. In a second step, we estimate to what extent avoiding primary infections for specific age groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational coresidence, such as France, whereas confining younger age groups can have a greater impact in countries with large and intergenerational households, such as Bangladesh.", "qid": 4, "docid": "iw4yv6l4", "rank": 80, "score": 6.316598892211914}, {"content": "Title: National age and co-residence patterns shape covid-19 vulnerability Content: Based on harmonized census data from 81 countries, we estimate how age and co-residence patterns shape the vulnerability of countries' populations to outbreaks of covid-19. We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age-structures of European and North American countries increase their vulnerability to covid-related deaths in general. The co-residence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of covid-19. Southern European countries, which have aged populations and relatively high levels of intergenerational co-residence are, all else equal, the most vulnerable to outbreaks of covid-19. In a second step, we estimate to what extent avoiding primary infections for specific age-groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational co-residence such as France, whereas confining younger age groups can have a greater impact in countries with large and inter-generational households such as Bangladesh.", "qid": 4, "docid": "tpxqj2do", "rank": 81, "score": 6.316597938537598}, {"content": "Title: What can trends in hospital deaths from COVID-19 tell us about the progress and peak of the pandemic? An analysis of death counts from England announced up to 25 April 2020 Content: Background. Reporting of daily hospital COVID-19 deaths in the UK are promoted by the government and scientific advisers alike as a key metric for assessing the progress in the control of the epidemic. These data, however, have certain limitations, among which one of the most significant concerns the fact that the daily totals span deaths that have occurred between 1 and 10 days or more in the past. Data and methods. We obtained daily data published published by NHS England up to and including April 25 in the form of Excel spreadsheets in which deaths counts are presented by date of death according to age and region. Simple descriptive analyses were conducted and presented in graphical and tabular form which were aimed at illustrating the biases inherent in focussing on daily counts regardless of when the deaths occurred. We then looked at how a less biased picture could be obtained by looking at trends in death counts stratifying by individual period of delay in days between occurrence of death and when the death was included in the daily announcement. Findings. The number of hospital COVID-19 deaths announced daily overestimates the maximum number of deaths actually occurring so far in the epidemic in the UK, and also obscures the pattern of decline in deaths. Taking account of reporting delays suggests that for England as a whole a peak in hospital COVID-19 deaths may have been reached on April 8 with a subsequent gradual decline suggested. The same peak is also seen among those aged 60-79 and 80+, although there is slightly shallower decline in the oldest age group (80+ years). Among those aged 40-59 years a later peak on April 11 is evident. London shows a peak on April 8 and a clearer and steeper pattern of subsequent decline compared to England as a whole. Interpretation. Analyses of mortality trends must take account of delay, and in communication with the public more emphasis should be placed on looking at trends based on deaths that occurred 5 or more days prior to the announcement day. The slightly weaker decline seen at age 80+ may reflect increased hospitalisation of people from care homes, whereas the later peak under the age of 60 years may reflect the higher proportions at these younger ages being admitted to critical care resulting in an extension of life of several days.", "qid": 4, "docid": "bfjefny3", "rank": 82, "score": 6.314000129699707}, {"content": "Title: Excess deaths hidden 100 days after the quarantine in Peru by COVID-19 Content: Objective: To make an estimate of the excess deaths caused by COVID-19 in the non-violent mortality of Peru, controlling for the effect of quarantine. Methods: Analysis of longitudinal data from the departments of Peru using official public information from the National Death Information System and the Ministry of Health of Peru. The analysis is performed between January 1, 2018 and June 23, 2020 (100 days of quarantine). The daily death rate per million inhabitants has been used. The days in which the departments were quarantined with a limit number of accumulated cases of COVID-19 were used to estimate the quarantine impact. Three limits were established for cases: less than 1, 10 and 100 cases. Result: In Peru, the daily death rate per million inhabitants decreased by -1.89 (95% CI: -2.70; -1.07) on quarantine days and without COVID-19 cases. When comparing this result with the total number of non-violent deaths, the excess deaths during the first 100 days of quarantine is 36,230. This estimate is 1.12 times the estimate with data from 2019 and 4.2 times the deaths officers by COVID-19. Conclusion: Quarantine reduced nonviolent deaths; however, they are overshadowed by the increase as a direct or indirect cause of the pandemic. Therefore, the difference between the number of current deaths and that of past years underestimates the real excess of deaths.", "qid": 4, "docid": "w57e1eu6", "rank": 83, "score": 6.3125}, {"content": "Title: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study Content: COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.", "qid": 4, "docid": "fbm3zoe2", "rank": 84, "score": 6.309700012207031}, {"content": "Title: Social-economic impact of COVID-19 pandemic on aesthetic centers in Greece Content: BACKGROUND: Epidemics are a major cause of health problems in developing countries, preventing the accumulation of human capital and economic growth. On the appearance of the pandemic of the new coronavirus COVID-19 worldwide, this survey was carried out in the 4th week of the occurrence of the cases in Greece. OBJECTIVES: The investigation was aimed at the social and economic impact caused by this COVID-19 pandemic and the state's decision to suspend the operation of businesses and stores in Greece. MATERIALS AND METHODS: One hundred and fifty-eight esthetic centers from various areas of Greece were participated in this study, and the questionnaires were sent electronically to the business owners. Statistical analyzes were conducted using Google Forms and the questionnaires analyzed through PSPP software. RESULTS: Based on their answers and the statistical analyzes, it was calculated the reduction of the monthly income for the first month of suspension of the operation of their companies. Additionally, social-related matters were examined as, how they experience this period, psychologically, financially, what problems they believe that they will face, and what changes in their work that could result from the pandemic. DISCUSSION: There is no similar study and experience for esthetic centers from a viral pandemic in literature. The suspension of operations provoked serious financial problems and significant psychological burden about what \"tomorrow will bring\" with returning to \"normalcy.\"", "qid": 4, "docid": "1cv7yvj1", "rank": 85, "score": 6.309599876403809}, {"content": "Title: Social\u2010economic impact of COVID\u201019 pandemic on aesthetic centers in Greece Content: BACKGROUND: Epidemics are a major cause of health problems in developing countries, preventing the accumulation of human capital and economic growth. On the appearance of the pandemic of the new coronavirus COVID\u201019 worldwide, this survey was carried out in the 4th week of the occurrence of the cases in Greece. OBJECTIVES: The investigation was aimed at the social and economic impact caused by this COVID\u201019 pandemic and the state's decision to suspend the operation of businesses and stores in Greece. MATERIALS AND METHODS: One hundred and fifth\u2010eight aesthetic centers from various areas of Greece were participated in this study, and the questionnaires were sent electronically to the business owners. Statistical analyzes were conducted using Google Forms and the questionnaires analyzed through PSPP software. RESULTS: Based on their answers and the statistical analyzes, it was calculated the reduction of the monthly income for the first month of suspension of the operation of their companies. Additionally, social related matters were examined as, how they experience this period, psychologically, financially, what problems they believe that they will face and what changes in their work that could result from the pandemic. DISCUSSION: There is no similar study and experience for aesthetic centers from a viral pandemic in literature. The suspension of operations provoked serious financial problems and significant psychological burden about what \u201ctomorrow will bring\u201d with returning to \u201cnormalcy\u201d.", "qid": 4, "docid": "9wlgmbit", "rank": 86, "score": 6.309598922729492}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 4, "docid": "ekxz577j", "rank": 87, "score": 6.2957000732421875}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015\u20132019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID\u201319 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 4, "docid": "t9qdiz7n", "rank": 88, "score": 6.295699119567871}, {"content": "Title: The COVID-19 (SARS-CoV-2) Uncertainty Tripod in Brazil: Assessments on model-based predictions with large under-reporting Content: The COVID-19 pandemic (SARS-CoV-2 virus) is the defying global health crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We propose an adapted Susceptible-Infected-Recovered (SIR) model which explicitly incorporates the under-reporting and the response of the population to public policies (such as confinement measures, widespread use of masks, etc) to cast short-term and long-term predictions. Large amounts of uncertainty could provide misleading models and predictions. In this paper, we discuss the role of uncertainty in these prediction, which is illustrated regarding three key aspects. First, assuming that the number of infected individuals is under-reported, we demonstrate an anticipation regarding the peak of infection. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic. Second, considering that the actual amount of deaths is larger than what is being register, then demonstrate the increase of the mortality rates. Third, when consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the effect of the\"COVID-19 under-reporting tripod\", i.e. the under-reporting in terms of infected individuals, of deaths and the true mortality rate. If two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates.", "qid": 4, "docid": "8cw3bjxh", "rank": 89, "score": 6.289400100708008}, {"content": "Title: Underreporting of death by COVID-19 in Brazil's second most populous state Content: The COVID-19 pandemic brings to light the reality of the Brazilian health system. The underreporting of COVID-19 deaths in the state of Minas Gerais (MG), where is concentrated the second largest population of the country, reveals government unpreparedness, as there is a low capacity of testing in the population, which prevents the real understanding of the general panorama of Sars-Cov-2 dissemination. The goals of this research are to analyze the causes of deaths in the different Brazilian government databases (ARPEN and SINAN) and to assess whether there are sub-records shown by the unexpected increase in the frequency of deaths from causes clinically similar to COVID-19. A descriptive and quantitative analysis of the number of COVID-19 deaths and similar causes was made in different databases. Ours results demonstrate that the different official sources had a discrepancy of 209.23% between these data referring to the same period. There was also a 648.61% increase in SARS deaths in 2020, when compared to the average of previous years. Finally, it was shown that there was an increase in the rate of pneumonia and respiratory insufficiency (RI) by 5.36% and 5.72%, respectively. In conclusion, there is an underreporting of COVID-19 deaths in MG due to the unexplained excess of SARS deaths, Respiratory insufficiency and pneumonia compared to previous years.", "qid": 4, "docid": "kusqyumn", "rank": 90, "score": 6.270899772644043}, {"content": "Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "qid": 4, "docid": "uc37poce", "rank": 91, "score": 6.269899845123291}, {"content": "Title: Non-Adherence Tree Analysis (NATA) - an adherence improvement framework: a COVID-19 case study Content: Poor adherence to medication is a global phenomenon that has received a significant amount of research attention yet remains largely unsolved. Medication non-adherence can blur drug efficacy results in clinical trials, lead to substantial financial losses, increase the risk of relapse and hospitalisation, or lead to death. The most common methods measuring adherence are post-treatment measures; that is, adherence is usually measured after the treatment has begun. What the authors are proposing in this multidisciplinary study is a technique for analysing the factors that can cause non-adherence before or during medication treatment. Fault Tree Analysis (FTA), allows system analysts to determine how combinations of simple faults of a system can propagate to cause a total system failure. Monte Carlo simulation is a mathematical algorithm that depends heavily on repeated random sampling to predict the behaviour of a system. In this study, the authors propose the use of Non-Adherence Tree Analysis (NATA), based on the FTA and Monte Carlo simulation techniques, to improve adherence. Firstly, the non-adherence factors of a medication treatment lifecycle are translated into what is referred to as a Non-Adherence Tree (NAT). Secondly, the NAT is coded into a format that is translated into the GoldSim software for performing dynamic system modelling and analysis using Monte Carlo. Finally, the GoldSim model is simulated and analysed to predict the behaviour of the NAT. This study produces a framework for improving adherence by analysing social and non-social adherence barriers. The results reveal that the biggest factor that could contribute to non-adherence to a COVID-19 treatment is a therapy-related factor (the side effects of the medication). This is closely followed by a condition-related factor (asymptomatic nature of the disease) then patient-related factors (forgetfulness and other causes). With this information, clinicians can implement relevant measures and allocate resources appropriately to minimise non-adherence.", "qid": 4, "docid": "x8b0ad7i", "rank": 92, "score": 6.267600059509277}, {"content": "Title: Forecasting the novel coronavirus COVID-19 Content: What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19.", "qid": 4, "docid": "d8eqifvv", "rank": 93, "score": 6.263500213623047}, {"content": "Title: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary. Content: The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.", "qid": 4, "docid": "7ksh8c5v", "rank": 94, "score": 6.2546000480651855}, {"content": "Title: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary Content: The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS: We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS: 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS: There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.", "qid": 4, "docid": "ndke01xy", "rank": 95, "score": 6.254599094390869}, {"content": "Title: Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) Content: The world is currently facing a serious SARS-CoV-2 infection pandemic. This virus is a new isolate of coronavirus, and the current infection crisis has surpassed the SARS and MERS epidemics that occurred in 2002 and 2013, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and spreading across more than 130 countries worldwide. The spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, thereby reiterating to the governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of the patients need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of the elderly, especially individuals who are older than 60 years of age, and have comorbidities, including hypertension, diabetes, and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow less susceptible and are not considered as a risk group. Therefore, in this review, we discuss some possible molecular and cellular mechanisms by virtue of which the elderly subjects may be more susceptible to severe COVID-19. Toward this, we raise two main points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe that these points are pivotal for a better understanding of the pathogenesis of severe COVID-19, and must be carefully addressed by physicians and scientists in the field.", "qid": 4, "docid": "59j1m2tm", "rank": 96, "score": 6.251399993896484}, {"content": "Title: QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review Content: Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.", "qid": 4, "docid": "e1otbzt3", "rank": 97, "score": 6.2256999015808105}, {"content": "Title: Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy Content: BACKGROUND: The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. METHODS: Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. RESULTS: The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. CONCLUSIONS: The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates.", "qid": 4, "docid": "4d3t6kas", "rank": 98, "score": 6.223100185394287}, {"content": "Title: Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy Content: Abstract Background The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. Methods Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. Results The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. Conclusions The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates.", "qid": 4, "docid": "ilnrvbpa", "rank": 99, "score": 6.223099231719971}, {"content": "Title: Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population Content: COVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.", "qid": 4, "docid": "afbvbgq5", "rank": 100, "score": 6.215400218963623}]}
{"query": "what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies?", "hits": [{"content": "Title: Remdesivir, the antiviral hope against SARS-CoV-2/ Remdesivir, la esperanza antiviral frente al SARS-CoV-2 Content: On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China) Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy However, studies and clinical trials in humans are required to know the result of their application in them", "qid": 5, "docid": "puc13jf1", "rank": 1, "score": 17.282400131225586}, {"content": "Title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs Content: COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 \u03bcM < IC50 < 10 \u03bcM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide \u2013 were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.", "qid": 5, "docid": "5f95gve3", "rank": 2, "score": 16.399999618530273}, {"content": "Title: Chloroquine paradox may cause more damage than help fight COVID-19 Content: Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.", "qid": 5, "docid": "86vzsrym", "rank": 3, "score": 16.278499603271484}, {"content": "Title: Chloroquine paradox may cause more damage than help fight COVID-19 Content: Abstract Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.", "qid": 5, "docid": "j9vmsfjw", "rank": 4, "score": 16.27849769592285}, {"content": "Title: Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study Content: Abstract Aims A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19. The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs\u2014Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)\u2014each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries. Main methods In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses. Key findings The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically. Significance The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA.", "qid": 5, "docid": "3pxc5wot", "rank": 5, "score": 16.175100326538086}, {"content": "Title: Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study Content: AIMS: A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19. The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs-Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)-each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries. MAIN METHODS: In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses. KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically. SIGNIFICANCE: The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA.", "qid": 5, "docid": "urpianz6", "rank": 6, "score": 16.175098419189453}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.", "qid": 5, "docid": "7h3rrea7", "rank": 7, "score": 16.017200469970703}, {"content": "Title: Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2? Content: New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of \u03b2-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.", "qid": 5, "docid": "g4bsu8jf", "rank": 8, "score": 15.981800079345703}, {"content": "Title: Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2? Content: New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of \u00df-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.", "qid": 5, "docid": "gxyk9fgj", "rank": 9, "score": 15.981799125671387}, {"content": "Title: A systematic review protocol of the antiviral activity of chloroquine and hydroxychloroquine against COVID-19. Content: Introduction: The recent outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), or COVID-19 with no approved medicines has led to global health threat. Currently, repositioning of old medicines seems the most responsible strategy for potential cure and prevention COVID-19. Hydroxychloroquine and chloroquine have shown promising efficacy against COVID-19 related pneumonia in clinical studies. However, the mode of drug action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection is not clear. This review aims to gather evidence on antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2, including in-vitro, animal studies, and studies in humans. Method: A structured search of five bibliographic databases namely; Medline, Web of Science, PubMed, Cochrane CENTRAL, and Google Scholar will be undertaken to retrieve studies that describe the antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2. No restrictions will be placed on publication date, but studies will be limited to only publications in English. Duplication of studies will be removed using EndNote reference manager. Three authors will screen the citations independently based on inclusion criteria. Data extraction and assessment of risk of bias will be done independently. Meta-analysis of selected studies will be done wherever suitable. Ethics and dissemination: Primary data collection will not be involved in this study, hence no need for formal ethical clearance. Findings from the study will be disseminated through a peer-reviewed publication and conference meeting. Trial registration number: https://doi.org/10.17605/OSF.IO/7DJMU", "qid": 5, "docid": "em98mikz", "rank": 10, "score": 15.898099899291992}, {"content": "Title: Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs Content: Licence: CC BY-NC-ND 4 0 Citation information: Arya, Rimanshee;Das, Amit;Prashar, Vishal;Kumar, Mukesh (2020): Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs ChemRxiv Preprint https://doi org/10 26434/chemrxiv 11860011 v2 The cases of 2019 novel coronavirus (SARS-CoV-2) infection have been continuously increasing ever since its outbreak in China last December Currently, there are no approved drugs to treat the infection In this scenario, there is a need to utilize the existing repertoire of FDA approved drugs to treat the disease The rational selection of these drugs could be made by testing their ability to inhibit any SARS-CoV-2 proteins essential for viral life-cycle We chose one such crucial viral protein, the papain-like protease (PLpro), to screen the FDA approved drugs in silico The homology model of the protease was built based on the SARS-coronavirus PLpro structure, and the drugs were docked in S3/S4 pockets of the active site of the enzyme In our docking studies, sixteen FDA approved drugs, including chloroquine and formoterol, was found to bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus File list (1) download file view on ChemRxiv 2019-nCoV_final_draft2_ChemRxiv pdf (1 15 MiB) Abstract The cases of 2019 novel coronavirus (SARS-CoV-2) infection have been continuously increasing ever since its outbreak in China last December Currently, there are no approved drugs to treat the infection In this scenario, there is a need to utilize the existing repertoire of FDA approved drugs to treat the disease The rational selection of these drugs could be made by testing their ability to inhibit any SARS-CoV-2 proteins essential for viral life-cycle We chose one such crucial viral protein, the papain-like protease (PLpro), to screen the FDA approved drugs in silico The homology model of the protease was built based on the SARS-coronavirus PLpro structure, and the drugs were docked in S3/S4 pockets of the active site of the enzyme In our docking studies, sixteen FDA approved drugs, including chloroquine and formoterol, was found to bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus", "qid": 5, "docid": "n2tckfjq", "rank": 11, "score": 15.847000122070312}, {"content": "Title: Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis Content: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibit in vitro activity against SARS-CoV-2. Nitazoxanide is an anthelmintic drug and its metabolite tizoxanide has been described to have broad antiviral activity against influenza and other coronaviruses. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide 90% effective concentration (EC90) against SARS-CoV-2. Methods: A whole-body PBPK model was constructed for oral administration of nitazoxanide and validated against available tizoxanide pharmacokinetic data for healthy individuals receiving single doses between 500 mg SARS-CoV-2 4000 mg with and without food. Additional validation against multiple-dose pharmacokinetic data when given with food was conducted. The validated model was then used to predict alternative doses expected to maintain tizoxanide plasma and lung concentrations over the reported nitazoxanide EC90 in >90% of the simulated population. Optimal design software PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. Results: The PBPK model was validated with AAFE values between 1.01 SARS-CoV-2 1.58 and a difference less than 2-fold between observed and simulated values for all the reported clinical doses. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food, to provide tizoxanide plasma and lung concentrations over the reported in vitro EC90 of nitazoxanide against SARS-CoV-2. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. Conclusion: The PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC90 for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection.", "qid": 5, "docid": "jvbehgb7", "rank": 12, "score": 15.706999778747559}, {"content": "Title: The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2 Content: The infection by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes major public health concern and economic burden. Although clinically approved drugs have been repurposed to treat individuals with 2019 Coronavirus disease (COVID-19), the lack of safety studies and limited efficiency as well jeopardize clinical benefits. Daclatasvir and sofosbuvir (SFV) are clinically approved direct-acting antivirals (DAA) against hepatitis C virus (HCV), with satisfactory safety profile. In the HCV replicative cycle, daclatasvir and SFV target the viral enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. These characteristics of the HCV and SARS-CoV-2 motivated us to further study the activity of daclatasvir and SFV against the new coronavirus. Daclatasvir consistently inhibited the production of infectious SARS-CoV-2 virus particles in Vero cells, in the hepatoma cell line HuH-7 and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 \u03bcM, respectively. Daclatasvir targeted early events during SARS-CoV-2 replication cycle and prevented the induction of IL-6 and TNF-\u03b1, inflammatory mediators associated with the cytokine storm typical of SARS-CoV-2 infection. Sofosbuvir, although inactive in Vero cells, displayed EC50 values of 6.2 and 9.5 \u03bcM in HuH-7 and Calu-3 cells, respectively. Our data point to additional antiviral candidates, in especial daclatasvir, among drugs overlooked for COVID-19, that could immediately enter clinical trials.", "qid": 5, "docid": "7w19xxlq", "rank": 13, "score": 15.689399719238281}, {"content": "Title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Content: The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.", "qid": 5, "docid": "l6l24pco", "rank": 14, "score": 15.685400009155273}, {"content": "Title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review Content: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Sa\u00fade (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.", "qid": 5, "docid": "8gmn0tae", "rank": 15, "score": 15.461899757385254}, {"content": "Title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review Content: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Sa\u00fade (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users.", "qid": 5, "docid": "qci7khki", "rank": 16, "score": 15.334199905395508}, {"content": "Title: Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach Content: BACKGROUND: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. METHODS: Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. RESULTS: Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. CONCLUSIONS: The anti-polymerase drugs predicted here\u2014CID123624208 and CID11687749\u2014may be considered for in vitro and in vivo clinical trials.", "qid": 5, "docid": "61nwk2sg", "rank": 17, "score": 15.317099571228027}, {"content": "Title: Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19 Content: The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue \u201cRecent Advances in Herpesviruses Research: What\u2019s in the Pipeline?\u201d aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.", "qid": 5, "docid": "dp4umo8l", "rank": 18, "score": 15.309100151062012}, {"content": "Title: Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19 Content: The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue \"Recent Advances in Herpesviruses Research: What's in the Pipeline?\" aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.", "qid": 5, "docid": "z1tw8nlm", "rank": 19, "score": 15.309099197387695}, {"content": "Title: Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. METHODS: We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. RESULTS: The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.", "qid": 5, "docid": "qnccsstb", "rank": 20, "score": 15.243300437927246}, {"content": "Title: Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo Content: SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.", "qid": 5, "docid": "jbc74lcu", "rank": 21, "score": 15.184200286865234}, {"content": "Title: Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor Content: SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (Mpro) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 \u00b1 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against Mpro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV. Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "5hkzm5pg", "rank": 22, "score": 15.128399848937988}, {"content": "Title: Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor. Content: SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (Mpro) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 \u00b1 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against Mpro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV. Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "eg8dih0o", "rank": 23, "score": 15.128398895263672}, {"content": "Title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Content: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be \u223c2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of \u223c6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found \u223c50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 \u2264 50 \u03bcM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 \u03bcM), Ciluprevir (20.77\u03bcM). Narlaprevir (IC50=1.10\u03bcM), and Telaprevir (15.25\u03bcM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.", "qid": 5, "docid": "slouuryl", "rank": 24, "score": 15.114399909973145}, {"content": "Title: SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries. Content: Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs.", "qid": 5, "docid": "ydywrk62", "rank": 25, "score": 15.091400146484375}, {"content": "Title: In-silico strategies for probing chloroquine based inhibitors against SARS-CoV-2 Content: The global health emergency of novel COVID-19 is due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently there are no approved drugs for the treatment of coronaviral disease (COVID-19), although some of the drugs have been tried. Chloroquine is being widely used in treatment of SARS-CoV-2 infection. Hydroxychloroquine, the derivative of Chloroquine shows better inhibition than Chloroquine and has in vitro activity against SARS-CoV-2 also used to treat COVID-19. To study the interactions of Chloroquine and derivatives of Chloroquine with SARS-CoV-2, series of computational approaches like pharmacophore model, molecular docking, MM_GBSA study and ADME property analysis are explored. The pharmacophore model and molecular docking study are used to explore the structural properties of the compounds and the ligand-receptor (PDB_ID: 6LU7) interactions respectively. MM_GBSA study gives the binding free energy of the protein-ligand complex and ADME property analysis explains the pharmacological property of the compounds. The resultant best molecule (CQD15) further subjected to molecular dynamics (MD) simulation study which explains the protein stability (RMSD), ligand properties as well as protein-ligand contacts. Outcomes of the present study conclude with the molecule CQD15 which shows better interactions for the inhibition of SARS-CoV-2 in comparison to Chloroquine and Hydroxychloroquine. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "eh65jhxb", "rank": 26, "score": 15.08240032196045}, {"content": "Title: In-silico strategies for probing chloroquine based inhibitors against SARS-CoV-2 Content: The global health emergency of novel COVID-19 is due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently there are no approved drugs for the treatment of coronaviral disease (COVID-19), although some of the drugs have been tried. Chloroquine is being widely used in treatment of SARS-CoV-2 infection. Hydroxychloroquine, the derivative of Chloroquine shows better inhibition than Chloroquine and has in vitro activity against SARS-CoV-2 also used to treat COVID-19. To study the interactions of Chloroquine and derivatives of Chloroquine with SARS-CoV-2, series of computational approaches like pharmacophore model, molecular docking, MM_GBSA study and ADME property analysis are explored. The pharmacophore model and molecular docking study are used to explore the structural properties of the compounds and the ligand-receptor (PDB_ID: 6LU7) interactions respectively. MM_GBSA study gives the binding free energy of the protein-ligand complex and ADME property analysis explains the pharmacological property of the compounds. The resultant best molecule (CQD15) further subjected to molecular dynamics (MD) simulation study which explains the protein stability (RMSD), ligand properties as well as protein-ligand contacts. Outcomes of the present study conclude with the molecule CQD15 which shows better interactions for the inhibition of SARS-CoV-2 in comparison to Chloroquine and Hydroxychloroquine.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "hqg5j51t", "rank": 27, "score": 15.082399368286133}, {"content": "Title: Elucidation on the Physicochemical Properties of Potential and Clinically Approved Antiviral Drugs: A Search for Effective Therapies against SARS-CoV-2 Infection Content: COVID-19 has been confirmed in millions of individuals worldwide, rendering it a global medical emergency In the absence of vaccines and the unavailability of effective drugs for the SARS-CoV-2 infection, vaccine development is being continuously explored and several antiviral compounds and immunotherapies are currently being investigated Given the high similarity in genetic identity between SARS-CoV and SARS-CoV-2, the present investigation identified the interaction between the physicochemical properties and the antiviral activity of different potential and clinically approved antiviral drugs against SARS-CoV using hierarchically weighted principal component analysis Representative drugs from the classes of neuraminidase inhibitors, reverse transcriptase inhibitors, protease inhibitors, nucleoside analogues, and other compounds with potential antiviral activity were examined The pharmacologic classification and the biological activity of the different antiviral drugs were described using indices, namely, rotatable bond count, molecular weight, heavy atom count, and molecular complexity (92 32% contribution rate) The physicochemical properties and inhibitory action against SARS-CoV-2 of lopinavir, chloroquine, ivermectin, and ciclesonide validated the adequacy of the current computational approach The findings of the present study provide additional information, although further investigation is warranted to identify potential targets and establish exact mechanisms, in the emergent search and design of antiviral drug candidates and their subsequent synthesis as effective therapies for COVID-19", "qid": 5, "docid": "s10iv1jg", "rank": 28, "score": 15.082099914550781}, {"content": "Title: Animal models for emerging coronavirus: progress and new insights Content: The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.", "qid": 5, "docid": "pld0clpd", "rank": 29, "score": 15.08180046081543}, {"content": "Title: Antiviral drug discovery against SARS-CoV. Content: Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.", "qid": 5, "docid": "1fy9edg3", "rank": 30, "score": 15.079299926757812}, {"content": "Title: Machine Learning Models Identify Inhibitors of SARS-CoV-2 Content: With the ongoing SARS-CoV-2 pandemic there is an urgent need for the discovery of a treatment for the coronavirus disease (COVID-19). Drug repurposing is one of the most rapid strategies for addressing this need and numerous compounds have been selected for in vitro testing by several groups already. These have led to a growing database of molecules with in vitro activity against the virus. Machine learning models can assist drug discovery through prediction of the best compounds based on previously published data. Herein we have implemented several machine learning methods to develop predictive models from recent SARS-CoV-2 in vitro inhibition data and used them to prioritize additional FDA approved compounds for in vitro testing selected from our in-house compound library. From the compounds predicted with a Bayesian machine learning model, CPI1062 and CPI1155 showed antiviral activity in HeLa-ACE2 cell-based assays and represent potential repurposing opportunities for COVID-19. This approach can be greatly expanded to exhaustively virtually screen available molecules with predicted activity against this virus as well as a prioritization tool for SARS-CoV-2 antiviral drug discovery programs. The very latest model for SARS-CoV-2 is available at www.assaycentral.org.", "qid": 5, "docid": "vfd0su0w", "rank": 31, "score": 15.078700065612793}, {"content": "Title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro Content: COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CLpro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root of Scutellaria baicalensis has been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts of S. baicalensis have exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredient compounds. We found that the ethanol extract of S. baicalensis inhibits SARS-CoV-2 3CLpro activity in vitro and the replication of SARS-CoV-2 in Vero cells with an EC50 of 0.74 \u03bcg/ml. Among the major components of S. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CLpro activity with an IC50 of 0.39 \u03bcM. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. Our study demonstrates that the extract of S. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors.", "qid": 5, "docid": "vy0mvzeb", "rank": 32, "score": 15.052300453186035}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.", "qid": 5, "docid": "l611eisi", "rank": 33, "score": 15.027299880981445}, {"content": "Title: Predicting inhibitors for SARS-CoV-2 RNA-dependent RNA polymerase using machine learning and virtual screening Content: Global coronavirus disease pandemic (COVID-19) caused by newly identified SARS- CoV-2 coronavirus continues to claim the lives of thousands of people worldwide. The unavailability of specific medications to treat COVID-19 has led to drug repositioning efforts using various approaches, including computational analyses. Such analyses mostly rely on molecular docking and require the 3D structure of the target protein to be available. In this study, we utilized a set of machine learning algorithms and trained them on a dataset of RNA-dependent RNA polymerase (RdRp) inhibitors to run inference analyses on antiviral and anti-inflammatory drugs solely based on the ligand information. We also performed virtual screening analysis of the drug candidates predicted by machine learning models and docked them against the active site of SARS- CoV-2 RdRp, a key component of the virus replication machinery. Based on the ligand information of RdRp inhibitors, the machine learning models were able to identify candidates such as remdesivir and baloxavir marboxil, molecules with documented activity against RdRp of the novel coronavirus. Among the other identified drug candidates were beclabuvir, a non-nucleoside inhibitor of the hepatitis C virus (HCV) RdRp enzyme, and HCV protease inhibitors paritaprevir and faldaprevir. Further analysis of these candidates using molecular docking against the SARS-CoV-2 RdRp revealed low binding energies against the enzyme active site. Our approach also identified anti-inflammatory drugs lupeol, lifitegrast, antrafenine, betulinic acid, and ursolic acid to have potential activity against SARS-CoV-2 RdRp. We propose that the results of this study are considered for further validation as potential therapeutic options against COVID-19.", "qid": 5, "docid": "0s1vgu85", "rank": 34, "score": 15.009200096130371}, {"content": "Title: Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review Content: Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.", "qid": 5, "docid": "a179xi5p", "rank": 35, "score": 14.984600067138672}, {"content": "Title: Revisiting potential druggable targets against SARS\u2010CoV\u20102 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review Content: Coronavirus disease\u201019 (COVID\u201019), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID\u201019 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS\u2010CoV\u20102. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target\u2010based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti\u2010SARS\u2010CoV\u20102 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS\u2010CoV\u20102 infection.", "qid": 5, "docid": "xkoilncd", "rank": 36, "score": 14.984599113464355}, {"content": "Title: Towards a pharmacochemical hypothesis of the prophylaxis of SARS-CoV-2 by psychoactive substances Content: An increasing body of evidence suggests a protective effect of some psychoactive substances against SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus type 2). Recent findings suggest that patients with psychiatric disorders are less affected by SARS-CoV-2 than their caregivers, which may seem surprising given some of the frequent risk factors for an unfavorable course of the disease (e.g., obesity, diabetes, cardiovascular and pulmonary diseases). We propose here a mixed pharmacoepidemiological and pharmacochemical hypothesis to explain these findings. A number of psychotropic drugs exhibit activities against coronaviruses (Middle East Respiratory Syndrome coronavirus (MERS-CoV), the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and the Infectious Bronchitis Virus (IBV)) and have been put forward as potentially anti-SARS-CoV-2. These treatments include numerous mee-too drugs (chemically and pharmacologically linked to those which have demonstrated anti-SARS-CoV-2 efficacy) which are frequently prescribed in psychiatric settings. Taken alone or in polypharmacy, these drugs could have a prophylactic anti-SARS-CoV-2 effect, explaining the unexpectedly low proportion of patients with psychiatric disorders and COVID-19. Associated factors such as nicotine can also be considered in the context of a broad chemoprophylactic hypothesis in patients with psychiatric disorders taking different psychoactive substances.", "qid": 5, "docid": "ld9t64xk", "rank": 37, "score": 14.90410041809082}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "aqge7xuu", "rank": 38, "score": 14.889699935913086}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "xui8cfzv", "rank": 39, "score": 14.88969898223877}, {"content": "Title: Why Are Lopinavir and Ritonavir Effective against the Newly Emerged Coronavirus 2019? Atomistic Insights into the Inhibitory Mechanisms Content: Since the emergence of a novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, neither a specific vaccine nor an antiviral drug against SARS-CoV-2 has become available. However, a combination of two HIV-1 protease inhibitors, lopinavir and ritonavir, has been found to be effective against SARS-CoV, and both drugs could bind well to the SARS-CoV 3C-like protease (SARS-CoV 3CLpro). In this work, molecular complexation between each inhibitor and SARS-CoV-2 3CLpro was studied using all-atom molecular dynamics simulations, free energy calculations, and pair interaction energy analyses based on MM/PB(GB)SA and FMO-MP2/PCM/6-31G* methods. Both anti-HIV drugs interacted well with the residues at the active site of SARS-CoV-2 3CLpro. Ritonavir showed a somewhat higher number atomic contacts, a somewhat higher binding efficiency, and a somewhat higher number of key binding residues compared to lopinavir, which correspond with the slightly lower water accessibility at the 3CLpro active site. In addition, only ritonavir could interact with the oxyanion hole residues N142 and G143 via the formation of two hydrogen bonds. The interactions in terms of electrostatics, dispersion, and charge transfer played an important role in the drug binding. The obtained results demonstrated how repurposed anti-HIV drugs could be used to combat COVID-19.", "qid": 5, "docid": "bxw5pnjy", "rank": 40, "score": 14.883600234985352}, {"content": "Title: An approach towards development of monoclonal IgY antibodies against SARS CoV-2 spike protein (S) using phage display method: A review Content: The present state of diagnostic and therapeutic developmental race for vaccines against the SARS CoV-2 (nCOVID-19) focuses on prevention and control of this global pandemic which also represents a critical challenge to the global health community. Although development of novel vaccines can prevent the SARS CoV-2 infections, it is still impeded by several other factors and therefore novel approaches towards treatment and management of this disease is the urgent need. Passive immunotherapy plays a vital role as a possible alternative to meet this challenge and among various antibody sources, chicken egg yolk antibodies (IgY) can be used as an alternative to mammalian antibodies which have been previously studied against SARS CoV outbreak in China. In this review, we discuss the strategies for the use of chicken egg yolk (IgY) antibodies in the development of rapid diagnosis and immunotherapy against SARS CoV-2. Also, IgY antibodies have previously been used against various respiratory bacterial and viral infections in humans and animals. Compared to mammalian antibodies (IgG), chicken egg yolk antibodies (IgY) have greater binding affinity to specific antigens, ease of extraction and lower production costs, hence possessing remarkable pathogen-neutralizing activity of pathogens in respiratory and lungs. We provide an overall importance for the use of monoclonal chicken egg yolk antibodies (IgY) using phage display method describing their potential passive immunotherapeutic application for the treatment and prevention of SARS CoV-2 infection which is simple, fast and safe way of approach for treating patients effectively.", "qid": 5, "docid": "wpurd2gu", "rank": 41, "score": 14.873299598693848}, {"content": "Title: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 Content: The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.", "qid": 5, "docid": "qebbkr6d", "rank": 42, "score": 14.872200012207031}, {"content": "Title: Medication for COVID-19\u2014an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with ClinicalTrials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARS-CoV-2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 5, "docid": "vyeescn8", "rank": 43, "score": 14.8503999710083}, {"content": "Title: Chemical-informatics approach to COVID-19 drug discovery: Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease (PLpro) inhibitors Content: World Health Organization characterized novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) as world pandemic. This infection has been spreading alarmingly by causing huge social and economic disruption. In order to response quickly, the inhibitors already designed against different targets of previous human coronavirus infections will be a great starting point for anti-SARS-CoV-2 inhibitors. In this study, our approach integrates different ligand based drug design strategies of some in-house chemicals. The study design was composed of some major aspects: (a) classification QSAR based data mining of diverse SARS-CoV papain-like protease (PLpro) inhibitors, (b) QSAR based virtual screening (VS) to identify in-house molecules that could be effective against putative target SARS-CoV PLpro and (c) finally validation of hits through receptor-ligand interaction analysis. This approach could be used to aid in the process of COVID-19 drug discovery. It will introduce key concepts, set the stage for QSAR based screening of active molecules against putative SARS-CoV-2 PLpro enzyme. Moreover, the QSAR models reported here would be of further use to screen large database. This study will assume that the reader is approaching the field of QSAR and molecular docking based drug discovery against SARS-CoV-2 PLpro with little prior knowledge. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "uhwe6xk1", "rank": 44, "score": 14.80739974975586}, {"content": "Title: Chemical-informatics approach to COVID-19 drug discovery: Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease (PLpro) inhibitors Content: World Health Organization characterized novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) as world pandemic. This infection has been spreading alarmingly by causing huge social and economic disruption. In order to response quickly, the inhibitors already designed against different targets of previous human coronavirus infections will be a great starting point for anti-SARS-CoV-2 inhibitors. In this study, our approach integrates different ligand based drug design strategies of some in-house chemicals. The study design was composed of some major aspects: (a) classification QSAR based data mining of diverse SARS-CoV papain-like protease (PLpro) inhibitors, (b) QSAR based virtual screening (VS) to identify in-house molecules that could be effective against putative target SARS-CoV PLpro and (c) finally validation of hits through receptor-ligand interaction analysis. This approach could be used to aid in the process of COVID-19 drug discovery. It will introduce key concepts, set the stage for QSAR based screening of active molecules against putative SARS-CoV-2 PLpro enzyme. Moreover, the QSAR models reported here would be of further use to screen large database. This study will assume that the reader is approaching the field of QSAR and molecular docking based drug discovery against SARS-CoV-2 PLpro with little prior knowledge.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "xjwwrc06", "rank": 45, "score": 14.807398796081543}, {"content": "Title: [Comment] Treatment strategies to fight the new coronavirus SARS-CoV-2: A challenge for a Rubik's Cube solver Content: SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.", "qid": 5, "docid": "g8bu2ene", "rank": 46, "score": 14.798199653625488}, {"content": "Title: Why Are Lopinavir and Ritonavir Effective against the Newly Emerged Coronavirus 2019? Atomistic Insights into the Inhibitory Mechanisms Content: [Image: see text] Since the emergence of a novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, neither a specific vaccine nor an antiviral drug against SARS-CoV-2 has become available. However, a combination of two HIV-1 protease inhibitors, lopinavir and ritonavir, has been found to be effective against SARS-CoV, and both drugs could bind well to the SARS-CoV 3C-like protease (SARS-CoV 3CL(pro)). In this work, molecular complexation between each inhibitor and SARS-CoV-2 3CL(pro) was studied using all-atom molecular dynamics simulations, free energy calculations, and pair interaction energy analyses based on MM/PB(GB)SA and FMO-MP2/PCM/6-31G* methods. Both anti-HIV drugs interacted well with the residues at the active site of SARS-CoV-2 3CL(pro). Ritonavir showed a somewhat higher number atomic contacts, a somewhat higher binding efficiency, and a somewhat higher number of key binding residues compared to lopinavir, which correspond with the slightly lower water accessibility at the 3CL(pro) active site. In addition, only ritonavir could interact with the oxyanion hole residues N142 and G143 via the formation of two hydrogen bonds. The interactions in terms of electrostatics, dispersion, and charge transfer played an important role in the drug binding. The obtained results demonstrated how repurposed anti-HIV drugs could be used to combat COVID-19.", "qid": 5, "docid": "7ew6lrvh", "rank": 47, "score": 14.745699882507324}, {"content": "Title: Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor Content: The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genus Betacoronavirus. Although few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections in coming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score \u2212 141.36 and \u2212 148.621 kcal/mole) and ACE2 receptor (MolDock score \u2212 142.647 and \u2212 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood\u2013brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.", "qid": 5, "docid": "0qwveb68", "rank": 48, "score": 14.739299774169922}, {"content": "Title: Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections Content: The need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga\u00ae, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection. One Sentence Summary An analogue of Cerdelga\u00ae, an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.", "qid": 5, "docid": "2ejg2ngh", "rank": 49, "score": 14.7322998046875}, {"content": "Title: A pharmacological perspective of Chloroquine in SARS-CoV-2 infection Content: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria; in addition, their antiviral properties have been previously studied, including in coronaviruses, where evidence of efficacy has been found. The safety of CQ and HCQ has been studied for over 50 years. In the current race against time triggered by the SARS-CoV-2 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ; these could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low MW heparin, aimed at preventing ARDS-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however, recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. The review that we here provide also reexamines the real information provided by some of the published alarming reports although concluding that cardiac toxicity should in any case be stringently monitored with patients with CQ/HCQ.", "qid": 5, "docid": "wgm26pla", "rank": 50, "score": 14.696700096130371}, {"content": "Title: Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 Content: There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation.", "qid": 5, "docid": "hsc2x36j", "rank": 51, "score": 14.675999641418457}, {"content": "Title: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication. Content: The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 \u03bcg/mL) or nafamostat (0.01-1 \u03bcg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.", "qid": 5, "docid": "1a6guo10", "rank": 52, "score": 14.671299934387207}, {"content": "Title: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication Content: The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 \u00b5g/mL) or nafamostat (0.01-1 \u00b5g/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.", "qid": 5, "docid": "npp1y2ay", "rank": 53, "score": 14.67129898071289}, {"content": "Title: In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19 Content: The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.", "qid": 5, "docid": "w9mij6c6", "rank": 54, "score": 14.670000076293945}, {"content": "Title: Possibility of HIV-1 protease inhibitors-clinical trial drugs as repurposed drugs for SARS-CoV-2 main protease: a molecular docking, molecular dynamics and binding free energy simulation study Content: Initially, the SARS-CoV-2 virus was emerged from Wuhan, China and rapidly spreading across the world and urges the scientific community to develop antiviral therapeutic agents. Among several strategies, drug repurposing will help to react immediately to overcome the COVID-19 pandemic. In the present study, we have chosen two clinical trial drugs against HIV-1 protease namely, TMB607 and TMC310911 to use as the inhibitors of SARS-CoV-2 main protease (Mpro) enzyme. To make use of these two inhibitors as the repurposed drugs for COVID-19, it is essential to know the molecular basis of the binding mechanism of these two molecules with the SARS-CoV-2 Mpro. To understand the binding mechanism, we have performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations against the SARS-CoV-2 Mpro. The docking results indicate that both molecules form intermolecular interactions with the active site amino acids of Mpro enzyme. However, during the MD simulations, TMB607 forms strong interaction with the key amino acids of Mpro, and remains intact. The RMSD and RMSF values of both complexes were stable throughout the MD simulations. The MM-GBSA binding free energy values of both complexes are -43.7 and -34.9 kcal/mol, respectively. This in silico study proves that the TMB607 molecule binds strongly with the SARS-CoV-2 Mpro enzyme and it may be suitable for the drug repurposing of COVID-19 and further drug designing. Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "19aeuzer", "rank": 55, "score": 14.656900405883789}, {"content": "Title: Possibility of HIV-1 protease inhibitors-clinical trial drugs as repurposed drugs for SARS-CoV-2 main protease: a molecular docking, molecular dynamics and binding free energy simulation study. Content: Initially, the SARS-CoV-2 virus was emerged from Wuhan, China and rapidly spreading across the world and urges the scientific community to develop antiviral therapeutic agents. Among several strategies, drug repurposing will help to react immediately to overcome the COVID-19 pandemic. In the present study, we have chosen two clinical trial drugs against HIV-1 protease namely, TMB607 and TMC310911 to use as the inhibitors of SARS-CoV-2 main protease (Mpro) enzyme. To make use of these two inhibitors as the repurposed drugs for COVID-19, it is essential to know the molecular basis of the binding mechanism of these two molecules with the SARS-CoV-2 Mpro. To understand the binding mechanism, we have performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations against the SARS-CoV-2 Mpro. The docking results indicate that both molecules form intermolecular interactions with the active site amino acids of Mpro enzyme. However, during the MD simulations, TMB607 forms strong interaction with the key amino acids of Mpro, and remains intact. The RMSD and RMSF values of both complexes were stable throughout the MD simulations. The MM-GBSA binding free energy values of both complexes are -43.7 and -34.9 kcal/mol, respectively. This in silico study proves that the TMB607 molecule binds strongly with the SARS-CoV-2 Mpro enzyme and it may be suitable for the drug repurposing of COVID-19 and further drug designing. Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "2v4izbiq", "rank": 56, "score": 14.656899452209473}, {"content": "Title: Primum non nocere \u2013 Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)? Content: Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.", "qid": 5, "docid": "u87lx38h", "rank": 57, "score": 14.647299766540527}, {"content": "Title: Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach. Content: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.", "qid": 5, "docid": "9bhp3lph", "rank": 58, "score": 14.629799842834473}, {"content": "Title: Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach Content: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "cvavb7j1", "rank": 59, "score": 14.629798889160156}, {"content": "Title: Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the \u03b2-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2.", "qid": 5, "docid": "dqxfcwyu", "rank": 60, "score": 14.61620044708252}, {"content": "Title: Artificial intelligence approach fighting COVID-19 with repurposing drugs Content: BACKGROUND: The ongoing COVID-19 pandemic has caused more than 193,825 deaths during the past few months. A quick-to-be-identified cure for the disease will be a therapeutic medicine that has prior use experiences in patients in order to resolve the current pandemic situation before it could become worsening. Artificial intelligence (AI) technology is hereby applied to identify the marketed drugs with potential for treating COVID-19. MATERIAL AND METHODS: An AI platform was established to identify potential old drugs with anti-coronavirus activities by using two different learning databases; one consisted of the compounds reported or proven active against SARS-CoV, SARS-CoV-2, human immunodeficiency virus, influenza virus, and the other one containing the known 3C-like protease inhibitors. All AI predicted drugs were then tested for activities against a feline coronavirus in in vitro cell-based assay. These assay results were feedbacks to the AI system for relearning and thus to generate a modified AI model to search for old drugs again. RESULTS: After a few runs of AI learning and prediction processes, the AI system identified 80 marketed drugs with potential. Among them, 8 drugs (bedaquiline, brequinar, celecoxib, clofazimine, conivaptan, gemcitabine, tolcapone, and vismodegib) showed in vitro activities against the proliferation of a feline infectious peritonitis (FIP) virus in Fcwf-4 cells. In addition, 5 other drugs (boceprevir, chloroquine, homoharringtonine, tilorone, and salinomycin) were also found active during the exercises of AI approaches. CONCLUSION: Having taken advantages of AI, we identified old drugs with activities against FIP coronavirus. Further studies are underway to demonstrate their activities against SARS-CoV-2 in vitro and in vivo at clinically achievable concentrations and doses. With prior use experiences in patients, these old drugs if proven active against SARS-CoV-2 can readily be applied for fighting COVID-19 pandemic.", "qid": 5, "docid": "fhmr1og4", "rank": 61, "score": 14.60569953918457}, {"content": "Title: Artificial intelligence approach fighting COVID-19 with repurposing drugs Content: Background: The ongoing COVID-19 pandemic has caused more than 193,825 deaths during the past few months. A quick-to-be-identified cure for the disease will be a therapeutic medicine that has prior use experiences in patients in order to resolve the current pandemic situation before it could become worsening. Artificial intelligence (AI) technology is hereby applied to identify the marketed drugs with potential for treating COVID-19. Material and methods: An AI platform was established to identify potential old drugs with anti-coronavirus activities by using two different learning databases; one consisted of the compounds reported or proven active against SARS-CoV, SARS-CoV-2, human immunodeficiency virus, influenza virus, and the other one containing the known 3C-like protease inhibitors. All AI predicted drugs were then tested for activities against a feline coronavirus in in vitro cell-based assay. These assay results were feedbacks to the AI system for relearning and thus to generate a modified AI model to search for old drugs again. Results: After a few runs of AI learning and prediction processes, the AI system identified 80 marketed drugs with potential. Among them, 8 drugs (bedaquiline, brequinar, celecoxib, clofazimine, conivaptan, gemcitabine, tolcapone, and vismodegib) showed in vitro activities against the proliferation of a feline infectious peritonitis (FIP) virus in Fcwf-4 cells. In addition, 5 other drugs (boceprevir, chloroquine, homoharringtonine, tilorone, and salinomycin) were also found active during the exercises of AI approaches. Conclusion: Having taken advantages of AI, we identified old drugs with activities against FIP coronavirus. Further studies are underway to demonstrate their activities against SARS-CoV-2 in vitro and in vivo at clinically achievable concentrations and doses. With prior use experiences in patients, these old drugs if proven active against SARS-CoV-2 can readily be applied for fighting COVID-19 pandemic.", "qid": 5, "docid": "wrzh32lh", "rank": 62, "score": 14.605698585510254}, {"content": "Title: Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2. Content: The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation..", "qid": 5, "docid": "hchioraj", "rank": 63, "score": 14.587599754333496}, {"content": "Title: An enzyme-based immunodetection assay to quantify SARS-CoV-2 infection Content: SARS-CoV-2 is a novel pandemic coronavirus that caused a global health and economic crisis. The development of efficient drugs and vaccines against COVID-19 requires detailed knowledge about SARS-CoV-2 biology. Several techniques to detect SARS-CoV-2 infection have been established, mainly based on counting infected cells by staining plaques or foci, or by quantifying the viral genome by PCR. These methods are laborious, time-consuming and expensive and therefore not suitable for a high sample throughput or rapid diagnostics. We here report a novel enzyme-based immunodetection assay that directly quantifies the amount of de novo synthesized viral spike protein within fixed and permeabilized cells. This in-cell ELISA enables a rapid and quantitative detection of SARS-CoV-2 infection in microtiter format, regardless of the virus isolate or target cell culture. It follows the established method of performing ELISA assays and does not require expensive instrumentation. Utilization of the in-cell ELISA allows to e.g. determine TCID50 of virus stocks, antiviral efficiencies (IC50 values) of drugs or neutralizing activity of sera. Thus, the in-cell spike ELISA represents a promising alternative to study SARS-CoV-2 infection and inhibition and may facilitate future research. Highlights Determination of SARS-CoV-2 infection by enzymatically quantifying the expression of viral spike protein in bulk cell cultures Targeting a highly conserved region in the S2 subunit of the S protein allows broad detection of several SARS-CoV-2 isolates in different cell lines Screening of antivirals in microtiter format and determining the antiviral activity as inhibitory concentrations 50 (IC50)", "qid": 5, "docid": "ew78trl9", "rank": 64, "score": 14.570699691772461}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 5, "docid": "3sepefqa", "rank": 65, "score": 14.5649995803833}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials. Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 5, "docid": "oa8vzf02", "rank": 66, "score": 14.564998626708984}, {"content": "Title: Potentially repurposable drugs for COVID-19 identified from SARS-CoV-2 Host Protein Interactome Content: We previously presented the protein-protein interaction network - the \u2018HoP\u2019 or the host protein interactome - of 332 host proteins that were identified to interact with 27 nCoV19 viral proteins by Gordon et al. Here, we studied drugs targeting the proteins in this interactome to identify whether any of them may potentially be repurposable against SARS-CoV-2. We studied each of the drugs using the BaseSpace Correlation Engine and identified those that induce gene expression profiles negatively correlated with SARS-associated expression profile. This analysis resulted in 20 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for SARS (viral infection versus normal). These included drugs that were already being tested for their clinical activity against SARS-CoV-2, those with proven activity against SARS-CoV/MERS-CoV, broad-spectrum antiviral drugs, and those identified/prioritized by other computational re-purposing studies. In summary, our integrated computational analysis of the HoP interactome in conjunction with drug-induced transcriptomic data resulted in drugs that may be repurposable for COVID-19.", "qid": 5, "docid": "yv2gjjzg", "rank": 67, "score": 14.532099723815918}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 5, "docid": "1cph1uij", "rank": 68, "score": 14.50469970703125}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 5, "docid": "jxbch44o", "rank": 69, "score": 14.504698753356934}, {"content": "Title: Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements Content: The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.", "qid": 5, "docid": "0wh7x410", "rank": 70, "score": 14.499899864196777}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "rvzgut4w", "rank": 71, "score": 14.48639965057373}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5\u20139 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]", "qid": 5, "docid": "4178ui2c", "rank": 72, "score": 14.466099739074707}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.", "qid": 5, "docid": "r0znh1bi", "rank": 73, "score": 14.46609878540039}, {"content": "Title: Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach Content: The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.", "qid": 5, "docid": "1evug4fr", "rank": 74, "score": 14.46560001373291}, {"content": "Title: Montelukast drug activity and potential against SARS-CoV-2. Content: COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "qid": 5, "docid": "ntozf7ba", "rank": 75, "score": 14.455300331115723}, {"content": "Title: Montelukast drug activity and potential against SARS-CoV-2 Content: COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "qid": 5, "docid": "w3ido97l", "rank": 76, "score": 14.455299377441406}, {"content": "Title: Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion. Content: Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. The efficiency of human ACE2 to support WIV1 infectious entry is similar to that of mild SARS-CoV isolate GD03 and two civet cat SL-CoVs, but approximately 50% of that to SARS-CoV Tor2. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to activate spike-mediated membrane fusion and partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B, an antimycotic drug commonly used in clinic for patients with severe fungal infections, could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).", "qid": 5, "docid": "vx0dl0iv", "rank": 77, "score": 14.44950008392334}, {"content": "Title: Evaluating the potential of different inhibitors on RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2: A molecular modeling approach Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has already affected 2883603 and killed 198842 people, as of April 27, 2020. Because there is no specific therapeutic drug, drug repurposing has been proposed. RNA-dependent RNA polymerase (RdRp) is a promising drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control its replication, and several compounds have been suggested. The present study predicts relative efficacies of thirty known or repurposed compounds in inhibiting the RdRp. METHODS: The three-dimensional structure of the target enzyme was loaded into Molegro virtual docker software, followed by chemical structures of the test compounds. The docking was performed between the compounds and the active site of the enzyme to determine docking scores, and the energy liberated when the two dock. Thus, docking scores signify the affinity of ligand(s) with the active site of enzyme(s) and thus its inhibitory potential. RESULTS: Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp. Among all compounds, chlorhexidine was predicted as the most potent inhibitor. Furthermore, the results predict the relative efficacy of different drugs as inhibitors of the drug target. CONCLUSION: While the study identifies several compounds as inhibitors of RdRp of SARS-CoV-2, the prediction of their relative efficacies may be useful in future studies. While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site. Thus, based on the findings, we recommend in vitro and in vivo studies and clinical trials to determine their effectiveness against COVID-19.", "qid": 5, "docid": "9ikgkpds", "rank": 78, "score": 14.446200370788574}, {"content": "Title: A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex Content: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended in the characterization of the SARS-CoV replication/transcription machinery. Until recently, a pure and highly active preparation of SARS-CoV recombinant RNA synthesis machinery was not available, impeding target-based high throughput screening of drug candidates against this viral family. The current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic revealed a new pathogen whose RNA synthesis machinery is highly (>96% aa identity) homologous to SARS-CoV. This phylogenetic relatedness highlights the potential use of conserved replication enzymes to discover inhibitors against this significant pathogen, which in turn, contributes to scientific preparedness against emerging viruses. Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. The screening of a small (1,520 compounds) chemical library of FDA-approved drugs demonstrates the robustness of our assay and will allow to speed-up drug repositioning or novel drug discovery against the SARS-CoV-2. Principle of SARS-CoV RNA synthesis detection by a fluorescence-based high throughput screening assay Highlights - A new SARS-CoV non radioactive RNA polymerase assay is described - The robotized assay is suitable to identify RdRp inhibitors based on HTS", "qid": 5, "docid": "gytebbua", "rank": 79, "score": 14.437399864196777}, {"content": "Title: Animal models of mechanisms of SARS\u2010CoV\u20102 infection and COVID\u201019 pathology Content: The coronavirus disease 2019 (COVID\u201019) pandemic caused by SARS\u2010CoV\u20102 infections has led to substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS\u2010CoV\u20102 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID\u201019. At the time of writing, in vivo studies of SARS\u2010CoV\u20102 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partially model the mechanisms implicated in human severe COVID\u201019. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID\u201019. These models need to recapitulate key mechanisms of COVID\u201019 severe acute respiratory distress syndrome and reproduce the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS\u2010CoV\u20102 infection and COVID\u201019\u2010related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID\u201019 pathogenesis and for assessing potential treatments.", "qid": 5, "docid": "bvociyg2", "rank": 80, "score": 14.435700416564941}, {"content": "Title: Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology Content: The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 infections has led to substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS-CoV-2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID-19. At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partially model the mechanisms implicated in human severe COVID-19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID-19. These models need to recapitulate key mechanisms of COVID-19 severe acute respiratory distress syndrome and reproduce the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS-CoV-2 infection and COVID-19-related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID-19 pathogenesis and for assessing potential treatments.", "qid": 5, "docid": "zw2boiyo", "rank": 81, "score": 14.435699462890625}, {"content": "Title: Antiviral activities of mycophenolic acid and IMD\u20100354 against SARS\u2010CoV\u20102 Content: In this study, anti\u2010SARS\u2010CoV\u20102 activity of mycophenolic acid (MPA) and IMD\u20100354 was analyzed, these compounds were chosen based on their antiviral activities against other coronaviruses. Since they also inhibit Dengue virus (DENV) infection, other anti\u2010DENV compounds/drugs were also assessed. Using SARS\u2010CoV\u20102\u2010infected VeroE6/TMPRSS2 cells, MPA and IMD\u20100354, but not other anti\u2010DENV compounds/drugs, showed significant anti\u2010SARS\u2010CoV\u20102 activity. Although MPA reduced the viral RNA level by only ~100\u2010fold, its EC(50) was as low as 0.87\u00b5M, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets coronaviral papain\u2010like protease and its study would be useful in the development of novel anti\u2010SARS\u2010CoV\u20102 drugs. This article is protected by copyright. All rights reserved.", "qid": 5, "docid": "78zch9yh", "rank": 82, "score": 14.421799659729004}, {"content": "Title: Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2 Content: In this study, anti-SARS-CoV-2 activity of mycophenolic acid (MPA) and IMD-0354 was analyzed, these compounds were chosen based on their antiviral activities against other coronaviruses. Since they also inhibit Dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. Using SARS-CoV-2-infected VeroE6/TMPRSS2 cells, MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only ~100-fold, its EC50 was as low as 0.87\u00b5M, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets coronaviral papain-like protease and its study would be useful in the development of novel anti-SARS-CoV-2 drugs. This article is protected by copyright. All rights reserved.", "qid": 5, "docid": "fcxjt7qf", "rank": 83, "score": 14.421798706054688}, {"content": "Title: Identification of potential drugs against SARS-CoV-2 non-structural protein 1 (nsp1). Content: Non-structural protein 1 (nsp1) is found in all Betacoronavirus genus, an important viral group that causes severe respiratory human diseases. This protein has significant role in pathogenesis and it is considered a probably major virulence factor. As it is absent in humans, it becomes an interesting target of study, especially when it comes to the rational search for drugs, since it increases the specificity of the target and reduces possible adverse effects that may be caused to the patient. Using approaches in silico we seek to study the behavior of nsp1 in solution to obtain its most stable conformation and find possible drugs with affinity to all of them. For this purpose, complete model of nsp1 of SARS-CoV-2 were predicted and its stability analyzed by molecular dynamics simulations in five different replicas. After main pocket validation using two control drugs and the main conformations of nsp1, molecular docking based on virtual screening were performed to identify novel potential inhibitors from DrugBank database. It has been found 16 molecules in common to all five nsp1 replica conformations. Three of them was ranked as the best compounds among them and showed better energy score than control molecules that have in vitro activity against nsp1 from SARS-CoV-2. The results pointed out here suggest new potential drugs for therapy to aid the rational drug search against COVID-19. Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "h4occy7h", "rank": 84, "score": 14.411499977111816}, {"content": "Title: Nature as a treasure trove of potential anti-SARS-CoV drug leads: a structural/mechanistic rationale Content: The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health The COVID-19 pandemic has entered a dangerous new phase In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M-pro) Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites Only three of the top candidates, viz acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future", "qid": 5, "docid": "x1s80rtb", "rank": 85, "score": 14.407600402832031}, {"content": "Title: Repurposing low\u2013molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2 Content: The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low\u2013molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low\u2013molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.", "qid": 5, "docid": "dpble2jd", "rank": 86, "score": 14.401700019836426}, {"content": "Title: Search for SARS-CoV-2 inhibitors in currently approved drugs to tackle COVID-19 pandemia Content: Different treatments are currently used for clinical management of SARS-CoV-2 infection, but little is known about their efficacy yet. Here we present ongoing results to compare currently available drugs for a variety of diseases to find out if they counteract SARS-CoV-2-induced cytopathic effect in vitro. Our goal is to prioritize antiviral activity to provide a solid evidence-driven rationale for forthcoming clinical trials. Since the most effective antiviral approaches are usually based on combined therapies that tackle the viral life cycle at different stages, we are also testing combinations of drugs that may be critical to reduce the emergence of resistant viruses. We will provide results as soon as they become available, so data should be interpreted with caution, clearly understanding the limitations of the in vitro model, that may not always reflect what could happen in vivo. Thus, our goal is to test the most active antivirals identified in adequate animal models infected with SARS-CoV-2, to add more information about possible in vivo efficacy. In turn, successful antivirals could be tested in clinical trials as treatments for infected patients, but also as pre-exposure prophylaxis to avoid novel infections until an effective and safe vaccine is developed.", "qid": 5, "docid": "ywaefpe8", "rank": 87, "score": 14.36460018157959}, {"content": "Title: Computational insights into tetracyclines as inhibitors against SARS-CoV-2 M(pro) via combinatorial molecular simulation calculations Content: The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (M(pro)). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 M(pro) crystal structure. Molecular docking simulation predicted the docking score >\u22127 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 M(pro). The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 M(pro) which can used in combinational therapy against SARS-CoV-2 infection.", "qid": 5, "docid": "8g9yyryl", "rank": 88, "score": 14.36359977722168}, {"content": "Title: Computational insights into tetracyclines as inhibitors against SARS-CoV-2 Mpro via combinatorial molecular simulation calculations Content: The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (Mpro). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 Mpro crystal structure. Molecular docking simulation predicted the docking score >-7\u00e2\u0080\u00afkcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 Mpro. The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100\u00e2\u0080\u00afns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 Mpro which can used in combinational therapy against SARS-CoV-2 infection.", "qid": 5, "docid": "xpwmoeij", "rank": 89, "score": 14.363598823547363}, {"content": "Title: Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome? Content: Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.", "qid": 5, "docid": "30g3nrj6", "rank": 90, "score": 14.348999977111816}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "hg9i6v26", "rank": 91, "score": 14.348799705505371}, {"content": "Title: Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of \u00e2\u0088\u00bc7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules like \u00ce\u00b4-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 MPro. Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "hwmg4l41", "rank": 92, "score": 14.334699630737305}, {"content": "Title: In silico Molecular Docking Analysis Targeting SARS-CoV-2 Spike Protein and Selected Herbal Constituents Content: In modern drug discovery, molecular docking analysis is routinely used to understand and predict the interaction between a drug molecule and a target protein from a microbe Drugs identified in this way may inhibit the entry and replication of pathogens in host cells The SARS-CoV-2 associated coronavirus disease, COVID-19, has become the most contagious and deadly pandemic disease in the world today In abeyance of any specific vaccine or therapeutic against SARS-CoV-2, the burgeoning situation urges a need for effective drugs to treat the virus-infected patients Herbal medicines have been used as natural remedies for treating various infectious diseases since ancient times The spike (S) protein of SARS-CoV-2 is important for the attachment and pathogenesis of the virus Therefore, this study focused on the search of useful ligands for S protein among active constituents present in common herbs that could serve as efficient remedies for COVID-19 We analysed the binding efficiency of twelve compounds present in common herbs with the S protein of SARS-CoV-2 through molecular docking analysis and also results are validated with two different docking tools The binding efficiency of ligands was scored based on their predicted pharmacological interactions coupled with binding energy estimates In docking analysis, compound \"I\" (Epigallocatechin gallate (EGCG)) was found to have the highest binding affinity with the viral S protein, followed by compounds, \"F\" (Curcumin),\"D\" (Apigenin) and \"E\" (Chrysophanol) The present study corroborates that compound \"I\" (EGCG) mostly present in the integrants of green tea, shows the highest potentiality for acting as an inhibitor of SARS-CoV-2 Further, characterization of the amino acid residues comprising the viral binding site and the nature of the hydrogen bonding involved in the ligand-receptor interaction revealed significant findings with herbal compound \"I\" (EGCG) binding to the S protein at eight amino acid residues The binding sites are situated near to the amino acids which are required for virus pathogenicity The findings of the present study need in vivo experiments to prove the utility of \"I\", \"F\",\"D\" and \"E\" compounds and their further use in making herb-based anti-SARS-CoV-2 product in near future This analysis may help to create a new ethno-drug formulation for preventing or curing the COVID-19", "qid": 5, "docid": "1sxhza50", "rank": 93, "score": 14.330300331115723}, {"content": "Title: Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches Content: WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The ever-growing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysis was performed to characterize the binding affinity of the selected drugs-the ligand, with the SARS-CoV-2 structural proteins, while high-level Simulation studies analyzed the stability of drug-protein interactions. The present study identified rutin, a bioflavonoid and the antibiotic, doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope protein. Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane protein while the anti-viral agent's simeprevir and grazoprevir showed a high binding affinity for nucleocapsid protein. All these compounds not only showed excellent pharmacokinetic properties, absorption, metabolism, minimal toxicity and bioavailability but were also remain stabilized at the active site of proteins during the MD simulation. Thus, the identified lead compounds may act as potential molecules for the development of effective drugs against SARS-CoV-2 by inhibiting the envelope formation, virion assembly and viral pathogenesis.", "qid": 5, "docid": "j92mfwkj", "rank": 94, "score": 14.314800262451172}, {"content": "Title: High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment Content: The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti-SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.", "qid": 5, "docid": "76lvmoug", "rank": 95, "score": 14.281800270080566}, {"content": "Title: High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment Content: The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti\u2013SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.", "qid": 5, "docid": "mb4tkde8", "rank": 96, "score": 14.28179931640625}, {"content": "Title: Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors Content: The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.", "qid": 5, "docid": "jnw0pnfu", "rank": 97, "score": 14.279399871826172}, {"content": "Title: Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective. Content: Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)-\uf062 production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved by clinical trials based on RAS blo", "qid": 5, "docid": "vslevssr", "rank": 98, "score": 14.262800216674805}, {"content": "Title: Repurposing old drugs as antiviral agents for coronaviruses Content: BACKGROUND: New therapeutic options to address the ongoing coronavirus disease 2019 (COVID-19) pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC50) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC50 values ranging from 11 nM to 75 \u00b5M. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, and vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.", "qid": 5, "docid": "w8ta2qgh", "rank": 99, "score": 14.258000373840332}, {"content": "Title: Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19 Content: The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (M(pro)), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for M(pro), we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against M(pro). In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed for subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the M(pro) catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.", "qid": 5, "docid": "wg1rshzk", "rank": 100, "score": 14.249600410461426}]}
{"query": "what types of rapid testing for Covid-19 have been developed?", "hits": [{"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 6, "docid": "gnaubzah", "rank": 1, "score": 9.728799819946289}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 6, "docid": "hlhhvmtu", "rank": 2, "score": 9.728798866271973}, {"content": "Title: Testing for SARS\u2010CoV\u20102: the day the world turned its attention to the clinical laboratory Content: In the last few months, an unprecedented number of laboratory tests for COVID\u201019 have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID\u201019 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the U.S. and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID\u201019. We will first address the detection of Sars\u2010Cov\u20102 directly by either nucleic acid amplification tests (NAAT) or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "qid": 6, "docid": "x7v4y1ru", "rank": 3, "score": 9.64900016784668}, {"content": "Title: Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory Content: In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "qid": 6, "docid": "r7glmi7p", "rank": 4, "score": 9.571599960327148}, {"content": "Title: SARS-CoV-2 in urine. - Should Endourologists be concerned and what PPE measures should be taken to protect the Endourologist when in theatre ? Content: SARS-CoV-2 is usually transmitted through air however several recent reports have found the virus in urine. Only 187 urine samples have been reported to have been tested in the literature to date despite over 4 million cases of respiratory Covid 19 positive cases being reported worldwide. Of these 187 urine tests 6 were positive for the virus and this persisted in urine in once case for up to 42 days. The urine sample was still positive for Covid 19 despite respiratory swabs being negative. There is a potential concern therefore that Endourologists who generally perform a high number of urine prone procedures could be at risk of exposure to the virus peri operatively. There is still confusion as to the type of PPE Endourologists should use and in what circumstances. Until it is proven that urine is not a potential source for transmission of the Virus Endourologists should have a clear knowledge of the different types of PPE available and what they should use when performing procedures.", "qid": 6, "docid": "mk3ley2o", "rank": 5, "score": 9.466400146484375}, {"content": "Title: The Role of Antibody Testing for SARS-CoV-2: Is There One? Content: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of both molecular and serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 molecular tests, submission for EUA is currently a voluntary process for manufacturers of serologic assays. The absence of FDA oversight of serologic tests is concerning, given that the commercially available serologic assays are highly variable, differing in their format, the antibody class detected, the targeted antigen and the acceptable specimen types. An added complication is the lack of a clear understanding for how such assays should be utilized and what the reported results ultimately indicate, or perhaps more importantly, what they do not indicate. Here, we provide a brief summary of the performance of a number of serologic assays reported in the literature, comment on what we do and do not know regarding our immune response to SARS-CoV-2, and provide a number of scenarios for which serologic testing will play a role in during our global response to this pandemic.", "qid": 6, "docid": "ile2md92", "rank": 6, "score": 9.2923002243042}, {"content": "Title: Evaluation of performance of two SARS-CoV-2 Rapid whole-blood finger-stick IgM-IgGCombined Antibody Tests Content: Background The SARS-CoV-2 virus is responsible for the infectious respiratory disease called COVID-19 (COronaVIrus Disease). In response to the growing COVID-19 pandemic, Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood. We conducted a real-life study to evaluate the performance of two RDTs, COVID-PRESTO and COVID-DUO, compared to the gold standard, RT-PCR. Methods RT-PCR testing of SARS-Cov-2 was performed from nasopharyngeal swab specimens collected in adult patients visiting the infectious disease department at the hospital (Orleans, France). Fingertip whole blood samples taken at different time points after onset of the disease were tested with RDTs. The specificity and sensitivity of the rapid test kits compared to test of reference (RT-PCR) were calculated. Results Among 381 patients with symptoms of COVID-19 who went to the hospital for a diagnostic, 143 patients were RT-PCR negative. Results of test with RDTs were all negative for these patients, indicating a specificity of 100% for both RDTs. In the RT-PCR positive subgroup (n=238), 133 patients were tested with COVID-PRESTO and 129 patients were tested with COVID-DUO (24 patients tested with both). The further the onset of symptoms was from the date of collection, the greater the sensitivity. The sensitivity of COVID-PRESTO test ranged from 10.00% for patients having experienced their 1st symptoms from 0 to 5 days ago to 100% in patients where symptoms had occurred more than 15 days before the date of tests. For COVID-DUO test, the sensitivity ranged from 35.71% [0-5 days] to 100% (> 15 days). Conclusion COVID-PRESTO and DUO RDTs turned out to be very specific (none false positive) and to be sensitive enough after 15 days from onset of symptom. These easy to use IgG/IgM combined test kits are the first ones allowing a screening with capillary blood sample, by typing from a finger prick. These rapid tests are particularly interesting for screening in low resource settings.", "qid": 6, "docid": "85b4lwh3", "rank": 7, "score": 9.098199844360352}, {"content": "Title: A Review of Salivary Diagnostics and Its Potential Implication in Detection of Covid-19 Content: Saliva is an exocrine secretion produced from the salivary glands and has numerous functions, such as cleansing and protection of the oral cavity, antimicrobial effects and aids in digestion. Due to the speedy development in the field of salivaomics, saliva is now well accepted as a pool of biological markers that vary from changes in biochemicals, nucleic acids and proteins to the microflora. Saliva has an immense potential as a diagnostic fluid and offers an edge over other biological fluids as its collection method does not require invasive procedure, economical and is useful for monitoring systemic health. Development of sensitive and precise salivary diagnostic tools and the formulation of defined guidelines following meticulous testing will allow salivary diagnostics to be utilised as chair side tests for various oral and systemic diseases in the near future. The coronavirus disease (Covid-19) pandemic is the biggest challenge and global health crisis for the world since World War Two. Rapid and accurate diagnosis of Covid-19 is crucial in controlling the outbreak in the community and in hospitals. Nasopharyngeal and oropharyngeal swabs are the recommended specimen types for Covid-19 diagnostic testing. The collection of these specimen types requires close contact between healthcare workers and patients and poses a risk of transmission of the virus, causes discomfort and may cause bleeding, especially in patients with condition such as thrombocytopenia. Hence, nasopharyngeal or oropharyngeal swabs are not desirable for sequential monitoring of viral load. Saliva specimens can be obtained easily as the patient is asked to spit into a sterile bottle. The collection of saliva is non-invasive and greatly minimizes the exposure of healthcare workers to Covid-19. Saliva has a high consistency rate of greater than 90% with nasopharyngeal specimens in the detection of respiratory viruses, including coronaviruses. Saliva has also been used in screening respiratory viruses among hospitalized patients without pyrexia or respiratory symptoms. SARS-CoV can be detected in saliva at high titers. Salivary diagnostics is a dynamic field that is being incorporated as part of disease diagnosis, clinical monitoring of systemic health and to make significant clinical decisions for patient care. More research is required to analyze the potential diagnostic of Covid-19 in saliva to develop rapid chair side tests for the detection of Covid-19 and it is also pivotal to improve and develop successful strategies for prevention, especially for dentists and healthcare professionals who are involved in performing aerosol-generating procedures.", "qid": 6, "docid": "awy3aans", "rank": 8, "score": 8.610600471496582}, {"content": "Title: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Content: In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19-infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.", "qid": 6, "docid": "ifu4fvwh", "rank": 9, "score": 8.605600357055664}, {"content": "Title: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Content: Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19\u2013infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.", "qid": 6, "docid": "rvg5elrc", "rank": 10, "score": 8.605599403381348}, {"content": "Title: Development and clinical application of a rapid IgM\u2010IgG combined antibody test for SARS\u2010CoV\u20102 infection diagnosis Content: The outbreak of the novel coronavirus disease (COVID\u201019) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS\u2010Cov\u20102]) nucleic acid real\u2010time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS\u2010CoV\u20102 infection, these real\u2010time PCR test kits have many limitations. In addition, high false\u2010negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point\u2010of\u2010care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS\u2010CoV\u20102 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID\u201019 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM\u2010IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS\u2010CoV\u20102 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.", "qid": 6, "docid": "a9clzlzb", "rank": 11, "score": 8.496600151062012}, {"content": "Title: Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Content: The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS-Cov-2]) nucleic acid real-time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false-negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.", "qid": 6, "docid": "g7ogkdlc", "rank": 12, "score": 8.496599197387695}, {"content": "Title: WHAT CLINICIANS NEED TO KNOW ABOUT ANTIVIRAL DRUGS AND VIRAL RESISTANCE Content: During the last decade, significant advances have been made in the development and use of antiviral agents for the successful treatment of a number of viral infections.8, 51, 57 An expanding array of antiviral drugs are currently available for the management of infections caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV), influenza A virus, respiratory syncytial virus (RSV), human immunodeficiency virus type 1 (HIV-1), papillomaviruses, and hepatitis B and C viruses. The increased number and use of antiviral agents, however, has led to the emergence of drug-resistant viruses, particularly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or hematologic malignancy or those who have undergone organ transplantation. For comprehensive reviews on specific viruses, see references 26, 41, 64, 81\u201383, and 102. Clinical situations that favor the development of resistance include long-term suppressive therapy, recurrent intermittent therapy, and the use of less than optimum doses of an antiviral agent. Generally, the emergence and isolation of drug-resistant viruses is associated more so with the therapeutic use of antiviral agents and does not seem to be caused by prophylactic treatment. As more patients fail to respond to appropriate therapy and additional antiviral agents are produced, it will also become important for diagnostic virology laboratories to provide rapid and practical antiviral susceptibility testing to assist physicians in defining drug resistance and choosing appropriate alternative therapies. This review describes the major antiviral agents, their mechanisms of action, and the development of drug resistance following antiviral therapy. A brief overview of the available phenotypic and genotypic susceptibility assays for detecting antiviral resistance is also discussed.", "qid": 6, "docid": "6324190r", "rank": 13, "score": 8.462699890136719}, {"content": "Title: Current and emerging diagnostic tests available for the novel COVID-19 global pandemic Content: On March 11, 2020 the World Health Organization (WHO) upgraded the status of the coronavirus disease 2019 (COVID-19) outbreak from epidemic to a global pandemic. This infection is caused by a novel coronavirus, SARS-CoV-2. Several rapid diagnostic tests have been developed at an astonishing pace; however, COVID-19 requires more highly specific rapid point-of-care diagnostic tests. This review describes the currently available testing approaches, as well as the available test assays including the Xpert\u00ae Xpress SARS-CoV-2 test (takes (~)45 min) and Abbott ID COVID-19 test (5 min) as easy to use point-of-care tests for diagnosis of novel COVID-19 that have so far received the US Food and Drug Administration emergency use authorizations clearance. This review is correct as of the date published and will be updated as more diagnostic tests come to light.", "qid": 6, "docid": "1dr4r3n4", "rank": 14, "score": 8.441300392150879}, {"content": "Title: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response Content: The most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is known about the initial responses of human lung alveoli to SARS-CoV-2 infection due in part to inability to access these cells from patients, particularly at early stages of disease. Here we present an in vitro human model that simulates the initial apical infection of the distal lung epithelium with SARS-CoV-2, using AT2s that have been adapted to air-liquid interface culture after their derivation from induced pluripotent stem cells (iAT2s). We find that SARS-CoV-2 induces a rapid global transcriptomic change in infected iAT2s characterized by a shift to an inflammatory phenotype predominated by the secretion of cytokines encoded by NF-kB target genes, delayed epithelial interferon responses, and rapid loss of the mature lung alveolar epithelial program. Over time, infected iAT2s exhibit cellular toxicity that can result in the death of these key alveolar facultative progenitors, as is observed in vivo in COVID-19 lung autopsies. Importantly, drug testing using iAT2s confirmed the efficacy of TMPRSS2 protease inhibition, validating putative mechanisms used for viral entry in human alveolar cells. Our model system reveals the cell-intrinsic responses of a key lung target cell to infection, providing a platform for further drug development and facilitating a deeper understanding of COVID-19 pathogenesis.", "qid": 6, "docid": "ulb3vy01", "rank": 15, "score": 8.436800003051758}, {"content": "Title: Consensus Summary Report for CEPI/BC March 12-13, 2020 Meeting: Assessment of Risk of Disease Enhancement with COVID-19 Vaccines Content: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of \u201cdisease enhancement\u201d has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory Syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.", "qid": 6, "docid": "eeh2a0t8", "rank": 16, "score": 8.431699752807617}, {"content": "Title: Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines Content: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of \"disease enhancement\" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.", "qid": 6, "docid": "g4ak4t31", "rank": 17, "score": 8.4316987991333}, {"content": "Title: Clinical Testing For Covid-19 Content: Abstract As the novel coronavirus SARS-CoV-2 caused COVID-19 cases in the United States the initial test was developed and performed at the Center for Disease Control (CDC). As the number of cases increased the demand for tests multiplied, leading the CDC to utilize the Emergency Utilization Authorization to allow clinical and commercial laboratories to develop tests to detect the presence of the virus. Many nucleic acid tests based on reverse transcriptase-polymerase chain reaction (RT-PCR) were developed, each with different techniques, specifications and turnaround time. As the illnesses turned into a pandemic, testing became more crucial. The test supply became inadequate to meet the need that it had to be prioritized according to guidance. For surveillance, the need for serologic tests emerged. Here we review the timeline of test development, the turn-around times, the various approved tests and compare them as regards the genes they detect. We concentrate on the point-of-care tests and discuss the basis for new serologic tests. We discuss the testing guidance for prioritization and their application in a hospital setting. As SARS-CoV-2 virus arrived in the USA causing the COVID-19 illness, one of the most talked about issues in the management of the disease and the resulting pandemic has been clinical testing. A unique situation arose of a communicable and highly contagious disease necessitating the rapid diagnosis of patients and the identification of non-symptomatic infected persons. Unfortunately, the USA did not have a Food and Drug Administration (FDA) approved laboratory test for the illness. The FDA ultimately utilized its Emergency Use Authorizations (EUA) on February 4, 2020 to allow for more rapid and widespread development and implementation of in-vitro testing.1 Indeed, companies and organizations utilized the EUA to file applications for new tests based on different methodologies, amounting to 48 applications in the span of 3 months from the beginning of February to the end of April 2020. In addition, multiple other tests were put in place under a separate authorization by a Presidential memorandum in early March allowing laboratories that carry Clinical Laboratory Improvement Amendment (CLIA) certification to put tests in place without an EUA from the FDA. This created an unprecedented situation where the medical community and the public may not be familiar with the various new tests for COVID-19 that are offered to patients and hospitals. The purpose of this review is to provide information, up-to-date as of the date of submission of the manuscript to the journal, on the various tests that have been developed, their scientific basis and their interpretation. We give a real-world example demonstrating the time lag in the return of test results and review testing prioritization guidance since the supply of tests remains below the perceived need.", "qid": 6, "docid": "isswwnzn", "rank": 18, "score": 8.412300109863281}, {"content": "Title: Care of ophthalmological patients during the COVID-19 pandemic: A rapid scoping review. Content: Introduction A new type of coronavirus (SARS-CoV-2) causes a respiratory distress syndrome that has been called COVID-19 and has generated an unprecedented pandemic. Serious complications include pneumonia, and mortality ranges from 2 to 5%. Until March 26, the World Health Organization reports 462 684 confirmed cases and 20 834 deaths worldwide. Dissemination occurs from aerosols or respiratory droplets. Different scientific societies have published clinical practice guidelines regarding ophthalmic care in the COVID-19 pandemic, but the information is presented inconsistently, which makes decision-making difficult. Methods We conducted a sensitive bibliographic search in EMBASE and ophthalmic society webpages, of the clinical practice guidelines of ophthalmic care in pandemic COVID-19. We extracted the recommendations, organizing them into three categories: \"Which patients to attend\", \"How should the clinic work\", and \"What interventions should be avoided\". For each guideline, we assessed whether the search was systematic and whether the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was followed. Results Fourteen relevant articles were found. Fifty-one recommendations were extracted and are shown in a summary table. None are based on a systematic search for evidence, nor do any use GRADE to develop the recommendations. Conclusions The clinical practice guidelines that we reviewed all recommend rescheduling all non-urgent consultations and surgeries, reinforcing contact precautions, the use of personal protection elements, and the disinfection of surfaces and instruments. The guidelines should be improved by incorporating systematic searches for evidence, using GRADE for recommendations, and Appraisal of Guidelines for Research and Evaluation (AGREE II) for reporting.", "qid": 6, "docid": "8zqkel14", "rank": 19, "score": 8.3774995803833}, {"content": "Title: SARS-CoV-2 qRT-PCR Ct value distribution in Japan and possible utility of rapid antigen testing kit Content: The exact pathology of COVID-19 remains mostly unclear, and accurate epidemiological understanding and rapid testing are crucial to overcome this disease. Several types of nucleic acid tests (NAT) have been used in Japan, but information about the viral RNA load, determined by Ct values, of the patients is limited due to the small number of patients tested in each clinical institution and lack of standardization of the testing kits. We have been performing the qRT-PCR tests established by NIID, and the mean Ct value distribution of 62 cases, which are deemed (first-visit) patients, among the total of 88 positive cases tested in a 4-day window of early April, was 24.9 with SD=5.45. Recently approved antigen testing kits were also used in the same samples (62 positives) along with 100 negative cases, and it revealed the positive predictive value of 80.6% and negative predictive value of 100%, with an overall agreement rate of 92.6%. These results indicate that a certain number of patients with lower Ct values, existed in Japan when SARS-CoV-2 virus started to spread. The newly approved rapid antigen testing kit will be a useful tool to identify such populations rapidly.", "qid": 6, "docid": "fyshred0", "rank": 20, "score": 8.36299991607666}, {"content": "Title: Atenci\u00f3n de pacientes oftalmol\u00f3gicos durante la pandemia COVID-19: revisi\u00f3n panor\u00e1mica r\u00e1pida./ Atenci\u00f3n de pacientes oftalmol\u00f3gicos durante la pandemia COVID-19: revisi\u00f3n panor\u00e1mica r\u00e1pida./ Care of ophthalmological patients during the COVID-19 pandemic: A rapid scoping review Content: Introduction: A new type of coronavirus (SARS-CoV-2) causes a respiratory distress syndrome that has been called COVID-19 and has generated an unprecedented pandemic. Serious complications include pneumonia, and mortality ranges from 2 to 5%. Until March 26, the World Health Organization reports 462 684 confirmed cases and 20 834 deaths worldwide. Dissemination occurs from aerosols or respiratory droplets. Different scientific societies have published clinical practice guidelines regarding ophthalmic care in the COVID-19 pandemic, but the information is presented inconsistently, which makes decision-making difficult. Methods: We conducted a sensitive bibliographic search in EMBASE and ophthalmic society webpages, of the clinical practice guidelines of ophthalmic care in pandemic COVID-19. We extracted the recommendations, organizing them into three categories: \"Which patients to attend\", \"How should the clinic work\", and \"What interventions should be avoided\". For each guideline, we assessed whether the search was systematic and whether the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was followed. Results: Fourteen relevant articles were found. Fifty-one recommendations were extracted and are shown in a summary table. None are based on a systematic search for evidence, nor do any use GRADE to develop the recommendations. Conclusions: The clinical practice guidelines that we reviewed all recommend rescheduling all non-urgent consultations and surgeries, reinforcing contact precautions, the use of personal protection elements, and the disinfection of surfaces and instruments. The guidelines should be improved by incorporating systematic searches for evidence, using GRADE for recommendations, and Appraisal of Guidelines for Research and Evaluation (AGREE II) for reporting.", "qid": 6, "docid": "of7nk5ox", "rank": 21, "score": 8.358699798583984}, {"content": "Title: Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection. Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the United States Center for Disease Control & Prevention, takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own labs. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 6, "docid": "b3wp314u", "rank": 22, "score": 8.351200103759766}, {"content": "Title: Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid-based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the U.S. Centers for Disease Control and Prevention takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply, and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own laboratories. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 6, "docid": "opdva99w", "rank": 23, "score": 8.35119915008545}, {"content": "Title: COVID-19 vaccines: Knowing the unknown Content: Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain - some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.", "qid": 6, "docid": "hotn7qha", "rank": 24, "score": 8.33590030670166}, {"content": "Title: COVID\u201019 vaccines: knowing the unknown Content: Vaccine development against SARS\u2010CoV\u20102 has drawn attention around the globe due to the exploding pandemic. Although COVID\u201019 is caused by a new coronavirus, SARS\u2010CoV\u20102, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID\u201019 vaccine. However, important knowledge gaps remain \u2013 some are specific to SARS\u2010CoV\u20102, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID\u201019 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID\u201019 has been remarkable. We are therefore optimistic about the rapid development of COVID\u201019 vaccine. This article is protected by copyright. All rights reserved", "qid": 6, "docid": "tdvb0fhv", "rank": 25, "score": 8.335899353027344}, {"content": "Title: Healthcare workers experiences of working on the frontline and views about support during COVID-19 and comparable pandemics: A rapid review and meta-synthesis Content: Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline healthcare workers and growing calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers own perspectives or what their views are about support. This rapid review identified 40 qualitative studies which have explored healthcare workers experiences and views from previous pandemics, including and comparable to COVID-19. Meta-synthesis of this qualitative data using thematic analysis derived eight key themes which transcended pandemics, time, and geographical boundaries. This pandemic is not unprecedented; the themes that arose from previous pandemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of these previous pandemics, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.", "qid": 6, "docid": "6gc7smqf", "rank": 26, "score": 8.30739974975586}, {"content": "Title: An insight into the epitope-based peptide vaccine design strategy and studies against COVID-19 Content: SARS-CoV-2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID-19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope-based peptide vaccines outshine with their low-cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID-19 have been summarized and detailed information about the epitope-based peptide vaccines against COVID-19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on-going peptide vaccine studies against SARS-CoV-2.", "qid": 6, "docid": "j6gn8exx", "rank": 27, "score": 8.281399726867676}, {"content": "Title: Does coronavirus affect the audio-vestibular system? A rapid systematic review Content: Objective: This rapid systematic review investigated audio-vestibular symptoms associated with coronavirus.Design: The protocol for the rapid review was registered in the International Prospective Register of Systematic Reviews and the review methods were developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the National Institute of Heath quality assessment tools.Study sample: After rejecting more than 2300 records, there were five case reports and two cross-sectional studies that met the inclusion criteria.Results: No records of audio-vestibular symptoms were reported with the earlier types of coronavirus (i.e. severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]). Reports of hearing loss, tinnitus, and vertigo have rarely been reported in individuals who tested positive for the SARS-CoV-2.Conclusion: Reports of audio-vestibular symptoms in confirmed COVID-19 cases are few, with mostly minor symptoms, and the studies are of poor quality. Emphasis over time is likely to shift from life-threatening concerns to longer-term health-related consequences such as audio-vestibular dysfunction. High-quality studies are needed to investigate the acute effects of COVID-19, as well as for understanding long-term risks, on the audio-vestibular system. Review registration: Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020184932).", "qid": 6, "docid": "luitq92d", "rank": 28, "score": 8.277899742126465}, {"content": "Title: Does coronavirus affect the audio-vestibular system? A rapid systematic review. Content: Objective: This rapid systematic review investigated audio-vestibular symptoms associated with coronavirus.Design: The protocol for the rapid review was registered in the International Prospective Register of Systematic Reviews and the review methods were developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the National Institute of Heath quality assessment tools.Study sample: After rejecting more than 2300 records, there were five case reports and two cross-sectional studies that met the inclusion criteria.Results: No records of audio-vestibular symptoms were reported with the earlier types of coronavirus (i.e. severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]). Reports of hearing loss, tinnitus, and vertigo have rarely been reported in individuals who tested positive for the SARS-CoV-2.Conclusion: Reports of audio-vestibular symptoms in confirmed COVID-19 cases are few, with mostly minor symptoms, and the studies are of poor quality. Emphasis over time is likely to shift from life-threatening concerns to longer-term health-related consequences such as audio-vestibular dysfunction. High-quality studies are needed to investigate the acute effects of COVID-19, as well as for understanding long-term risks, on the audio-vestibular system. Review registration: Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020184932).", "qid": 6, "docid": "uivoe66n", "rank": 29, "score": 8.277898788452148}, {"content": "Title: Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling Content: Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.(1\u20133) Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.(4) Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,(5) these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19.", "qid": 6, "docid": "rycluj9p", "rank": 30, "score": 8.23390007019043}, {"content": "Title: Inference for a test-negative case-control study with added controls Content: Test-negative designs with added controls have recently been proposed to study COVID-19. An individual is test-positive or test-negative accordingly if they took a test for a disease but tested positive or tested negative. Adding a control group to a comparison of test-positives vs test-negatives is useful since additional comparison of test-positives vs controls can have potential biases different from the first comparison. Bonferroni correction ensures necessary type-I error control for these two comparisons done simultaneously. We propose two new methods for inference which have better interpretability and higher statistical power for these designs. These methods add a third comparison that is essentially independent of the first comparison, but our proposed second method often pays much less for these three comparisons than what a Bonferroni correction would pay for the two comparisons.", "qid": 6, "docid": "0tkg57em", "rank": 31, "score": 8.200400352478027}, {"content": "Title: Rapid development of COVID-19 rapid diagnostics for low resource settings: accelerating delivery through transparency, responsiveness, and open collaboration Content: In January, Mologic, embarked on a product development pathway for COVID-19 diagnostics focusing on ELISA and rapid diagnostic tests (RDTs), with anticipated funding from Wellcome Trust and DFID. 755 clinical samples from known COVID-19 patients and hospital negative controls were tested on Mologics IgG ELISA. The reported sensitivity on 191 SGUL prospectively enrolled patients was 95% on day 7 or more post diagnosis, and 97% 10 days or more post-diagnosis. A specificity panel comprising 564 samples pre-December 2019 were tested to include most common respiratory pathogens, other types of coronavirus, and flaviviruses. Specificity in this panel was 97%. This is the first in a series of Mologic products for COVID-19, which will be deployed for COVID-19 diagnosis, contact tracing and sero-epidemiological studies to estimate disease burden and transmission with a focus on ensuring access, affordability, and availability to lowest resource settings.", "qid": 6, "docid": "nol2n8fo", "rank": 32, "score": 8.192899703979492}, {"content": "Title: Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2 Content: The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 102 RNA copies close to that of qRT-PCR. Notably, the assay has exhibited a rapid detection span of 30\u00e2\u0080 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.", "qid": 6, "docid": "77jpm4o0", "rank": 33, "score": 8.123499870300293}, {"content": "Title: Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2 Content: The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10(2) RNA copies close to that of qRT-PCR. Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.", "qid": 6, "docid": "sdde8bgd", "rank": 34, "score": 8.123498916625977}, {"content": "Title: Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2. Content: Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "qid": 6, "docid": "7ur8hr23", "rank": 35, "score": 8.117799758911133}, {"content": "Title: Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2 Content: Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "qid": 6, "docid": "xa1v5t63", "rank": 36, "score": 8.117798805236816}, {"content": "Title: Public Health Responses to COVID-19 Outbreaks on Cruise Ships \u2014 Worldwide, February\u2013March 2020 Content: What is already known about this topic? Cruise ships are often settings for outbreaks of infectious diseases because of their closed environment and contact between travelers from many countries What is added by this report? More than 800 cases of laboratory-confirmed COVID-19 cases occurred during outbreaks on three cruise ship voyages, and cases linked to several additional cruises have been reported across the United States Transmission occurred across multiple voyages from ship to ship by crew members;both crew members and passengers were affected;10 deaths associated with cruise ships have been reported to date What are the implications for public health practice? Outbreaks of COVID-19 on cruise ships pose a risk for rapid spread of disease beyond the voyage Aggressive efforts are required to contain spread All persons should defer all cruise travel worldwide during the COVID-19 pandemic", "qid": 6, "docid": "9b6j5lk0", "rank": 37, "score": 8.114700317382812}, {"content": "Title: The development of a multiplex real-time PCR for the detection of herpes simplex virus 1 and 2, varizella zoster virus, adenovirus and Chlamydia trachomatis from eye swabs Content: Abstract Infectious conjunctivitis can be difficult to distinguish clinically due to the considerable overlap in clinical presentation so clinical diagnosis of conjunctivitis is often insufficient. It is therefore necessary to have a rapid diagnostic test that differentiates between the different causes of infectious conjunctivitis. Screening clinical samples by sample type/syndrome based multiplex real time PCR would allow for rapid detection of a variety of pathogens simultaneously, which will in turn aid in the treatment and clinical management of the patient. A multiplex real-time PCR assay for rapid and simultaneous detection of HSV 1 and 2, VZV, adenovirus and Chlamydia trachomatis (C. trachomatis) from eye swabs was developed and evaluated. The multiplex assay was shown to be sensitive, specific and robust. Reductions in sample turn around times have been achieved by reducing the amount of separate tests needed to be carried out.", "qid": 6, "docid": "ujo72w06", "rank": 38, "score": 8.028599739074707}, {"content": "Title: Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019 Content: Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID\u201019). This study was conducted to evaluate the diagnostic performance of an immunochromatography\u2010based assay of human serum for COVID\u201019. The present study enrolled 149 subjects who had been tested by real\u2010time reverse transcription\u2010polymerase chain reaction (RT\u2010PCR) for COVID\u201019 and were classified into two groups: 70 who were positive for COVID\u201019 and 79 who were negative for COVID\u201019 based on RT\u2010PCR. An immunochromatography\u2010based COVID\u201019 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT\u2010PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID\u201019 and in three subjects (3.8%) classified as negative for COVID\u201019. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1\u201097.6) and 96.2% (95% CI: 89.3\u201099.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903\u20100.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography\u2010based COVID\u201019 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID\u201019, especially in the presence of IgM or IgG antibodies.", "qid": 6, "docid": "5dov14wy", "rank": 39, "score": 8.01550006866455}, {"content": "Title: Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019 Content: Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID-19). This study was conducted to evaluate the diagnostic performance of an immunochromatography-based assay of human serum for COVID-19. The present study enrolled 149 subjects who had been tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 and were classified into two groups: 70 who were positive for COVID-19 and 79 who were negative for COVID-19 based on RT-PCR. An immunochromatography-based COVID-19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT-PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID-19 and in three subjects (3.8%) classified as negative for COVID-19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1-97.6) and 96.2% (95% CI: 89.3-99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903-0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography-based COVID-19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID-19, especially in the presence of IgM or IgG antibodies.", "qid": 6, "docid": "yo5dqwkk", "rank": 40, "score": 8.015499114990234}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "qid": 6, "docid": "3mnmib3o", "rank": 41, "score": 8.011500358581543}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research. Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "qid": 6, "docid": "sn72mkzq", "rank": 42, "score": 8.011499404907227}, {"content": "Title: Implementation science in times of Covid-19 Content: The emergence of SARS-CoV-2/Covid-19 affects all of us and is associated with rapid and massive changes in healthcare and societies. As a response, a range of interventions for patients and populations have been implemented in health and preventive settings, or need to be implemented in the short and long term. Implementation science offers a multidisciplinary perspective and systematic approach for the design, evaluation and analysis of programmes and policies to enhance implementation. The emergence of Covid-19 provides an urgent need to develop new perspectives and approaches in implementation science, such as the addition of innovative and rigorous approaches to the collection, use and analysis of \u2018real-world\u2019 data. Above all, we hope that implementation scientists will focus on what they can contribute to manage Covid-19 and its consequences for people, healthcare and society.", "qid": 6, "docid": "1p1917my", "rank": 43, "score": 8.010199546813965}, {"content": "Title: Implementation science in times of Covid-19 Content: The emergence of SARS-CoV-2/Covid-19 affects all of us and is associated with rapid and massive changes in healthcare and societies. As a response, a range of interventions for patients and populations have been implemented in health and preventive settings, or need to be implemented in the short and long term. Implementation science offers a multidisciplinary perspective and systematic approach for the design, evaluation and analysis of programmes and policies to enhance implementation. The emergence of Covid-19 provides an urgent need to develop new perspectives and approaches in implementation science, such as the addition of innovative and rigorous approaches to the collection, use and analysis of 'real-world' data. Above all, we hope that implementation scientists will focus on what they can contribute to manage Covid-19 and its consequences for people, healthcare and society.", "qid": 6, "docid": "212qr1rw", "rank": 44, "score": 8.010198593139648}, {"content": "Title: COVID-19 in a Patient Presenting with Syncope and a Normal Chest X-ray Content: SARS-CoV-2 is a novel virus that has now affected hundreds of thousands of individuals across the world. Amidst this global pandemic, maintaining a high index of suspicion, rapid testing capacity, and infection control measures are required to curtail the virus' rapid spread. While fever and respiratory symptoms have been commonly used to identify COVID-19 suspects, we present an elderly female who arrived to the hospital after a syncopal episode. She was afebrile with a normal chest X-ray and there was no suspicion of COVID-19. She then developed a fever and tested positive for COVID-19. Our unique case underscores the increasing diversity of COVID-19 presentations and potential for initial mis- diagnosis and delay in implementing proper precautions.", "qid": 6, "docid": "c5dm1d6t", "rank": 45, "score": 8.0024995803833}, {"content": "Title: COVID-19 in a Patient Presenting with Syncope and a Normal Chest X-ray. Content: SARS-CoV-2 is a novel virus that has now affected hundreds of thousands of individuals across the world. Amidst this global pandemic, maintaining a high index of suspicion, rapid testing capacity, and infection control measures are required to curtail the virus' rapid spread. While fever and respiratory symptoms have been commonly used to identify COVID-19 suspects, we present an elderly female who arrived to the hospital after a syncopal episode. She was afebrile with a normal chest X-ray and there was no suspicion of COVID-19. She then developed a fever and tested positive for COVID-19. Our unique case underscores the increasing diversity of COVID-19 presentations and potential for initial mis- diagnosis and delay in implementing proper precautions.", "qid": 6, "docid": "v5uz8rsu", "rank": 46, "score": 8.002498626708984}, {"content": "Title: CoVID-19 in Japan: What could happen in the future? Content: COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately.", "qid": 6, "docid": "u6b8iwr0", "rank": 47, "score": 8.001700401306152}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov SUPPLEMENTARY INFORMATION:", "qid": 6, "docid": "st5idleq", "rank": 48, "score": 8.001099586486816}, {"content": "Title: Clinical Characteristics and Risk factors for developed COVID-19 patients transferring to designated hospital from Jianghan Fangcang shelter Hospital: a retrospective, observational study Content: Background The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. Fangcang shelter hospitals have been applied in COVID-19 to ease ongoing shortage of medical resources in Wuhan since February 2020. Methods This study enrolled all cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan in Wuhan from Feb 5th to Mar 9th, 2020. Diagnosis of COVID-19 was based on the National health commission of China. Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Laboratory tests included biochemical indicators and nucleic acid tests by throat swabs have been performed as well. Findings A total of 1327 patients reached the criteria of isolation release. Meanwhile, 521 patients have been transferred to the designated hospitals for further treatment, including severe type, fever more than 3 days, and severe comorbidity. The case-severity rate (rate of mild or moderate type transforming to severe type) was 3.0% in the shelter hospital. The patients from mild or moderate type to severe type showed the following clinical characteristics: the median incubation (onset to shelter) period was 10 days; they were all symptomatic at admission; fever, cough, and fatigue were the most common symptoms; hypertension, diabetes and coronary heart diseases were common co-morbidities; most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg per L; bilateral distribution and ground-glass opacity were the most common manifestations in chest CT. Interpretation The potential risk factors of fever, fatigue, high level of C-reactive protein were the risk factors to identify the progression of COVID-19 patients with mild or moderate type. Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms transfer to a designated hospital. Early application of the Fangcang shelter hospital may contribute to decrease the ratio of mild transforming to severe patients. Funding No specific grant from any funding was applied to this research.", "qid": 6, "docid": "67r1qmc9", "rank": 49, "score": 7.948599815368652}, {"content": "Title: Products in a Pandemic: Liability for Medical Products and the Fight against COVID-19 Content: A multitude of medical products are being developed and produced as part of efforts to tackle COVID-19. They are varied in nature and range from test kits to tracing apps, protective equipment, ventilators, medicines and, of course, vaccines. The design, testing and manufacture of many of these products differs from production in normal times due to the urgency of the situation and the rapid increase in demand created by the pandemic. This article considers the legal issues arising as a result of the production of emergency products, particularly from a products liability perspective. To what extent do existing concepts under the European Product Liability Directive, such as defect, causation and the various defences, permit the pandemic to be taken into account when a Court is considering issues of liability? What is the impact on liability of the modified regulatory regime? In light of that discussion, the case for alternative responses is examined from a comparative and European perspective, including the issue of Government indemnities for the manufacturers of products, legal exemptions from liability and alternative no-fault compensation schemes.", "qid": 6, "docid": "sjub0mwv", "rank": 50, "score": 7.947000026702881}, {"content": "Title: Post-mortem surveillance of bovine tuberculosis in Ireland: herd-level variation in the probability of herds disclosed with lesions at routine slaughter to have skin test reactors at follow-up test Content: Post-mortem surveillance in Ireland discloses skin-test negative cattle with presumptive evidence of infection of Mycobacterium bovis (lesions at routine slaughter (LRS)), the causative agent of bovine tuberculosis (bTB). Laboratory confirmation of lesions has impacts on trade restrictions for herds, therefore if laboratory capacity was diminished, how herds are treated would require an informed risk policy. Here we report the proportion of herds with subsequent evidence of within-herd transmission, based on skin-test results. We assess how herd-size, herd-type, and bTB-history affect the probability of additional reactors at follow-up test using univariable and multivariable random-effects models. The study represents a rapid response to developing an evidential base for policy demands during an extraordinary event, the COVID-19 epidemic in Ireland. A dataset from 2005 to 2019 of breakdowns were collated. Overall, 20,116 breakdowns were initiated by LRS cases. During the index tests of these breakdowns, 3931 revealed &#8805;1 skin-test reactor animals (19.54%; &#8805;1 standard reactors: 3827; 19.02%). Increasing herd-size was associated with reactor disclosure on follow-up. For small herds (<33 animals), 11.74% of follow-up tests disclosed &#8805;1 reactor; 24.63% of follow-up tests from very large herds (>137) disclosed &#8805;1 reactors. Beef (13.87%) and \"other\" (13%) herd production types had lower proportion of index tests with reactors in comparison with dairy (28.27%) or suckler (20.48%) herds. Historic breakdown size during the previous 3-years was associated reactor disclosure risk on follow-up. Our results are useful for rapid tailored policy development aimed at identifying higher risk herds.", "qid": 6, "docid": "iq5yuwwv", "rank": 51, "score": 7.9257001876831055}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features , Copyright Notice (C) 2020 Royal College of Physicians", "qid": 6, "docid": "9griuata", "rank": 52, "score": 7.9197001457214355}, {"content": "Title: Road toward rapid-molecular point of care test to detect novel SARS-coronavirus 2019 (COVID-19): Review from updated literature Content: Coronavirus disease 2019 (COVID-19) named by the WHO as a result of the global public health emergency. COVID-19 is caused by a new coronavirus named as novel coronavirus (2019-nCOV). From the first case reported in December 2019 it is now a pandemic situation and a major public health emergency. The COVID-19 transmission rate is very high, infecting two to three persons on average with contact to an already infected person. There is a need for the health system, specially in developing countries such as in Pakistan, to combat such a novel disease by rapid, accurate, and high quality diagnostic testing in order to screen suspected cases and also surveillance of the disease. A rapid, accurate and low-cost diagnostic point-of-care device is needed for timely diagnosis of COVID-19 and is essential to combat such outbreaks for compelling preventive measures against the disease spread. This review is to highlight the importance of point-of-care diagnostics device for robust and accurate diagnosis of COVID-19 in physician offices and other urgent healthcare-type settings and encourage academics and stake holders towards advancement in order to control outbreaks and develop the public health surveillance system.", "qid": 6, "docid": "yvsv8ns2", "rank": 53, "score": 7.907800197601318}, {"content": "Title: Types of Assays for SARS-CoV-2 Testing: A Review Content: Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "qid": 6, "docid": "qexn0nuy", "rank": 54, "score": 7.899600028991699}, {"content": "Title: Types of Assays for SARS-CoV-2 Testing: A Review. Content: Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "qid": 6, "docid": "zyrzfm40", "rank": 55, "score": 7.899599075317383}, {"content": "Title: The Rapid Deployment of a 3D Printed Latticed Nasopharyngeal Swab for COVID-19 Testing Made Using Digital Light Synthesis Content: The novel coronavirus disease (COVID-19) has caused a pandemic that has disrupted supply chains globally. This black swan event is challenging industries from all sectors of the economy including those industries directly needed to produce items that safeguard us from the disease itself, especially personal protection equipment (N95 masks, face shields) and much needed consumables associated with testing and vaccine delivery (swabs, vials and viral transfer medium). Digital manufacturing, especially 3D printing, has been promulgated as an important approach for the rapid development of new products as well as a replacement manufacturing technique for many traditional manufacturing methods, including injection molding, when supply chains are disrupted. Herein we report the use of Digital Light Synthesis (DLS) for the design and large-scale deployment of nasopharyngeal (NP) swabs for testing of coronavirus SARS-CoV-2 infections in humans. NP swabs have been one of society's essential products hardest hit by the supply chain disruptions caused by COVID-19. A latticed tip NP swab was designed and fabricated by DLS from a liquid resin previously developed and approved for use to make dental night guard devices. These latticed NP swabs demonstrated non-inferiority in a human clinical study of patients suspected of being infected with SARS-CoV-2.", "qid": 6, "docid": "luifhy6g", "rank": 56, "score": 7.897299766540527}, {"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 6, "docid": "khfiy0m2", "rank": 57, "score": 7.88640022277832}, {"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds. Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 6, "docid": "y883anmp", "rank": 58, "score": 7.886399269104004}, {"content": "Title: COVID-19 and diabetes: What have we learned so far? Content: COVID-19 and diabetes are both pandemics with major impacts on global public health. While the response to COVID-19 has been rapid and progressive to reduce risk of harm, the response to the diabetes pandemic has been somewhat more muted. People with diabetes have been disproportionately affected by COVID-19, with growing evidence of higher mortality and morbidity. In this article, we discuss the impact of COVID-19 on our diabetes service in an urban area in the UK. We discuss the impact on our patients and ourselves, and the possible lessons we can carry into the future.", "qid": 6, "docid": "dbclnrwr", "rank": 59, "score": 7.852799892425537}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next-generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present the Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2000 sequences per submission and the analysis of a new whole-genome sequence will take approximately 1 min. The tool has been tested and validated with hundreds of whole genomes from 10 coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY AND IMPLEMENTATION: https://www.genomedetective.com/app/typingtool/cov. CONTACT: koen@emweb.be or deoliveira@ukzn.ac.za. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "qid": 6, "docid": "88hswyln", "rank": 60, "score": 7.843100070953369}, {"content": "Title: A Molecularly Imprinted Polymer-Based Technology for Rapid Testing of COVID-19 Content: The outbreak of COVID-19 has taken a large number of lives since 2019 and the death toll continues to increase all over the world. Recent data reports that about 27 lacs of people are infected with this virus till date and around 2 lacs are dead due to this pandemic. The situation in India is no way better. In India, almost all the states have become victim of this deadly pandemic. Considering the enormous population in India, citizens here are facing acute shortage of detection kits and many are dying even before the knowledge of their infection. The present treatise proposes a molecularly imprinted polymer (MIP) based technique for simple and rapid detection of COVID-19. The technique will be inexpensive, selective, reusable and easy to handle. It has been already implemented in our laboratory in order to detect the taste contributing agents found in tea. This article discusses the detailed methodology and the resultant analytical characteristic of the sensors developed so far and also outlines the suitability of the MIP technique towards fabrication of testing kits for rapid detection of COVID-19.", "qid": 6, "docid": "hmt9ojvc", "rank": 61, "score": 7.837600231170654}, {"content": "Title: A Veterinary Vaccine Development Process Map to assist in the development of new vaccines Content: Abstract The UK Government recognised the importance of vaccines in the control of new emerging disease threats and in 2015 established the UK Vaccine Network to focus on specific areas of need. One of these was the understanding of what is involved in the development of a new vaccine and what are the potential bottlenecks to a rapid response in the face of a pandemic such as COVID-19. A Working Group was established to initially produce a Vaccine Development Process Map for a Human Vaccine. However, in view of the importance of animal wellbeing and the significant impact of diseases with Zoonotic potential, a similar Map has been created outlining the Veterinary Vaccine Development Process. This paper describes the production of that Map and covers the process from the generation of a Target Product Profile (TPP) through Discovery and Feasibility, and on to Product Development and Registration.", "qid": 6, "docid": "wtjlqhv4", "rank": 62, "score": 7.835899829864502}, {"content": "Title: Post-mortem surveillance of bovine tuberculosis in Ireland: herd-level variation in the probability of herds disclosed with lesions at routine slaughter to have skin test reactors at follow-up test Content: Post-mortem surveillance in Ireland discloses skin-test negative cattle with presumptive evidence of infection of Mycobacterium bovis (lesions at routine slaughter (LRS)), the causative agent of bovine tuberculosis (bTB). Laboratory confirmation of lesions has impacts on trade restrictions for herds, therefore if laboratory capacity was diminished, how herds are treated would require an informed risk policy. Here we report the proportion of herds with subsequent evidence of within-herd transmission, based on skin-test results. We assess how herd-size, herd-type, and bTB-history affect the probability of additional reactors at follow-up test using univariable and multivariable random-effects models. The study represents a rapid response to developing an evidential base for policy demands during an extraordinary event, the COVID-19 epidemic in Ireland. A dataset from 2005 to 2019 of breakdowns were collated. Overall, 20,116 breakdowns were initiated by LRS cases. During the index tests of these breakdowns, 3931 revealed \u22651 skin-test reactor animals (19.54%; \u22651 standard reactors: 3827; 19.02%). Increasing herd-size was associated with reactor disclosure on follow-up. For small herds (<33 animals), 11.74% of follow-up tests disclosed \u22651 reactor; 24.63% of follow-up tests from very large herds (>137) disclosed \u22651 reactors. Beef (13.87%) and \u201cother\u201d (13%) herd production types had lower proportion of index tests with reactors in comparison with dairy (28.27%) or suckler (20.48%) herds. Historic breakdown size during the previous 3-years was associated reactor disclosure risk on follow-up. Our results are useful for rapid tailored policy development aimed at identifying higher risk herds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11259-020-09777-w) contains supplementary material, which is available to authorized users.", "qid": 6, "docid": "rxu79by8", "rank": 63, "score": 7.8180999755859375}, {"content": "Title: Magnetic Lateral Flow Immunoassays Content: A new generation of magnetic lateral flow immunoassays is emerging as powerful tool for diagnostics. They rely on the use of magnetic nanoparticles (MNP) as detecting label, replacing conventional gold or latex beads. MNPs can be sensed and quantified by means of external devices, allowing the development of immunochromatographic tests with a quantitative capability. Moreover, they have an added advantage because they can be used for immunomagnetic separation (IMS), with improvements in selectivity and sensitivity. In this paper, we have reviewed the current knowledge on magnetic-lateral flow immunoassay (LFIA), coupled with both research and commercially available instruments. The work in the literature has been classified in two categories: optical and magnetic sensing. We have analysed the type of magnetic nanoparticles used in each case, their size, coating, crystal structure and the functional groups for their conjugation with biomolecules. We have also taken into account the analytical characteristics and the type of transduction. Magnetic LFIA have been used for the determination of biomarkers, pathogens, toxins, allergens and drugs. Nanocomposites have been developed as alternative to MNP with the purpose of sensitivity enhancement. Moreover, IMS in combination with other detection principles could also improve sensitivity and limit of detection. The critical analysis in this review could have an impact for the future development of magnetic LFIA in fields requiring both rapid separation and quantification.", "qid": 6, "docid": "lyw3en42", "rank": 64, "score": 7.815700054168701}, {"content": "Title: Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-\u00ce\u00b3 Content: Background: Currently, effective vaccines or specific therapeutic agents against COVID-19 are not available. However, in China, traditional Chinese herbal medicines have provided therapeutic benefit to patients with COVID-19. Jinhua Qinggan granule (JHQGG) is a Chinese multi-herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for patients clinically suspected of COVID-19 during medical observation. However, the immunological mechanism for the efficacy of JHQGG has not been confirmed. Objectives: We thus examined whether the administration of JHQGG affects hematological and immunological measures in healthy individuals. Method: We enrolled 18 healthy volunteers, all of whom tested negative for antibodies to SARS-CoV-2. Peripheral blood samples were collected 1 h after oral administration of JHQGG and subjected to hematological, biochemical, and cytokine tests. Results: JHQGG rapidly induced a significant decrease in the plasma level of IL-6 and an increase in the plasma level of IFN-{gamma}. Conclusions: Our finding suggests that the therapeutic efficacy of JHQGG against COVID-19 is, in part, associated with its rapid immunomodulatory activity.", "qid": 6, "docid": "5lpe8hg2", "rank": 65, "score": 7.800000190734863}, {"content": "Title: Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein Content: BACKGROUND Nucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed. Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis. METHODS We included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard. RESULTS We developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes. 100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method. In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients. CONCLUSIONS Those findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.", "qid": 6, "docid": "5xxi33v3", "rank": 66, "score": 7.777900218963623}, {"content": "Title: Les professionnels de sant\u00e9 face \u00e0 la pand\u00e9mie de la maladie \u00e0 coronavirus (COVID-19) : quels risques pour leur sant\u00e9 mentale ?/ [Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?] Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. RESULTS: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. CONCLUSIONS: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.", "qid": 6, "docid": "c7weqc03", "rank": 67, "score": 7.770199775695801}, {"content": "Title: A Veterinary Vaccine Development Process Map to assist in the development of new vaccines Content: The UK Government recognised the importance of vaccines in the control of new emerging disease threats and in 2015 established the UK Vaccine Network to focus on specific areas of need. One of these was the understanding of what is involved in the development of a new vaccine and what are the potential bottlenecks to a rapid response in the face of an epidemic such as Ebola, MERS and more recently COVID-19. A Working Group was established to initially produce a Vaccine Development Process Map for a Human Vaccine. However, in view of the importance of animal wellbeing and the significant impact of diseases with Zoonotic potential, a similar Map has been created outlining the Veterinary Vaccine Development Process. This paper describes the production of that Map and covers the process from the generation of a Target Product Profile (TPP) through Discovery and Feasibility, and on to Product Development and Registration.", "qid": 6, "docid": "48483m5b", "rank": 68, "score": 7.760300159454346}, {"content": "Title: An update on therapeutic repurposing strategies for COVID-19 Content: The severe acute respiratory syndrome coronavirus 2, well known as COVID-19 has become the current health distress to the entire world. In the pandemic scenario the research on the rapid development of new drug molecules is highly risky and tedious process. The current COVID-19 emergency demands an urgent development of possible strategies to protect people at high risk of infection and hence the drug repurposing became an emerging approach to fight COVID-19. This review summarizes an update on various therapeutic strategies with special attention on repurposing of drugs to fight against SARS-CoV-2 worldwide. The investigation of existing drugs for new therapeutic purposes is one line of scientific research followed to develop safe and effective COVID-19 treatments. Broad-spectrum antiviral agents (BSAAs) that have been believed to be safe through testing on early phase clinical trials have been hyped as good drug repurposing candidates. Broad-spectrum antiviral drugs such as Ribavirin, Umifenovir were advised for COVID-19 treatment. Some antibiotics may be repurposed as COVID-19 treatments such as teicoplanin, oritavancin, dalbavancin, monensin and azithromycin. Ivermectin an antiparasitic is recently repurposed. Hydroxychloroquine and chloroquine, having immunomodulating effect on humans, have been shown to have antiviral activity at starting and post-entry stages of the SARS-CoV-2 infection. There is a need for global health emergency to call for a courageous, global response at the political and governmental levels. Therefore, the regulatory agencies must act swiftly to lessen any financial obstacles involving private companies and update guidelines for drug licenses by repurposing if necessary.", "qid": 6, "docid": "9idkf0i9", "rank": 69, "score": 7.755499839782715}, {"content": "Title: R\u00e9ponse aux maladies \u00e0 coronavirus 2019 (COVID-19): faits marquants de l\u2019innovation et des perc\u00e9es scientifique et technologique au Ghana Content: Abstract While more attention has been placed on scientific innovativeness and breakthroughs in the advanced countries\u2019 attempt to contain the spread and develop vaccines for the Coronavirus Diseases 2019 (COVID-19), little attention has been paid to the few but significant innovations being achieved in some African countries. This is understandable because the scientific capacity and research infrastructure of most African countries are deficient and weak compared to other regions of the world. Nevertheless, the African country of Ghana, despite its acute healthcare and scientific infrastructure deficit, is achieving some innovational and scientific breakthrough in the COVID-19 fight. Ghanaian scientist was among the first in Africa to successfully sequenced the genome of the novel coronavirus (SARS-CoV-2). The country\u2019s laboratory leading the fight has also introduced some innovative testing methods allowing the country to test a far greater scale per million than the rest of Africa. Besides, drones are being used to deliver samples to the laboratory centers for testing. Local scientists and developers have also developed rapid diagnostic test kits, ventilators, and solar-powered handwashing machines. This paper highlights Ghana\u2019s innovativeness, scientific, and technological breakthroughs achieved so far in the fight against the pandemic.", "qid": 6, "docid": "k4a11aij", "rank": 70, "score": 7.754000186920166}, {"content": "Title: Dynamics of the SARS-CoV-2 epidemic in the earliest-affected areas in Italy: 1 Mass screening for SARS-CoV-2 serological positivity (SARS-2-SCREEN). Content: Background Several municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection since the earliest stages of the epidemic. To date, 89442 confirmed cases have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection remains unknown as several affected subjects may have been asymptomatic or have presented mild disease, thus not resulting in the identified COVID-19 cases. Methods This cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence of IgG antibodies directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS). Discussion This study was developed with the desire to understand the seroprevalence of SARS-CoV-2 infection and the epidemiological transmission characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts. This study has been approved by the Ethics Committee of the University of Milan (35/2020).", "qid": 6, "docid": "wg641kli", "rank": 71, "score": 7.747300148010254}, {"content": "Title: New blood tests for antibodies could show true scale of coronavirus pandemic Content: How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease\u2014perhaps so mild they dismissed it as a cold or allergies\u2014immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests\u2014for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune\u2014is still lacking or at least not public Scientists hope that will soon change as more tests become available", "qid": 6, "docid": "ecxji8x8", "rank": 72, "score": 7.738100051879883}, {"content": "Title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings Content: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available.", "qid": 6, "docid": "lqio7l8k", "rank": 73, "score": 7.726500034332275}, {"content": "Title: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review Content: BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "qid": 6, "docid": "998lscmk", "rank": 74, "score": 7.719200134277344}, {"content": "Title: Rapid diagnosis of SARS-CoV-2 infection by detecting IgG and IgM antibodies with an immunochromatographic device: a prospective single-center study Content: Objectives: SARS-CoV-2 infection constitutes a diagnostic challenge in patients from 2-3 weeks after the onset of symptoms, due to the low positivity rate of the PCR, especially in upper respiratory samples. Serologic tests based on ELISA have been developed and evaluated as useful complements to PCR in these situations. However, there is scarce information about the usefulness of rapid tests based on immunochromatography. The aim of our study was to analyze the diagnostic performance of these rapid tests in COVID-19 pneumonia patients. Methods: We evaluated an immunochromatographic test (AllTest COV-19 IgG / IgM kit) which detects IgG and IgM antibodies. First, we performed a validation of the serologic test using serum samples from 45 healthy control patients (group 1) and 55 confirmed by PCR cases of COVID-19 (group 2) in order to establish the specificity and sensitivity, respectively. Then we prospectively employed the test in 63 patients diagnosed with pneumonia of unknown etiology that were SARS-CoV-2 negative by PCR (group 3), to establish the diagnostic performance in these patients. Results: All patients from group 1 (healthy controls) resulted negative for the serologic test (specificity = 100%). Regarding group 2 (PCR positive) patients, the median time from the onset of symptoms was 11 days and the test was positive for either IgM or IgG in 26 out of 55 patients (overall sensitivity = 47.3%). However, in those patients with 14 days or more from onset of symptoms, the sensitivity was 73.9%. Regarding group 3 patients, the median days from onset of symptoms was 17 and the test was positive in 56 out of 63 patients (88.9% positivity rate). In these group 3 patients with 14 days or more from onset of symptoms, the positivity rate was 91.1%. Conclusions: Our study shows that serologic rapid tests can be used as a complement of PCR to diagnose SARS-CoV-2 infection after 14 days from the onset of symptoms. These immunochromatographic devices could be especially useful in hospitalized patients with pneumonia of unknown etiology with 14 or more days from the onset of symptoms and in whom the PCR has been negative.", "qid": 6, "docid": "t6rs1i7b", "rank": 75, "score": 7.707099914550781}, {"content": "Title: COVID-19 Infection Diagnosis: Potential Impact of Isothermal Amplification Technology to Reduce Community Transmission of SARS-CoV-2 Content: The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop-mediated amplification (LAMP), recombinase polymerase amplification (RPA) and Nicking enzyme-assisted reaction (NEAR) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralized laboratory and prolonged turnaround time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. Interestingly, NEAR (ID NOW\u2122 COVID-19 (Abbott, IL, USA) was able to detect the virus in 5 min. More so, isothermal platforms are cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.", "qid": 6, "docid": "gi1dlail", "rank": 76, "score": 7.682000160217285}, {"content": "Title: Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data Content: SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5-74.0), and specificity of 98.0% (95%CI 95.8-99.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "qid": 6, "docid": "4ipuy7su", "rank": 77, "score": 7.661900043487549}, {"content": "Title: Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data Content: SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5\u201374.0), and specificity of 98.0% (95%CI 95.8\u201399.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "qid": 6, "docid": "tujxlve3", "rank": 78, "score": 7.661899089813232}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \"COVID 19,\" \"SARS-CoV-2,\" and \"treatment.\" All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 6, "docid": "4ehhtkfn", "rank": 79, "score": 7.657899856567383}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \u201cCOVID 19,\u201d \u201cSARS-CoV-2,\u201d and \u201ctreatment.\u201d All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Glucocorticoids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 6, "docid": "9ryu9ady", "rank": 80, "score": 7.657898902893066}, {"content": "Title: Molecular Diagnosis of COVID-19: Challenges and Research Needs Content: Molecular diagnosis of COVID-19 primarily relies on the detection of RNA of the SARS-CoV-2 virus, the causative infectious agent of the pandemic. Reverse transcription polymerase chain reaction (RT-PCR) enables sensitive detection of specific sequences of genes that encode the RNA dependent RNA polymerase (RdRP), nucleocapsid (N), envelope (E), and spike (S) proteins of the virus. Although RT-PCR tests have been widely used and many alternative assays have been developed, the current testing capacity and availability cannot meet the unprecedented global demands for rapid, reliable, and widely accessible molecular diagnosis. Challenges remain throughout the entire analytical process, from the collection and treatment of specimens to the amplification and detection of viral RNA and the validation of clinical sensitivity and specificity. We highlight the main issues surrounding molecular diagnosis of COVID-19, including false negatives from the detection of viral RNA, temporal variations of viral loads, selection and treatment of specimens, and limiting factors in detecting viral proteins. We discuss critical research needs, such as improvements in RT-PCR, development of alternative nucleic acid amplification techniques, incorporating CRISPR technology for point-of-care (POC) applications, validation of POC tests, and sequencing of viral RNA and its mutations. Improved assays are also needed for environmental surveillance or wastewater-based epidemiology, which gauges infection on the community level through analyses of viral components in the community's wastewater. Public health surveillance benefits from large-scale analyses of antibodies in serum, although the current serological tests do not quantify neutralizing antibodies. Further advances in analytical technology and research through multidisciplinary collaboration will contribute to the development of mitigation strategies, therapeutics, and vaccines. Lessons learned from molecular diagnosis of COVID-19 are valuable for better preparedness in response to other infectious diseases.", "qid": 6, "docid": "1a6d8urj", "rank": 81, "score": 7.645599842071533}, {"content": "Title: Molecular Diagnosis of COVID-19: Challenges and Research Needs Content: [Image: see text] Molecular diagnosis of COVID-19 primarily relies on the detection of RNA of the SARS-CoV-2 virus, the causative infectious agent of the pandemic. Reverse transcription polymerase chain reaction (RT-PCR) enables sensitive detection of specific sequences of genes that encode the RNA dependent RNA polymerase (RdRP), nucleocapsid (N), envelope (E), and spike (S) proteins of the virus. Although RT-PCR tests have been widely used and many alternative assays have been developed, the current testing capacity and availability cannot meet the unprecedented global demands for rapid, reliable, and widely accessible molecular diagnosis. Challenges remain throughout the entire analytical process, from the collection and treatment of specimens to the amplification and detection of viral RNA and the validation of clinical sensitivity and specificity. We highlight the main issues surrounding molecular diagnosis of COVID-19, including false negatives from the detection of viral RNA, temporal variations of viral loads, selection and treatment of specimens, and limiting factors in detecting viral proteins. We discuss critical research needs, such as improvements in RT-PCR, development of alternative nucleic acid amplification techniques, incorporating CRISPR technology for point-of-care (POC) applications, validation of POC tests, and sequencing of viral RNA and its mutations. Improved assays are also needed for environmental surveillance or wastewater-based epidemiology, which gauges infection on the community level through analyses of viral components in the community\u2019s wastewater. Public health surveillance benefits from large-scale analyses of antibodies in serum, although the current serological tests do not quantify neutralizing antibodies. Further advances in analytical technology and research through multidisciplinary collaboration will contribute to the development of mitigation strategies, therapeutics, and vaccines. Lessons learned from molecular diagnosis of COVID-19 are valuable for better preparedness in response to other infectious diseases.", "qid": 6, "docid": "ygcksgpg", "rank": 82, "score": 7.645598888397217}, {"content": "Title: Cons\u00e9quences psychopathologiques du confinement./ [Psychopathological consequences of confinement] Content: The psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic approaches already in place, such as telemedicine, which is undergoing rapid development during the COVID-19 crisis.", "qid": 6, "docid": "vu0cevon", "rank": 83, "score": 7.638500213623047}, {"content": "Title: Research co-design in health: a rapid overview of reviews. Content: BACKGROUND Billions of dollars are lost annually in health research that fails to create meaningful benefits for patients. Engaging in research co-design - the meaningful involvement of end-users in research - may help address this research waste. This rapid overview of reviews addressed three related questions, namely (1) what approaches to research co-design exist in health settings? (2) What activities do these research co-design approaches involve? (3) What do we know about the effectiveness of existing research co-design approaches? The review focused on the study planning phase of research, defined as the point up to which the research question and study design are finalised. METHODS Reviews of research co-design were systematically identified using a rapid overview of reviews approach (PROSPERO: CRD42019123034). The search strategy encompassed three academic databases, three grey literature databases, and a hand-search of the journal Research Involvement and Engagement. Two reviewers independently conducted the screening and data extraction and resolved disagreements through discussion. Disputes were resolved through discussion with a senior author (PB). One reviewer performed quality assessment. The results were narratively synthesised. RESULTS A total of 26 records (reporting on 23 reviews) met the inclusion criteria. Reviews varied widely in their application of 'research co-design' and their application contexts, scope and theoretical foci. The research co-design approaches identified involved interactions with end-users outside of study planning, such as recruitment and dissemination. Activities involved in research co-design included focus groups, interviews and surveys. The effectiveness of research co-design has rarely been evaluated empirically or experimentally; however, qualitative exploration has described the positive and negative outcomes associated with co-design. The research provided many recommendations for conducting research co-design, including training participating end-users in research skills, having regular communication between researchers and end-users, setting clear end-user expectations, and assigning set roles to all parties involved in co-design. CONCLUSIONS Research co-design appears to be widely used but seldom described or evaluated in detail. Though it has rarely been tested empirically or experimentally, existing research suggests that it can benefit researchers, practitioners, research processes and research outcomes. Realising the potential of research co-design may require the development of clearer and more consistent terminology, better reporting of the activities involved and better evaluation.", "qid": 6, "docid": "cd845zuh", "rank": 84, "score": 7.633399963378906}, {"content": "Title: Laboratory Testing Methods for Novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Content: Following the first reports of coronavirus disease-19 (COVID-19) by China to the World Health Organization (WHO) on 31st December 2019, more than 4,302,774 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cases have been reported by authorities in 212 countries and territories by 12th May 2020. The outbreak and spread of COVID-19 worldwide, highlights the critical need for developing rapid and accurate diagnostic testing methods for emerging human coronavirus (CoV) infections. Testing is crucial to track the spread of disease during a pandemic, and to swiftly permit public health interventions including isolation, quarantine, and appropriate clinical management of afflicted individuals. The key components of viral diagnostic tests are (1) collection of the appropriate sample (blood, nasal swab, and throat swab), (2) availability of the genetic and proteomic sequences of the novel virus for analysis, and (3) rapid and accurate laboratory testing methods. The current gold standard for the molecular diagnosis of SARS-CoV-2 infection is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the qualitative and quantitative detection of viral nucleic acids. Other relevant laboratory methods include enzyme-linked immunoassays (EIA) for viral antibody and antigen detection, and serum viral neutralization (SVN) assays for antibody neutralization determination. The challenges faced in developing a diagnostic test for a novel pathogen are the ability to measure low viral loads for early detection, to provide low or no cross-reactivity with other viral strains and to deliver results rapidly. Several point-of-care molecular devices are currently being integrated for fast and accurate diagnosis of SARS-CoV-2 infections. This review discusses the current laboratory methods available to test for coronaviruses by focusing on the present COVID-19 outbreak.", "qid": 6, "docid": "401tisd3", "rank": 85, "score": 7.630000114440918}, {"content": "Title: COVID\u201019: impact on colorectal surgery Content: AIM: The rapid spread of the COVID\u201019 pandemic has created unprecedented challenges for the medical and surgical healthcare systems. With the ongoing need for urgent and emergency colorectal surgery, including surgery for colorectal cancer, several questions pertaining to operating room (OR) utilization and techniques needed to be rapidly addressed. METHOD: This manuscript discusses knowledge related to the critical considerations of patient and caregiver safety relating to personal protective equipment (PPE) and the operating room environment. RESULTS: During the COVID\u201019 pandemic, additional personal protective equipment (PPE) may be required contingent upon local availability of COVID\u201019 testing and the incidence of known COVID\u201019 infection in the respective community. In addition to standard COVID\u201019 PPE precautions, a negative\u2010pressure environment, including an OR, has been recommended, especially for the performance of aerosol\u2010generating procedures (AGPs). Hospital spaces ranging from patient wards to ORs to endoscopy rooms have been successfully converted from standard positive\u2010pressure to negative\u2010pressure spaces. Another important consideration is the method of surgical access; specifically, minimally invasive surgery with pneumoperitoneum is an AGP and thus must be carefully considered. Current debate centres around whether it should be avoided in patients known to be infected with SARS\u2010CoV\u20102 or whether it can be performed under precautions with safety measures in place to minimize exposure to aerosolized virus particles. Several important lessons learned from pressurized intraperitoneal aerosolized chemotherapy procedures are demonstrated to help improve our understanding and management. CONCLUSION: This paper evaluates the issues surrounding these challenges including the OR environment and AGPs which are germane to surgical practices around the world. Although there is no single universally agreed upon set of answers, we have presented what we think is a balanced cogent description of logical safe approaches to colorectal surgery during the COVID\u201019 pandemic.", "qid": 6, "docid": "vc4ow28n", "rank": 86, "score": 7.621200084686279}, {"content": "Title: COVID-19: impact on colorectal surgery Content: AIM: The rapid spread of the COVID-19 pandemic has created unprecedented challenges for the medical and surgical healthcare systems. With the ongoing need for urgent and emergency colorectal surgery, including surgery for colorectal cancer, several questions pertaining to operating room (OR) utilization and techniques needed to be rapidly addressed. METHOD: This manuscript discusses knowledge related to the critical considerations of patient and caregiver safety relating to personal protective equipment (PPE) and the operating room environment. RESULTS: During the COVID-19 pandemic, additional personal protective equipment (PPE) may be required contingent upon local availability of COVID-19 testing and the incidence of known COVID-19 infection in the respective community. In addition to standard COVID-19 PPE precautions, a negative-pressure environment, including an OR, has been recommended, especially for the performance of aerosol-generating procedures (AGPs). Hospital spaces ranging from patient wards to ORs to endoscopy rooms have been successfully converted from standard positive-pressure to negative-pressure spaces. Another important consideration is the method of surgical access; specifically, minimally invasive surgery with pneumoperitoneum is an AGP and thus must be carefully considered. Current debate centres around whether it should be avoided in patients known to be infected with SARS-CoV-2 or whether it can be performed under precautions with safety measures in place to minimize exposure to aerosolized virus particles. Several important lessons learned from pressurized intraperitoneal aerosolized chemotherapy procedures are demonstrated to help improve our understanding and management. CONCLUSION: This paper evaluates the issues surrounding these challenges including the OR environment and AGPs which are germane to surgical practices around the world. Although there is no single universally agreed upon set of answers, we have presented what we think is a balanced cogent description of logical safe approaches to colorectal surgery during the COVID-19 pandemic.", "qid": 6, "docid": "ydtgid63", "rank": 87, "score": 7.621199131011963}, {"content": "Title: The United States badly bungled coronavirus testing\u2014but things may soon improve ;Science ;AAAS Content: Speed is critical in the response to COVID-19 So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? The World Health Organization (WHO) has shipped testing kits to 57 countries China had five commercial tests on the market 1 month ago and can now do up to 1 6 million tests a week;South Korea has tested 65,000 people so far The U S Centers for Disease Control and Prevention (CDC), in contrast, has done only 459 tests since the epidemic began The rollout of a CDC-designed test kit to state and local labs has become a fiasco because it contained a faulty reagent Labs around the country eager to test more suspected cases\u2014and test them faster\u2014have been unable to do so No commercial or state labs have the approval to use their own tests In what is already an infamous snafu, CDC initially refused a request to test a patient in Northern California who turned out to be the first probable COVID19 case without known links to an infected person", "qid": 6, "docid": "lxjhz079", "rank": 88, "score": 7.62060022354126}, {"content": "Title: People Behavior Changes in China during COVID-19 Pandemic Content: While most countries implemented measures to reduce people activities and gathering to contain the coronavirus, the outcome may vary significantly depending on how and to what extent people behaviors have been changed. We conducted a survey of 1,048 people in five major cities in China to track and quantify the behavior changes in different periods since the outbreak. It is found that there was nearly 80% reduction of out-of-home activities (working, eating, shopping, taking public transportation, and travelling) during the peak period. Such activities are gradually increasing after the easing of containment measures but still significantly below pre-outbreak level. The significant behavior changes have contributed to the rapid control of virus transmission in China. While countries are reopening the economies before the virus disappears, the system and capacity of testing and contact tracing should be carefully designed with the tracking of people behavior changes in the future.", "qid": 6, "docid": "xrglwbgn", "rank": 89, "score": 7.619500160217285}, {"content": "Title: Head-to-head comparison of four antigen-based rapid detection tests for the diagnosis of SARS-CoV-2 in respiratory samples Content: In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We compared the performance of four rapid antigen detection tests for SARS-CoV-2 in respiratory samples. Immunochromatographic SARS-CoV-2 assays from RapiGEN, Liming bio, Savant, and Bioeasy were evaluated using universal transport medium containing naso-oropharyngeal swabs from suspected Covid-19 cases. The diagnostic accuracy was determined in comparison to SARS-CoV-2 RT-PCR. A total of 111 samples were included; 80 were RT-PCR positive. Median patients\u2019 age was 40 years, 55% were female, and 88% presented within the first week after symptom onset. The evaluation of the Liming bio assay was discontinued due to insufficient performance. The overall sensitivity values of RapiGEN, Liming bio, and Bioeasy tests were 62.0% (CI95% 51.0\u201371.9), 16.7% (CI95% 10.0\u201326.5), and 85.0% (CI95% 75.6\u201391.2), respectively, with specificities of 100%. Sensitivity was significantly higher in samples with high viral loads (RapiGEN, 84.9%; Bioeasy, 100%). The study highlighted the significant heterogeneity of test performance among evaluated assays, which might have been influenced by the use of a non-validated sample material. The high sensitivity of some tests demonstrated that rapid antigen detection has the potential to serve as an alternative diagnostic method, especially in patients presenting with high viral loads in early phases of infection. This is particularly important in situations with limited access to RT-PCR or prolonged turnaround time. Further comparative evaluations are necessary to select products with high performance among the growing market of diagnostic tests for SARS-CoV-2.", "qid": 6, "docid": "3taykdr1", "rank": 90, "score": 7.587299823760986}, {"content": "Title: Covid-19 rapid test by combining a random forest based web system and blood tests Content: The disease caused by the new type of coronavirus, the Covid-19, has posed major public health challenges for many countries. With its rapid spread, since the beginning of the outbreak in December 2019, the disease transmitted by SARS-Cov2 has already caused over 400 thousand deaths to date. The diagnosis of the disease has an important role in combating Covid-19. Proposed method In this work, we propose a web system, Heg.IA, which seeks to optimize the diagnosis of Covid-19 through the use of artificial intelligence. The main ideia is that healthcare professionals can insert 41 hematological parameters from common blood tests and arterial gasometry into the system. Then, Heg.IA will provide a diagnostic report. It will indicate if the patient is infected with SARS-Cov2 virus, and also predict the type of hospitalization (regular ward, semi-ICU, or ICU). We developed a web system called Heg.IA to support decision-making regarding to diagnosis of Covid-19 and to the indication of hospitalization on regular ward, semi-ICU or ICU. This application is based on decision trees in a Random Forest architecture with 90 trees. The system showed to be highly efficient, with great results for both Covid-19 diagnosis and to recommend hospitalization. For the first scenario we found average results of accuracy of 92.891% {+/-} 0.851, kappa index of 0.858 {+/-} 0.017, sensitivity of 0.936 {+/-} 0.011, precision of 0.923 {+/-} 0.011, specificity of 0.921 {+/-} 0.012 and area under ROC of 0.984 {+/-} 0.003. As for the indication of hospitalization, we achieved excellent performance of accuracies above 99% and more than 0.99 for the other metrics in all situations. By using a computationally simple method, based on the classical decision trees, we were able to achieve high diagnosis performance. Heg.IA system may be a way to overcome the testing unavailability in the context of Covid-19. We also expect the system will provide wide access to Covid-19 effective diagnosis and thereby reach and help saving lives.", "qid": 6, "docid": "wdithqgh", "rank": 91, "score": 7.585299968719482}, {"content": "Title: Is the turtle still plodding along? Public management reform in Germany Content: Public management reforms in Germany have long been characterized by slow-moving incrementalism and maintenance of its administrative system\u2019s central characteristics. This article reviews recent developments in administrative reforms against the background of the traditional German reform style. More ambitious reform efforts in the field of digitalization raise conceptual puzzles related to the conditions under which incrementalism can generate substantive change\u2013and at what point incremental reforms give way to more rapid patterns of change. The article also discusses the implications of the ongoing COVID-19 crisis on public management reforms.", "qid": 6, "docid": "k93q3i3i", "rank": 92, "score": 7.56820011138916}, {"content": "Title: Cons\u00e9quences psychopathologiques du confinement Content: Abstract The psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. As with domestic violence, we need to look for these symptoms in order to enable management. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic approaches already in place, such as telemedicine, which is undergoing rapid development during the COVID-19 crisis.", "qid": 6, "docid": "vudufbi0", "rank": 93, "score": 7.562900066375732}, {"content": "Title: Evaluation of the commercially available LightMix\u00ae Modular E-gene kit using clinical and proficiency testing specimens for SARS-CoV-2 detection Content: BACKGROUND: Rapid and sensitive diagnostic assays for SARS-CoV-2 detection are required for prompt patient management and infection control. The analytical and clinical performances of LightMix\u00ae Modular SARS and Wuhan CoV E-gene kit, a widely used commercial assay for SARS-CoV-2 detection, have not been well studied. OBJECTIVE: To evaluate the performance characteristics of the LightMix\u00ae E-gene kit in comparison with well-validated in-house developed COVID-19 RT-PCR assays. STUDY DESIGN: Serial dilutions of SARS-CoV-2 culture isolate extracts were used for analytical sensitivity evaluation. A total of 289 clinical specimens from 186 patients with suspected COVID-19 and 8 proficiency testing (PT) samples were used to evaluate the diagnostic performance of the LightMix\u00ae E-gene kit against in-house developed COVID-19-RdRp/Hel and COVID-19-N RT-PCR assays. RESULTS: The LightMix\u00ae E-gene kit had a limit of detection of 1.8\u00e2\u0080\u00af\u00d7\u00e2\u0080\u00af10-1 TCID50/mL, which was one log10 lower than those of the two in-house RT-PCR assays. The LightMix\u00ae E-gene kit (149/289 [51.6%]) had similar sensitivity as the in-house assays (144/289 [49.8%] for RdRp/Hel and 146/289 [50.5%] for N). All three assays gave correct results for all the PT samples. Cycle threshold (Cp) values of the LightMix\u00ae E-gene kit and in-house assays showed excellent correlation. Reproducibility of the Cp values was satisfactory with intra- and inter-assay coefficient of variation values <5%. Importantly, the LightMix\u00ae E-gene kit, when used as a stand-alone assay, was equally sensitive as testing algorithms using multiple COVID-19 RT-PCR assays. CONCLUSIONS: The LightMix\u00ae E-gene kit is a rapid and sensitive assay for SARS-CoV-2 detection. It has fewer verification requirements compared to laboratory-developed tests.", "qid": 6, "docid": "rizomg5m", "rank": 94, "score": 7.55620002746582}, {"content": "Title: The 2019-2020 novel coronavirus (severe acute respiratory syndrome coronavirus 2) pandemic: A joint american college of academic international medicine-world academic council of emergency medicine multidisciplinary COVID-19 working group consensus paper Content: What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a 'new normal' are discussed in this article.", "qid": 6, "docid": "o1yfuwoy", "rank": 95, "score": 7.543799877166748}, {"content": "Title: Prevalence of IgG and IgM antibodies to SARS-CoV-2 among clinic staff and patients Content: The coronavirus disease 2019 (COVID-19) is now a pandemic with devastating social and economic consequences. The extent of the spread of COVID-19 within populations is uncertain since diagnostic tests have not been carried out on all eligible persons and doing such diagnostic tests on everyone is much less feasible in developing countries such as Nigeria. Tests for antibodies to SARS-CoV-2, the virus that causes COVID-19, are more affordable, readily available, and require minimal training than current diagnostic tests. Employing a seroepidemiological strategy, serological tests were conducted on 66 volunteering staff and patients at the University of Calabar Teaching Hospital (UCTH), a Federal Government owned tertiary healthcare facility, to determine the extent of exposure to SARS-CoV-2, from 17th to 25th June 2020. Using a COVID-19 IgG/IgM Rapid Test Cassette with emergency use authorization (EUA) from the Food and Drug Administration (FDA) of the United States, it was observed that of the 66 samples tested, 5 (7.6%) were both IgG and IgM positive and 17 (26%) were IgG positive. Moreover, for 44 of the 66 participants, simultaneous tests were carried out using a rapid test kit from a different manufacturer but without FDA-EUA and all the results completely matched with the FDA-EUA kit, except one case where the FDA-EUA kit showed positive for both IgG and IgM while the other kit was positive only for IgM. The 26% positive IgG indicates a high exposure rate for the hospital staff and patients and points to community transmission where the facility is situated. Hence, immediate activation of WHO guidelines for controlling community transmission is called for. These results can further serve as a pilot study to guide public health policies in response to COVID-19 pandemic in both the general population and in healthcare settings.", "qid": 6, "docid": "3s6ytfkk", "rank": 96, "score": 7.535900115966797}, {"content": "Title: In bid to rapidly expand coronavirus testing, U.S. agency abruptly changes rules ;Science ;AAAS Content: The Food and Drug Administration (FDA) today recommended a dramatic shift in how it implements regulations that control whether laboratories can use diagnostic kits created in-house to test for infections of coronavirus-2019 (COVID-19) \u201cWe issued a policy this morning that allows us to have a lot of flexibility around the development of diagnostic tests,\u201d said FDA Commissioner Stephen Hahn at a White House briefing with President Donald Trump this afternoon \u201cWe expect this policy to have a significant impact \u201d The change could greatly expand the number of laboratories able to do coronavirus testing The U S government has come under severe criticism for not providing nearly enough tests needed to understand the extent of spread in the population A test kit produced and distributed by the U S Centers for Disease Control and Prevention (CDC) was shelved after state and local lab trying it out discovered that it contained a faulty reagent As a result, many labs that have the capability to test themselves have not been allowed to do so The new recommendations focus on \u201chigh-complexity testing laboratories\u201d that are certified under federal rules known as Clinical Laboratory Improvement Amendments This group of facilities includes many hospital labs, like the one that epidemiologist Michael Mina works at Brigham and Women\u2019s Hospital in Boston \u201cEssentially it\u2019s opening up a clear and concise avenue for labs like the one at Brigham and Women\u2019s,\u201d says Mina \u201cIt\u2019s what I\u2019ve been advocating for a month now \u201d", "qid": 6, "docid": "jsbdmnx5", "rank": 97, "score": 7.534800052642822}, {"content": "Title: The connection of growth and medication of COVID-19 affected people after 30 days of lock down in India Content: The COVID-19 pandemic has already consumed few months of indolence all over the world. Almost every part of the world from which the victim of COVID 19 are, have not yet been able to find out a strong way to combat corona virus. Therefore, the main aim is to minimize the spreading of the COVID-19 by detecting most of the affected people during lockdown. Hence, it is necessary to understand what the nature of growth is of spreading of this corona virus with time after almost one month (30 days) of lockdown. In this paper we have developed a very simple mathematical model to describe the growth of spreading of corona virus in human being. This model is based on realistic fact and the statistics we have so far. For controlling the spread of the COVID-19, minimization of the growth with minimum number of days of lockdown is necessary. We have established a relation between the long-term recovery coefficient and the long-term infected coefficient. The growth can be minimized if such condition satisfies. We have also discussed how the different age of the people can be cured by applying different types of medicine. We have presented the data of new cases, recovery and deaths per day to visualize the different coefficient for India and establish our theory. We have also explained how the medicine could be effective to sustain and improve such condition for country having large population like India.", "qid": 6, "docid": "bj12pp9d", "rank": 98, "score": 7.51230001449585}, {"content": "Title: Low-cost measurement of facemask efficacy for filtering expelled droplets during speech Content: Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have applied a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. We compare a variety of commonly available mask types and observe that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Our measurement setup is inexpensive and can be built and operated by non-experts, allowing for rapid evaluation of mask performance during speech, sneezing, or coughing.", "qid": 6, "docid": "oyxxji7r", "rank": 99, "score": 7.50600004196167}, {"content": "Title: Development of a rapid test kit for SARS-CoV-2: an example of product design Content: We present an example of applying 'need-driven' product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.", "qid": 6, "docid": "52pw2vwx", "rank": 100, "score": 7.475800037384033}]}
{"query": "are there serological tests that detect antibodies to coronavirus?", "hits": [{"content": "Title: Establishment of serological test to detect antibody against ferret coronavirus Content: Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1\u2013179 and a.a. 180\u2013374 of the N protein, but two serum samples did not a.a. 180\u2013374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1\u2013179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1\u2013179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection.", "qid": 7, "docid": "3g75spkc", "rank": 1, "score": 10.271200180053711}, {"content": "Title: Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus-2: A Narrative Review Content: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "qid": 7, "docid": "01mo6yo9", "rank": 2, "score": 10.224900245666504}, {"content": "Title: Serodiagnostics for Severe Acute Respiratory Syndrome\u2013Related Coronavirus-2: A Narrative Review Content: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome\u2013related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "qid": 7, "docid": "ofd2ipvs", "rank": 3, "score": 10.224899291992188}, {"content": "Title: Immunological assays for SARS-CoV-2: an analysis of available commercial tests to measure antigen and antibodies Content: The rapid spread of SARS-CoV-2 coronavirus infection has led to the development of molecular and serologic tests in a short period of time. While tests such as RT-PCR have applications in the immediate diagnosis revealing the presence of the virus, serological tests can be used to determine previous exposure to the virus and complement acute diagnosis. Antibody production can occur as early as 5 days post-infection. Both IgM and IgG specific anti-SARS-COV-2 antibodies can be a useful tool to test faster and larger groups of individuals. The objective of this study was to carry out a review of the different serological tests offered to detect antigen or antibodies against SARS-CoV-2. This information should be useful for decision takers in different countries to choose a test according to their needs. Based on web pages that listed serological assays, we found 226 coming from 20 countries, the majority are indirect tests for specific antibodies detection (n 180) and use immunochromatography methods (n 110) with samples coming from blood-derived products (n 105). Measuring IgM/IgG at the same time (n 112) and a procedure time of <20 min (n 83) are the most common. The overall average sensitivity was 91.8% and specificity was 97%. Most of the tests are currently for in vitro diagnosis (IVD). This information gathered could change day by day due to the expedite process of production and emergency of authorization use.", "qid": 7, "docid": "qjma4rsp", "rank": 4, "score": 9.97439956665039}, {"content": "Title: In vitro diagnostics of coronavirus disease 2019: technologies and application Content: Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "qid": 7, "docid": "923jpec0", "rank": 5, "score": 9.97350025177002}, {"content": "Title: In vitro diagnostics of coronavirus disease 2019: Technologies and application Content: Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "qid": 7, "docid": "r1yf75bo", "rank": 6, "score": 9.973499298095703}, {"content": "Title: Reliability of serological tests for COVID-19: Comparison of three immunochromatography test kits for SARS-CoV-2 antibodies. Content: Background: Several immunochromatographic serological test kits have been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies, but their relative performance and potential clinical utility is unclear. Methods: Three commercially available serological test kits were evaluated using 99 serum samples collected from 29 patients diagnosed with coronavirus disease 2019 (COVID-19). Results: The IgM antibody-positive rates of the three serological test kits for samples taken at the early stage of the disease (0-6 days after onset) were 19.0%, 23.8%, and 19.0%, respectively. The IgM antibody-positive rates over the entire period were 21.2%, 60.6%, and 15.2%, respectively. The IgG antibody-positive rates for samples taken after 13 days of onset were 100.0%, 97.6%, and 97.6%, respectively. Conclusion: There were large differences among the results of the three test kits. Only few cases showed positive results for IgM in the early stage of disease and the IgM antibody-positive rates over the entire period were low, suggesting that the kits used in this study were unsuitable for diagnosis of COVID-19. The IgG antibody was positive in almost all samples after 13 days of onset, suggesting that it may be useful for determining infections in the recent past.", "qid": 7, "docid": "fn9t38as", "rank": 7, "score": 9.910799980163574}, {"content": "Title: Review of Current Advances in Serologic Testing for COVID-19 Content: OBJECTIVES: To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. RESULTS: The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. CONCLUSIONS: The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation.", "qid": 7, "docid": "77rcr30x", "rank": 8, "score": 9.847999572753906}, {"content": "Title: Serological responses in patients with severe acute respiratory syndrome coronavirus infection and cross-reactivity with human coronaviruses 229E, OC43, and NL63. Content: The serological response profile of severe acute respiratory syndrome (SARS) coronavirus (CoV) infection was defined by neutralization tests and subclass-specific immunofluorescent (IF) tests using serial sera from 20 patients. SARS CoV total immunoglobulin (Ig) (IgG, IgA, and IgM [IgGAM]) was the first antibody to be detectable. There was no difference in time to seroconversion between the patients who survived (n = 14) and those who died (n = 6). Although SARS CoV IgM was still detectable by IF tests with 8 of 11 patients at 7 months postinfection, the geometric mean titers dropped from 282 at 1 month postinfection to 19 at 7 months (P = 0.001). In contrast, neutralizing antibody and SARS CoV IgGAM and IgG antibody titers remained stable over this period. The SARS CoV antibody response was sometimes associated with an increase in preexisting IF IgG antibody titers for human coronaviruses OC43, 229E, and NL63. There was no change in IF IgG titer for virus capsid antigen from the herpesvirus that was used as an unrelated control, Epstein-Barr virus. In contrast, patients who had OC43 infections, and probably also 229E infections, without prior exposure to SARS CoV had increases of antibodies specific for the infecting virus but not for SARS CoV. There is a need for awareness of cross-reactive antibody responses between coronaviruses when interpreting IF serology.", "qid": 7, "docid": "q41plzqq", "rank": 9, "score": 9.833600044250488}, {"content": "Title: Surveillance using serological and molecular methods for the detection of infectious agents in captive Brazilian neotropic and exotic felids. Content: The aim of the current study was to investigate the exposure of captive wild felids to various infectious pathogens using serological and molecular methods. One hundred and fifty-nine neotropic felids and 51 exotic felids from 28 captive settings in Brazil were tested. While antibodies against Feline parvovirus and Feline coronavirus (FCoV), Feline calicivirus and Bartonella spp. were frequently detected by serologic tests, antibodies against Felid herpesvirus 1 or infection with hemotropic mycoplasmas were less prevalent. Serologic evidence of exposure to Ehrlichia spp., Feline immunodeficiency virus, and Feline leukemia virus (FeLV) was detected rarely, and infections with FeLV, Ehrlichia spp., and Cytauxzoon spp. were found infrequently. The detected Bartonella sequence was molecularly similar to B. koehlerae and B. henselae; for Cytauxzoon, the sequence resembled those from domestic cats. No Anaplasma phagocytophilum and Theileria spp. infections were detected. The positive test results varied significantly among different facilities and species. Additionally, FCoV seropositivity was more prevalent in captivity than in free-ranging populations. Results suggest that testing is appropriate prior to relocation of felids.", "qid": 7, "docid": "ad7pu0u7", "rank": 10, "score": 9.798199653625488}, {"content": "Title: A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients Content: Background The outbreak of the recently emerged novel corona virus disease 2019 (COVID-19) poses a challenge for public health laboratories. We aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. Methods A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 were used to screen the serums of 238 admitted hospital patients with confirmed or suspected SARS-CoV-2 infection from February 6 to February 14, 2020. SARS-CoV-2 RNA was detected by real time RT-PCR on pharyngeal swab specimens. Findings Of the 238 patients, 194 (81.5%) were detected to be antibody (IgM and/or IgG) positive, which was significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibody between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85) whose nucleic acid tests were negative. After the patients were defined to the different stages of disease based on the day when the test samples were collected, the analysis results showed that the antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped to above 80% from less than 50%. On the contrary, the positive rates of viral RNA kept above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. In addition, half of the suspected patients with symptoms for 6-10 days were detected to be antibody positive. Interpretation The suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is important for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After that, the diagnosis for viral infection should be majorly dependent on serological assay. Keywords. SARS-CoV-2; diagnosis; serological assay; nucleic acid test", "qid": 7, "docid": "qgvue8yw", "rank": 11, "score": 9.708600044250488}, {"content": "Title: A serologic survey of Oklahoma cats for antibodies to feline immunodeficiency virus, coronavirus, and Toxoplasma gondii and for antigen to feline leukemia virus. Content: A serologic survey was done on 618 cat sera submitted to the Oklahoma Animal Disease Diagnostic Laboratory between July 1, 1987 and June 30, 1988. The samples were collected from clinically normal and sick cats. The sera were tested for the presence of antibodies to feline immunodeficiency virus by a commercial immunoassay, to a coronavirus by an indirect fluorescent antibody test, and to Toxoplasma gondii by a commercial latex agglutination test and for the presence of feline leukemia virus antigen with one of 3 different commercial assay kits. Ten percent of the sera had antibodies to feline immunodeficiency virus, 35% had antibodies to a coronavirus, and 22% had antibodies to Toxoplasma gondii. Feline leukemia virus antigen was detected in 15% of the sera. Thirty-two percent of the sera had evidence of exposure to 2 or more of the agents.", "qid": 7, "docid": "tmoc5289", "rank": 12, "score": 9.682299613952637}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients Content: A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "qid": 7, "docid": "83odb66l", "rank": 13, "score": 9.675299644470215}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2\u2212Specific Antibody Responses in Coronavirus Disease Patients Content: A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein\u2013specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2\u2013infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2\u2013specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "qid": 7, "docid": "mryazbnq", "rank": 14, "score": 9.675298690795898}, {"content": "Title: Estimating seroprevalence with imperfect serological tests: exploiting cutoff-free approaches Content: Large-scale serological testing in the population is essential to determine the true extent of the current Coronavirus pandemic. Serological tests measure antibody responses against pathogens and define cutoff levels that dichotomize the quantitative test measures into sero-positives and negatives. With the imperfect tests that are currently available to test for past SARS-CoV-2 infection, the fraction of seropositive individuals in serosurveys is a biased estimator of seroprevalence and is usually corrected post-hoc to account for the sensitivity and specificity. Here we use a likelihood-based inference method \u2014 previously called mixture models \u2014 for the estimation of the seroprevalence that does not require to define cutoffs by integrating the quantitative test measures directly into the statistical inference procedure. We confirm that this likelihood-based method outperforms the methods based on cutoffs and post-hoc corrections leading to less variation in point-estimates of the seroprevalence and its temporal trend. We illustrate how the likelihood-based method can be used to optimize the design of serosurveys with imperfect serological tests. We also provide guidance on the number of control and case sera that are required to quantify the test\u2019s ambiguity sufficiently to enable the reliable estimation of the seroprevalence. Lastly, we show how this approach can be used to identify classes of case sera with an unknown distribution of quantitative test measures that have not been used for test validation. An R-package with the likelihood and power analysis functions is provided. Our study advocates to using serological tests without cutoffs, especially if they are used to determine parameters characterizing populations rather than individuals. This approach circumvents some of the shortcomings of cutoff-based methods with post-hoc correction at exactly the low seroprevalence levels and test accuracies that we are currently facing in COVID-19 serosurveys. Author Summary As other pathogens, SARS-CoV-2 elicits antibody responses in infected people that can be detected in their blood serum as early as a week after the infection until long after recovery. The presence of SARS-CoV-2 specific antibodies can therefore be used as a marker of past infection, and the prevalence of seropositive people, i.e. people with specific antibodies, is a key measure to determine the extent of the Coronavirus pandemic. The serological tests, however, are usually not perfect, yielding false positive and negative results. Here we exploit an approach that refrains from classifying people as seropositive or negative, but rather compares the antibody level to that of confirmed cases and controls. This approach leads to more reliable seroprevalence estimates, especially for the low prevalence and low test accuracies that we face during the current Coronavirus pandemic. We also show how this approach can be extended to infer the presence of cases that have not been used for validating the test, such as people that underwent a mild or even asymptomatic infection.", "qid": 7, "docid": "rko7qdqk", "rank": 15, "score": 9.626700401306152}, {"content": "Title: Development of monoclonal antibodies and serological assays including indirect ELISA and fluorescent microsphere immunoassays for diagnosis of porcine deltacoronavirus Content: BACKGROUND: A novel porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was reported in China in 2012 and identified in the U.S. in early 2014. Since then, PDCoV has been identified in a number of U.S. states and linked with clinical disease including acute diarrhea and vomiting in the absence of other identifiable pathogens. Since PDCoV was just recently linked with clinical disease, few specific antibody-based reagents were available to assist in diagnosis of PDCoV and limited serological capabilities were available to detect an antibody response to this virus. Therefore, the overall objective of this project was to develop and validate selected diagnostic reagents and assays for PDCoV antigen and antibody detection. RESULTS: The nucleoprotein of PDCoV was expressed as a recombinant protein and purified for use as an antigen to immunize mice for polyclonal, hyperimmune sera and monoclonal antibody (mAb) production. The resulting mAbs were evaluated for use in fluorescent antibody staining methods to detect PDCoV infected cells following virus isolation attempts and for immunohistochemistry staining of intestinal tissues of infected pigs. The same antigen was used to develop serological tests to detect the antibody response to PDCoV in pigs following infection. Serum samples from swine herds with recent documentation of PDCoV infection and samples from expected na\u00efve herds were used for initial assay optimization. The tests were optimized in a checkerboard fashion to reduce signal to noise ratios using samples of known status. Statistical analysis was performed to establish assay cutoff values and assess diagnostic sensitivities and specificities. At least 629 known negative serum samples and 311 known positive samples were evaluated for each assay. The enzyme linked immunosorbent assay (ELISA) showed diagnostic sensitivity (DSe) of 96.1 % and diagnostic specificity (DSp) of 96.2 %. The fluorescent microsphere immunoassay (FMIA) showed a DSe of 95.8 % and DSp of 98.1 %. Both ELISA and FMIA detected seroconversion of challenged pigs between 8\u201314 days post-infection (DPI). An indirect fluorescent antibody (IFA) test was also developed using cell culture adapted PDCoV for comparative purposes. CONCLUSION: These new, specific reagents and serological assays will allow for improved diagnosis of PDCoV. Since many aspects of PDCoV infection and transmission are still not fully understood, the reagents and assays developed in this project should provide valuable tools to help understand this disease and to aid in the control and surveillance of porcine deltacoronavirus outbreaks.", "qid": 7, "docid": "xnqkqgvy", "rank": 16, "score": 9.57859992980957}, {"content": "Title: Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity. Content: Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.", "qid": 7, "docid": "91pb9nq3", "rank": 17, "score": 9.56820011138916}, {"content": "Title: Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity Content: Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.", "qid": 7, "docid": "rgls0xgn", "rank": 18, "score": 9.568199157714844}, {"content": "Title: Development of an indirect ELISA, blocking ELISA, fluorescent microsphere immunoassay and fluorescent focus neutralization assay for serologic evaluation of exposure to North American strains of Porcine Epidemic Diarrhea Virus Content: BACKGROUND: Recent, severe outbreaks of porcine epidemic diarrhea virus (PEDV) in Asia and North America highlight the need for well-validated diagnostic tests for the identification of PEDV infected animals and evaluation of their immune status to this virus. PEDV was first detected in the U.S. in May 2013 and spread rapidly across the country. Some serological assays for PEDV have been previously described, but few were readily available in the U.S. Several U.S. laboratories quickly developed indirect fluorescent antibody (IFA) assays for the detection of antibodies to PEDV in swine serum, indicating prior exposure. However, the IFA has several disadvantages, including low throughput and relatively subjective interpretation. Different serologic test formats have advantages and disadvantages, depending on the questions being asked, so a full repertoire of tests is useful. Therefore, the objective of this study was to develop and validate multiple improved serological assays for PEDV, including an indirect ELISA (iELISA); a highly specific monoclonal antibody-based blocking ELISA (bELISA); fluorescent microsphere immunoassays (FMIA) that can be multiplexed to monitor exposure to multiple antigens and pathogens simultaneously; and a fluorescent focus neutralization assay (FFN) to measure functional virus neutralizing antibodies. RESULTS: A recombinant North American nucleoprotein (NP) based iELISA was developed and validated along with a bELISA using newly developed PEDV-NP specific biotinylated monoclonal antibodies (mAbs) and an FMIA using magnetic beads coupled with expressed NA PEDV-NP. Receiver operating characteristic (ROC) analysis was performed using swine serum samples (iELISA n = 1486, bELISA n = 1186, FMIA n = 1420). The ROC analysis for the FMIA showed estimated sensitivity and specificity of 98.2 and 99.2 %, respectively. The iELISA and bELISA showed a sensitivity and specificity of 97.9 and 97.6 %; and 98.2 and 98.9 %, respectively. Inter-rater (kappa) agreement was calculated to be 0.941 between iELISA and IFA, 0.945 between bELISA and IFA and 0.932 between FMIA and IFA. Similar comparative kappa values were observed between the iELISA, bELISA and FMIA, which demonstrated a significant level of testing agreement among the three assays. No cross-reactivity with the closely related coronaviruses, transmissible gastroenteritis virus (TGEV) or porcine respiratory coronavirus (PRCV) was noted with these assays. All three assays detected seroconversion of na\u00efve animals within 6\u20139 days post exposure. The FFN assay allows relative quantitation of functional neutralizing antibodies in serum, milk or colostrum samples. CONCLUSION: Well-validated iELISA, bELISA and FMIA assays for the detection of PEDV antibodies were developed and showed good correlation with IFA and each other. Each assay format has advantages that dictate how they will be used in the field. Newly developed mAbs to the PEDV-NP were used in the bELISA and for expediting FFN testing in the detection and quantitation of neutralizing antibodies. In addition, these PEDV mAbs are useful for immunohistochemistry, fluorescent antibody staining and other antigen-based tests. Measurement of neutralizing antibody responses using the FFN assay may provide a valuable tool for assessment of vaccine candidates or protective immunity.", "qid": 7, "docid": "6alsigxk", "rank": 19, "score": 9.4822998046875}, {"content": "Title: COVID-19 Special Column: Principles Behind the Technology for Detecting SARS-CoV-2, the Cause of COVID-19. Content: Nationwide shortages of tests that detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and diagnose coronavirus disease 2019 (COVID-19) have led the US Food and Drug Administration (FDA) to significantly relax regulations regarding COVID-19 diagnostic testing. To date the FDA has given emergency use authorization (EUA) to 48 COVID-19 in vitro diagnostic tests and 21 high complexity molecular-based laboratory developed tests, as well as implemented policies that give broad authority to clinical laboratories and commercial manufacturers in the development, distribution, and use of COVID-19 diagnostic tests. Currently, there are 2 types of diagnostic tests available for the detection of SARS-CoV-2: (1) molecular and (2) serological tests. Molecular detection of nucleic acid (RNA or DNA) sequences relating to the suspected pathogen is indicative of an active infection with the suspected pathogen. Serological tests detect antibodies against the suspected pathogen, which are produced by an individual's immune system. A positive serological test result indicates recent exposure to the suspected pathogen but cannot be used to determine if the individual is actively infected with the pathogen or immune to reinfection. In this article, the SARS-CoV-2 diagnostic tests currently approved by the FDA under EUA are reviewed, and other diagnostic tests that researchers are developing to detect SARS-CoV-2 infection are discussed.", "qid": 7, "docid": "8hrjgcas", "rank": 20, "score": 9.469200134277344}, {"content": "Title: COVID-19 Special Column: Principles Behind the Technology for Detecting SARS-CoV-2, the Cause of COVID-19 Content: Nationwide shortages of tests that detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and diagnose coronavirus disease 2019 (COVID-19) have led the US Food and Drug Administration (FDA) to significantly relax regulations regarding COVID-19 diagnostic testing. To date the FDA has given emergency use authorization (EUA) to 48 COVID-19 in vitro diagnostic tests and 21 high complexity molecular-based laboratory developed tests, as well as implemented policies that give broad authority to clinical laboratories and commercial manufacturers in the development, distribution, and use of COVID-19 diagnostic tests. Currently, there are 2 types of diagnostic tests available for the detection of SARS-CoV-2: (1) molecular and (2) serological tests. Molecular detection of nucleic acid (RNA or DNA) sequences relating to the suspected pathogen is indicative of an active infection with the suspected pathogen. Serological tests detect antibodies against the suspected pathogen, which are produced by an individual's immune system. A positive serological test result indicates recent exposure to the suspected pathogen but cannot be used to determine if the individual is actively infected with the pathogen or immune to reinfection. In this article, the SARS-CoV-2 diagnostic tests currently approved by the FDA under EUA are reviewed, and other diagnostic tests that researchers are developing to detect SARS-CoV-2 infection are discussed.", "qid": 7, "docid": "q2b4ig1h", "rank": 21, "score": 9.469199180603027}, {"content": "Title: Serological assays for emerging coronaviruses: Challenges and pitfalls Content: Abstract More than a decade after the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002/2003 the occurrence of a novel CoV termed Middle East respiratory syndrome (MERS) CoV challenges researchers and public health authorities. To control spread and finally contain novel viruses, rapid identification and subsequent isolation of infected individuals and their contacts is of utmost importance. Next to methods for nucleic acid detection, validated serological assays are particularly important as the timeframe for antibody detection is less restricted. During the SARS-CoV epidemic a wide variety of serological diagnostic assays were established using multiple methods as well as different viral antigens. Even though the majority of the developed assays showed high sensitivity and specificity, numerous studies reported on cross-reactive antibodies to antigens from wide-spread common cold associated CoVs. In order to improve preparedness and responsiveness during future outbreaks of novel CoVs, information and problems regarding serological diagnosis that occurred during the SARS-CoV should be acknowledged. In this review we summarize the performance of different serological assays as well as the applicability of the two main applied antigens (spike and nucleocapsid protein) used during the SARS-CoV outbreak. We highlight challenges and potential pitfalls that occur when dealing with a novel emerging coronavirus like MERS-CoV. In addition we describe problems that might occur when animal sera are tested in serological assays for the identification of putative reservoirs. Finally, we give a recommendation for a serological testing scheme and outline necessary improvements that should be implemented for a better preparedness.", "qid": 7, "docid": "nna0s5mf", "rank": 22, "score": 9.467599868774414}, {"content": "Title: Development of a competitive enzyme-linked immunosorbent assay for detection of turkey coronavirus antibodies. Content: A competitive enzyme-linked immunosorbent assay (cELISA) was developed for detection of turkey coronavirus (TCV) antibodies. The cELISA utilized a recombinant baculovirus (Autographa californica nuclear polyhedrosis virus)-expressed TCV nucleocapsid (N) protein and biotin-labeled TCV N protein-specific monoclonal antibody. Sensitivity and specificity of the cELISA for detection of TCV antibodies were determined by comparison with the indirect fluorescent antibody test (IFAT) with 1269 reference, experimentally derived, and field-origin sera. Sera with discordant cELISA and IFAT results were further evaluated by western immunoblot analyses. The cELISA detected antibodies specific for TCV and infectious bronchitis virus, a closely related coronavirus, but did not detect antibodies specific for other avian viruses. A high degree of concordance was observed between the cELISA and IFAT; sensitivity and specificity of the cELISA relative to IFAT were 92.9% and 96.2%, respectively. Western immunoblot analyses provided additional evidence of cELISA specificity. The findings indicate that the cELISA is a rapid, sensitive, and specific serologic test for detection of TCV antibodies in turkeys.", "qid": 7, "docid": "wlqk3hht", "rank": 23, "score": 9.458800315856934}, {"content": "Title: Use of recombinant nucleocapsid proteins for serological diagnosis of feline coronavirus infection by three immunochromatographic tests Content: Abstract Three types of immunochromatographic assays (ICAs) were designed to detect anti-feline coronavirus (FCoV) antibodies. Recombinant FCoV nucleocapsid protein (rNP) was used as a conjugate or test line in all 3 ICA kits (CJIgG/TNP, CJNP/TNP, and CJNP/TPA). All three ICA kits were capable of detecting anti-FCoV antibodies; however, non-specific positive reactions of anti-FCoV antibody-negative plasma samples with the test line were observed in 2 ICA kits (CJIgG/TNP and CJNP/TNP), in which rNP was used as the test line. On the other hand, the specific detection of anti-FCoV antibodies was possible in all plasma, serum, whole blood, and ascitic fluid samples using the ICA kit with protein A blotted as the test line (CJNP/TPA). In addition, the specificity and sensitivity of ICA (CJNP/TPA) were equivalent to those of the reference ELISA. The development of simple antibody test methods using the principle of ICA (CJNP/TPA) for other coronavirus and feline viral infections is expected in the future.", "qid": 7, "docid": "k6wkpmpn", "rank": 24, "score": 9.450900077819824}, {"content": "Title: The Role of Antibody Testing for SARS-CoV-2: Is There One? Content: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of both molecular and serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 molecular tests, submission for EUA is currently a voluntary process for manufacturers of serologic assays. The absence of FDA oversight of serologic tests is concerning, given that the commercially available serologic assays are highly variable, differing in their format, the antibody class detected, the targeted antigen and the acceptable specimen types. An added complication is the lack of a clear understanding for how such assays should be utilized and what the reported results ultimately indicate, or perhaps more importantly, what they do not indicate. Here, we provide a brief summary of the performance of a number of serologic assays reported in the literature, comment on what we do and do not know regarding our immune response to SARS-CoV-2, and provide a number of scenarios for which serologic testing will play a role in during our global response to this pandemic.", "qid": 7, "docid": "ile2md92", "rank": 25, "score": 9.439599990844727}, {"content": "Title: Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist Content: OBJECTIVE: As the severe acute respiratory syndrome-coronavirus-2 pandemic develops, assays to detect the virus and infection caused by it are needed for diagnosis and management. To describe to clinicians how each assay is performed, what each assay detects, and the benefits and limitations of each assay. DATA SOURCES: Published literature and internet. STUDY SELECTION: As well done, relevant and recent as possible. DATA EXTRACTION: Sources were read to extract data from them. DATA SYNTHESIS: Was synthesized by all coauthors. CONCLUSIONS: Available assays test for current or previous severe acute respiratory syndrome-coronavirus-2 infection. Nucleic acid assays such as quantitative, or real-time, polymerase chain reaction and loop-mediated isothermal amplification are ideal for acute diagnosis with polymerase chain reaction testing remaining the \u201cgold standard\u201d to diagnose acute infection by severe acute respiratory syndrome-coronavirus-2, specifically the presence of viral RNA. Assays that detect serum antibodies can theoretically diagnose both acute and remote infection but require time for the patient to develop immunity and may detect nonspecific antibodies. Antibody assays that quantitatively measure neutralizing antibodies are needed to test efficacy of convalescent plasma therapy but are more specialized.", "qid": 7, "docid": "uxeaaski", "rank": 26, "score": 9.410300254821777}, {"content": "Title: Comparison of serologic assays for measurement of antibody response to coronavirus in cats. Content: Serologic virus neutralization tests, indirect immunofluorescence tests, and ELISA, using tissue culture-adapted feline infectious peritonitis virus (FIPV) or feline enteric coronavirus (FECV) were compared for their ability to distinguish specific virus exposure in cats. Sera of specific-pathogen-free cats inoculated with virulent or modified FIPV or FECV were used to compare the sensitivity and specificity of the homologous assays to a heterologous assay that measures antibody reactivity with transmissible gastroenteritis virus of swine. The geometric means of the serologic titers in FIPV and FECV assays were higher for FIPV- or FECV-infected specific-pathogen-free cats than the geometric means of the transmissible gastroenteritis virus assays for most groups. None of the assays was specific enough to discern the virus to which a cat had been exposed. However, the FIPV virus neutralization test appeared to be more sensitive for detection of an early response to FIPV infection than did the FIPV immunofluorescence test or FIPV-ELISA.", "qid": 7, "docid": "8g5s381b", "rank": 27, "score": 9.396400451660156}, {"content": "Title: Serological microarray for detection of HSV-1, HSV-2, VZV, and CMV antibodies. Content: The seroprevalence of human herpesviruses is high and reactivations occur frequently. A microarray was designed and tested for the detection of IgG and IgM antibodies for Puumala hantavirus (PUUV) and IgG antibodies against four herpesviruses. Initially, a microarray platform was set up using an unrelated in-house antigen, PUUV recombinant nucleocapsid protein, to optimize the protocol for the detection of antibodies. Detection of the four herpesviruses was set up in a microarray using the recombinant proteins of herpes simplex virus (HSV) glycoprotein G1 and G2, varicella-zoster virus (VZV) glycoprotein E, and cytomegalovirus (CMV) pp150 phosphoprotein. The results of the PUUV panel were in good agreement with the PUUV IgG immunofluorescent assay and IgM enzyme immunoassay (EIA). Seropositive and negative clinical reference panels were tested for herpesviruses by the serological microarray, and the results were compared to those of individual EIAs used for standard diagnostic purposes. The serologic microarray for HSV, VZV and CMV antibody detection gave good specificities for IgG. However, sensitivities of the assay varied depending on the herpesvirus detected. The serological microarray showed potential for screening purposes. The microarray based analyses were easy to perform, and HSV-1, HSV-2, VZV, and CMV antibodies could be detected on the same microarray.", "qid": 7, "docid": "5iwpm4c6", "rank": 28, "score": 9.373700141906738}, {"content": "Title: Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays Content: In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antibody detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.", "qid": 7, "docid": "wf5cozst", "rank": 29, "score": 9.365400314331055}, {"content": "Title: Detection of feline coronavirus infection in captive cheetahs (Acinonyx jubatus) by polymerase chain reaction. Content: Feline coronavirus genetic elements were detected by polymerase chain reaction from blood, fecal samples, and effusive fluid collected from 33 cheetahs in the U.S.A. Feline coronavirus-specific serum antibodies were also measured by indirect immunofluorescence. Ten cheetahs were positive for viral shedding by polymerase chain reaction, whereas 13 were seropositive by immunofluorescence. Results of serology did not consistently correlate with shedding of virus, and the capture antigen used for detection of feline coronavirus-specific antibodies had a significant impact on results. Testing of samples from one population over a 1-yr period indicated chronic infection in some animals. These relatively healthy carrier animals were a source of virus for contact animals. Screening programs in cheetah populations for feline coronavirus infection may be most reliable if a combination of serologic analysis and viral detection by polymerase chain reaction is used.", "qid": 7, "docid": "j083hy74", "rank": 30, "score": 9.34589958190918}, {"content": "Title: Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review. Content: Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "qid": 7, "docid": "82iy2prw", "rank": 31, "score": 9.343799591064453}, {"content": "Title: Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review Content: Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "qid": 7, "docid": "84yjdlab", "rank": 32, "score": 9.343798637390137}, {"content": "Title: Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description Content: BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti\u2013MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti\u2013MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.", "qid": 7, "docid": "xf2ukinp", "rank": 33, "score": 9.34379768371582}, {"content": "Title: Serological Diagnosis of Feline Coronavirus Infection by Immunochromatographic Test Content: The immunochromatographic assay (ICA) is a simple antibody\u2013antigen detection method, the results of which can be rapidly obtained at a low cost. We designed an ICA to detect anti-feline coronavirus (FCoV) antibodies. A colloidal gold-labeled recombinant FCoV nucleocapsid protein (rNP) is used as a conjugate. The Protein A and affinity-purified cat anti-FCoV IgG are blotted on the test line and the control line, respectively, of the nitrocellulose membrane. The specific detection of anti-FCoV antibodies was possible in all heparin-anticoagulated plasma, serum, whole blood, and ascitic fluid samples from anti-FCoV antibody positive cats, and nonspecific reaction was not noted in samples from anti-FCoV antibody negative cats.", "qid": 7, "docid": "wfy5kz63", "rank": 34, "score": 9.309700012207031}, {"content": "Title: Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays Content: Abstract In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antiboy detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.", "qid": 7, "docid": "m9yv4qkm", "rank": 35, "score": 9.299400329589844}, {"content": "Title: Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients. Content: Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.", "qid": 7, "docid": "8e8h7bo3", "rank": 36, "score": 9.286199569702148}, {"content": "Title: Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020 Content: BackgroundThe ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making.AimOur objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies.MethodsWe developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT90) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls.ResultsIgG and IgM RBD ELISA, MN and PRNT90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test.ConclusionUsing IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT90, is a valid approach for large-scale sero-epidemiology studies.", "qid": 7, "docid": "ypj3lcpv", "rank": 37, "score": 9.283599853515625}, {"content": "Title: Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020 Content: BACKGROUND: The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making. AIM: Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies. METHODS: We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT(90)) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls. RESULTS: IgG and IgM RBD ELISA, MN and PRNT(90) were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT(90) tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test. CONCLUSION: Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT(90), is a valid approach for large-scale sero-epidemiology studies.", "qid": 7, "docid": "8m4tc16n", "rank": 38, "score": 9.275799751281738}, {"content": "Title: SARS-CoV-2 specific antibody responses in COVID-19 patients Content: A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.", "qid": 7, "docid": "9595vm0k", "rank": 39, "score": 9.270700454711914}, {"content": "Title: A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients Content: In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay.", "qid": 7, "docid": "9uj8s19h", "rank": 40, "score": 9.26729965209961}, {"content": "Title: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset Content: Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.", "qid": 7, "docid": "ndpuezpo", "rank": 41, "score": 9.258299827575684}, {"content": "Title: Characterization of novel monoclonal antibodies against the MERS-coronavirus spike protein and their application in species-independent antibody detection by competitive ELISA Content: Abstract Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold standard assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, respectively. The cELISA and neutralization test results correlated well (Pearson\u2019s correlation coefficients=0.71\u20130.76, depending on the cELISA serum dilution). This cELISA may be useful for MERS epidemiological investigations on MERS-CoV infection.", "qid": 7, "docid": "xwipcngf", "rank": 42, "score": 9.253999710083008}, {"content": "Title: Evaluation of indirect immunofluorescence antibody test and enzyme-linked immunosorbent assay for the diagnosis of infection by Leishmania infantum in clinically normal and sick cats Content: Abstract Cats that live in areas where canine and human leishmaniosis due to Leishmania infantum is endemic may become infected and may develop anti-Leishmania antibodies. In this study 50 clinically normal and 50 cats with cutaneous and/or systemic signs that lived in an endemic area and had been previously examined for infection by L. infantum using PCR in four different tissues were serologically tested for the presence of anti-Leishmania IgG (IFAT and ELISA) and IgM (IFAT). The aim was to compare the results of IFAT, ELISA and PCR and to investigate the possible associations between seropositivity to Leishmania spp and signalment, living conditions, season of sampling, health status of the cats, and seropositivity to other infectious agents. Low concentrations of anti-Leishmania IgG were detected by IFAT in 10% of the cats and by ELISA in 1%, whereas anti-Leishmania IgM were detected by IFAT in 1%. There was disagreement between the results of IFAT and ELISA for anti-Leishmania IgG (P = 0.039) and between all serological tests and PCR (P < 0.001). The diagnostic sensitivity of all serological tests, using PCR as the gold standard, was very low, but ELISA and IFAT for anti-Leishmania IgM had 100% specificity. The diagnostic sensitivity of all serological tests could not be improved by changing the cut-off values. Seropositivity for Leishmania spp was not associated with signalment, living conditions, season of sampling and health status of the cats or with seropositivity to feline leukemia virus, feline immunodeficiency virus, feline coronavirus, Toxoplasma gondii and Bartonella henselae. In conclusion, because of their low sensitivity and very high specificity two of the evaluated serological tests (ELISA for anti-Leishmania IgG and IFAT for anti-Leishmania IgM) may be useless as population screening tests but valuable for diagnosing feline infection by L. infantum.", "qid": 7, "docid": "5jtzt8um", "rank": 43, "score": 9.244400024414062}, {"content": "Title: Development of a Western blot assay for detection of antibodies against coronavirus causing severe acute respiratory syndrome. Content: To identify a major antigenic determinant for use in the development of a rapid serological diagnostic test for severe acute respiratory syndrome (SARS) coronavirus infection and to study the immune response during SARS coronavirus infection in humans, we cloned the full length and six truncated fragments of the nucleocapsid gene, expressed them, and purified them as glutathione S-transferase-tagged recombinant proteins. The reactivities of the recombinant proteins to a panel of antibodies containing 33 SARS coronavirus-positive sera and 66 negative sera and to antibodies against other animal coronaviruses were screened. A truncated 195-amino-acid fragment from the C terminus of the nucleocapsid protein (N195) was identified that had a strong ability to detect antibodies against SARS coronavirus. No cross-reaction was found between the N195 protein and antibodies against chicken, pig, and canine coronaviruses. The N195 protein was used to develop a Western blot assay to detect antibodies against SARS coronavirus in 274 clinically blinded samples. The specificity and sensitivity of this test were 98.3 and 90.9%, respectively. The correlation between our Western blotting assay and an immunofluorescence assay (IFA) was also analyzed. The results of our Western blot assay and IFA for the detection of SARS coronavirus-positive sera were the same. Thus, the N195 protein was identified as a suitable protein to be used as an antigen in Western blot and other possible assays for the detection of SARS coronavirus infection.", "qid": 7, "docid": "6se4faio", "rank": 44, "score": 9.244199752807617}, {"content": "Title: Evaluation of serological assays available in a biosafety level 2 laboratory and their application for survey of Middle East respiratory syndrome coronavirus among livestock in Ethiopia Content: A serological survey of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted among dromedary camels and herbivorous animals sharing the same pasturage in Ethiopia. The pseudotyped vesicular stomatitis virus coated with the spike protein of MERS-CoV was used in virus neutralization (VN) tests performed in a biosafety level (BSL)-2 laboratory. The results were similar to those obtained from the VN test using live MERS-CoV and were more sensitive than the ELISA performed using synthetic MERS S1 fragment as the antigen as well as the competitive ELISA performed using a monoclonal antibody against MERS-CoV. According to the comprehensive results of the four types of serodiagnosis methods, positive antibodies were detected only in dromedary camels and the remaining herbivorous animals were not infected with the virus. Moreover, using the present procedure, serological tests for MERS-CoV can be conducted even in BSL 2 laboratory.", "qid": 7, "docid": "vijh6x1l", "rank": 45, "score": 9.231300354003906}, {"content": "Title: Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Content: BACKGROUND Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.", "qid": 7, "docid": "hnbxfbeo", "rank": 46, "score": 9.219099998474121}, {"content": "Title: Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset Content: BACKGROUND: Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD: Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS: The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20\u00e2\u0080 days post exposure (d.p.e) or 9, 10 and 12\u00e2\u0080 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6\u00e2\u0080 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7\u00e2\u0080 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2\u00e2\u0080 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS: A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.", "qid": 7, "docid": "j5ag12zr", "rank": 47, "score": 9.219099044799805}, {"content": "Title: The relationship between the feline coronavirus antibody titre and the age, breed, gender and health status of Australian cats. Content: OBJECTIVES To investigate the relationship between Feline Coronavirus (FCoV) antibody titres and age, breed, gender and health status of Australian cats DESIGN Retrospective study PROCEDURE Results from two serological tests that measure FCoV antibody levels, the Coronase test and the 7B Feline Infectious Peritonitis (FIP) test, were recorded over a 2-year period, with patient signalment, history, presenting complaint and the reason for ordering the test (as available). Results from each antibody test were related to four explanatory variables (breed, age, gender and health status at the time of blood collection) using univariate ordinal logistic regression analyses, Mann Whitney U tests, one-sample sign tests or Kruskal-Wallis analyses, as appropriate. RESULTS Results from 637 Coronase and 191 7B FIP antibody tests were recorded. There were significant differences in median Coronase antibody titres between breeds of cats (P < 0.0005). Specifically, the median Coronase antibody titres of Siamese, Persians, Domestic Shorthairs and Bengal cats (100) were significantly lower than that of British Shorthairs, Cornish Rex and Burmese cats (400, P < 0.0005). There was no statistical relationship between the Coronase or 7B FIP antibody titres and age, gender or overall health status, even when considering only those cats in which clinical signs suggestive of FIP were present. CONCLUSION This study reinforces the complexity of interpreting serological tests for FCoV in both healthy cats and patients with signs compatible with FIR Unique to this study is the detection of a significant relationship between breed and median FCoV antibody titre. This supports the theory that breed related differences exist in response to FCoV infection. The distribution of median Coronase antibody titres by breed was very similar to the pattern of breed predisposition to FIP recently reported in Sydney.", "qid": 7, "docid": "eceg95dq", "rank": 48, "score": 9.213299751281738}, {"content": "Title: Comparison of serologic techniques for the detection of antibodies against feline coronaviruses. Content: The seroprevalence of feline coronavirus (FCoV) antibodies was studied in cats in southern Italy. One hundred twenty sera collected from cats belonging to catteries or community shelters and to households were tested for FCoV type I and II antibodies. The virus neutralization (VN) was performed and compared with indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). Ninety-six sera tested positive for FCoV antibodies by VN and ELISA. Interestingly, ELISA revealed 2 more positive sera than did the VN test and 3 more positive sera than did the IFAT. All results were confirmed by Western blotting. ELISA proved to be more sensitive and detected a seroprevalence of about 82%. Considering the cross-reactivity of FCoV type I and type II, ELISA was able to detect antibodies against both serotypes, allowing the use of the assay as a reference test for sera screening. The high prevalence of antibodies observed indicates that FCoVs are common in southern Italian cat populations.", "qid": 7, "docid": "xrjuma7x", "rank": 49, "score": 9.198699951171875}, {"content": "Title: Detection of feline coronavirus in captive Felidae in the USA. Content: Feline coronavirus (FCoV) is an important pathogen of domestic and nondomestic Felidae. Investigation into the prevalence of FCoV in exotic Felidae has relied primarily on serology. The usefulness of genetic detection of FCoV using reverse transcription and nested polymerase chain reaction (RT/nPCR) for viral screening was investigated. Seventy-five biologic samples, primarily feces, from captive felids from 11 institutions were tested using PCR. Serum samples collected from all but 12 of these animals were tested for antibodies to type I and type II FCoV by indirect immunofluorescence. Twenty-four animals were positive using RT/nPCR for virus. Twenty-nine animals were seropositive to type I and/or type II FCoV. From serologic data, infection with a virus antigenically related to FCoV type I occurred most commonly. Serology did not correlate with virus shedding because 13 animals were seronegative to FCoV type I and II but positive using RT/nPCR for virus. Conversely, 20 animals were seropositive but negative using RT/nPCR for FCoV. Some of the populations in which virus was detected had experienced health problems, including feline infectious peritonitis (FIP), necrotizing colitis, and mild enteritis. In addition to its role in FIP, this virus may play a role in gastrointestinal diseases of infected animals. This study demonstrates that FCoV is a significant infectious agent of captive felids because over half of the animals tested were positive by viral genetic detection, serology, or both. Dependence upon one method for detection of infection is unreliable.", "qid": 7, "docid": "xr7f1dip", "rank": 50, "score": 9.175000190734863}, {"content": "Title: Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France Content: Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using three assays: a LuLISA targeting the N protein (99% specificity), a rapid immunodiagnostic test (99.4% specificity), and a S- Flow assay (>99.5% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay. Results: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV- 2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The LuLISA N assay detected antibodies in 129 (80.6%) of the samples, with better performance for samples collected after 28 days (45/48 = 93.8%); the rapid immunodiagnostic test in 153 (95.6%); and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (none of the other tests detected antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P=0.02). Conclusion: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff after 13 days from the COVID-19 symptom onset. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.", "qid": 7, "docid": "lxkddu7u", "rank": 51, "score": 9.15429973602295}, {"content": "Title: Virological and serological studies of porcine respiratory coronavirus infection on a Japanese farm. Content: We detected transmissible gastroenteritis virus (TGEV) antibodies in pig farms in Tochigi prefecture, although the farms had no past record of TGEV vaccination or TGE. Among the farms, Farm A showed a high antibody incidence. We could not confirm if either TGEV or porcine respiratory coronavirus (PRCV) induced the antibodies, since conventional tests failed to discriminate PRCV from TGEV. Therefore, we conducted virological and serological examinations of this farm for 4 years to establish the etiology - TGEV or PRCV. Although no TGEV was detected, PRCVs were isolated from the nasal samples of pigs. Using a commercial ELISA kit, it was found that the antibodies detected in pigs of all the raising stages and sows were raised against PRCV but not TGEV. The phylogenetic analysis of the nucleotide sequences of the isolates showed that they were closely related to each other, and formed a separate cluster apart from the U.S.A. and European strains. In Cesarean-derived, colostrums-deprived piglets inoculated with a PRCV isolate, no clinical signs were seen, and the viruses were mainly isolated from the nasal samples. Moreover, viral genes were detected from the nasal sample of the contact pig. The result suggested that PRCV infection was located in the nasal cavity of pigs, and horizontal transmission easily occurs. From these results, PRCVs with different origins from the exotic PRCVs might be prevalent in pig farms in Japan.", "qid": 7, "docid": "scoyi0r3", "rank": 52, "score": 9.143799781799316}, {"content": "Title: Analysis of adjunctive serological detection to nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis Content: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. METHODS: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. RESULTS: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. CONCLUSION: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets.", "qid": 7, "docid": "t55hw2rc", "rank": 53, "score": 9.128999710083008}, {"content": "Title: A serological comparison of bovine coronavirus strains Content: Two bovine coronavirus (BCV) strains from diarrheic calf faeces were adapted to grow in HRT 18 cells and compared in immunofluorescence (IF), haemagglutination inhibition (HAI) and neutralisation (NT) tests with three other strains of BCV and a human coronavirus (HCV) strain obtained from other laboratories. Polyclonal antisera against these 6 viruses were raised in rabbits. No significant differences between viruses were detected by IF. In the HAI test the HCV strain was distinguishable from the 5 BCV strains and serological variation between the BCV strains was shown. HCV could be distinguished by NT test, but all BCV isolates were similar. Two monoclonal antibodies prepared against one of the BCV strains distinguished HCV in all three assays, and detected varying relationships between BCV strains.", "qid": 7, "docid": "7d5q0g0s", "rank": 54, "score": 9.109000205993652}, {"content": "Title: COVID\u201019 Clinical Diagnostics and Testing Technology Content: Given the global nature of the COVID\u201019 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS\u2010CoV\u20102 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID\u201019 diagnostics on the horizon. Antibody response against SARS\u2010CoV\u20102 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.", "qid": 7, "docid": "5mf1r24m", "rank": 55, "score": 9.107099533081055}, {"content": "Title: COVID-19 Clinical Diagnostics and Testing Technology Content: Given the global nature of the COVID-19 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS-CoV-2 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID-19 diagnostics on the horizon. Antibody response against SARS-CoV-2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.", "qid": 7, "docid": "afcd4wc9", "rank": 56, "score": 9.107098579406738}, {"content": "Title: Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness. Content: Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.", "qid": 7, "docid": "gzf2b2y0", "rank": 57, "score": 9.09850025177002}, {"content": "Title: Serological studies of transmissible gastroenteritis in Great Britain, using a competitive ELISA. Content: A competitive ELISA which differentiates between transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) was used to detect non-neutralising antibodies to the peplomer protein of TGEV in porcine sera. The test was shown to be TGEV specific, having a relative specificity of 100 per cent, and to have a relative sensitivity of 94.9 per cent when compared with the virus neutralisation test. The prevalence of TGEV in Great Britain is low; only 0.6 per cent of sows sampled in 1990 were seropositive to TGEV. Seroconversion to the virus neutralisation test occurred in a closed herd in 1984, with no apparent spread, but later testing by the ELISA did not detect any blocking antibodies. The possibility of the existence of a less contagious strain of PRCV is discussed. All British isolates of TGEV tested by the indirect fluorescent antibody test were recognised by the monoclonal antibody 1D.B12, the indicator antibody in the ELISA.", "qid": 7, "docid": "2n2toniv", "rank": 58, "score": 9.092499732971191}, {"content": "Title: Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients Content: OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell\u00ae POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.", "qid": 7, "docid": "czxm7so2", "rank": 59, "score": 9.061699867248535}, {"content": "Title: Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients. Content: OBJECTIVES SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell\u00ae POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.", "qid": 7, "docid": "pvo61ay8", "rank": 60, "score": 9.061698913574219}, {"content": "Title: Serological survey on canine coronavirus antibodies in giant pandas by virus neutralization test Content: In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda\u2019s sera was established by using two-fold dilutions of serum and 100 TCID(50) of the virus. The 62 sera samples of giant pandas, which were gathered from zoos and reserve region of Sichuan Province, China were detected. The neutralization antibody titer of 1:4 was recognized as the positive criterion, 8 sera samples were detected to be positive, and the positive rate was 12.9%. The titers of neutralizing antibody ranged from 1:8 to 1:32. It was the first comprehensive investigation on neutralization antibodies against CCV in giant panda population in China. The results of study showed that the infection of CCV in giant panda population was universal, which has posed a threat to the health of giant panda. Therefore, it is incumbent on us to study safe and effective vaccines to protect giant panda against CCV infection.", "qid": 7, "docid": "613j97y9", "rank": 61, "score": 9.020899772644043}, {"content": "Title: Detection of feline coronavirus infection in southern African nondomestic felids. Content: Feline coronavirus (FCoV) infects members of the Felidae family with results ranging from seroconversion with no disease to fatal feline infectious peritonitis (FIP). Infection of non-domestic felids with FCoV is of concern, particularly in endangered populations such as cheetahs (Acinonyx jubatus). In this investigation, we tested 342 animals in the Republic of South Africa and Namibia, including 140 animals from wild populations, for evidence of FCoV infection by serology and/or reverse transcription/nested polymerase chain reaction (RT/nPCR) on feces from 1999 through 2001. Past or current infection was evaluated. Of these, 195 animals had evidence of infection and included 41 animals from wild populations. Serology (indirect immunofluorescence) did not always correlate with viral RNA detection, as seronegative animals were occasionally virus-positive, while many seropositive animals were not shedding virus. Serology indicated the infecting virus was most closely related to type I FCoV. Antibody levels in the majority of animals were low, even in those actively infected. Ten of 48 animals tested at more than one time point by RT/nPCR were shedding virus at multiple time points possibly indicating persistent infection. Infection in free-ranging animals was also notable, as over a quarter of the free-ranging animals tested had evidence of current or previous FCoV infection. Testing by serology and RT/nPCR is recommended for screening for FCoV infection.", "qid": 7, "docid": "e2kfxi82", "rank": 62, "score": 9.0201997756958}, {"content": "Title: Diagnostic performance of COVID-19 serology assays Content: INTRODUCTION: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19. MATERIALS AND METHODS: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently. RESULTS: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed. CONCLUSIONS: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.", "qid": 7, "docid": "b7a2w4v9", "rank": 63, "score": 8.995699882507324}, {"content": "Title: Diagnostic performance of COVID-19 serology assays. Content: INTRODUCTION The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19. MATERIALS AND METHODS A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently. RESULTS From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed. CONCLUSIONS There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.", "qid": 7, "docid": "ij4ibrrx", "rank": 64, "score": 8.995698928833008}, {"content": "Title: Disease-specific B cell epitopes for serum antibodies from patients with severe acute respiratory syndrome (SARS) and serologic detection of SARS antibodies by epitope-based peptide antigens Content: Severe acute respiratory syndrome (SARS) has emerged as a highly contagious, sometimes fatal disease. To find disease-specific B cell epitopes, phage-displayed random peptide libraries were panned on serum immunoglobulin (Ig) G antibodies from patients with SARS. Forty-nine immunopositive phage clones that bound specifically to serum from patients with SARS were selected. These phageborne peptides had 4 consensus motifs, of which 2 corresponded to amino acid sequences reported for SARS-associated coronavirus (SARSCoV). Synthetic peptide binding and competitive-inhibition assays further confirmed that patients with SARS generated antibodies against SARS-CoV. Immunopositive phage clones and epitope-based peptide antigens demonstrated clinical diagnostic potential by reacting with serum from patients with SARS. Antibody-response kinetics were evaluated in 4 patients with SARS, and production of IgM, IgG, and IgA were documented as part of the immune response. In conclusion, B cell epitopes of SARS corresponded to novel coronavirus. Our epitope-based serologic test may be useful in laboratory detection of the virus and in further study of the pathogenesis of SARS.", "qid": 7, "docid": "nqt9lhcc", "rank": 65, "score": 8.952099800109863}, {"content": "Title: Canine coronavirus in Australian dogs Content: Objective To estimate the frequency of serum antibodies (IgG and IgM) to canine coronavirus (CCV) in the Australian dog population and evaluate the role of CCV as a causative agent of gastroenteritis. Design A serological survey of antibodies to CCV among different dog populations. Procedure The development and characterisation of an indirect ELISA for the detection of antibodies (IgG and IgM) to CCV was undertaken. Sera collected from both diarrhoeal and non\u2010diarrhoeal dogs from various populations throughout Australia were tested for these antibodies to CCV. Results Serum samples (1396) collected from 1984 to 1998 were tested for the presence of IgG antibodies to CCV. Samples were divided into two categories on the basis of the number of dogs housed together. The groups were either an open population containing dogs housed as groups of three or less, or kennel populations. Sera from 15.8% of the open population and 40.8% of kennelled dogs were positive for CCV antibodies. The prevalence of antibodies varied from zero to 76% in kennelled dogs. About 23% of 128 dogs positive for IgG antibodies to CCV were also positive for IgM antibodies to CCV, indicating recent CCV infection. Of those dogs that were presented with clinical signs of gastroenteritis such as diarrhoea and vomiting(n = 29), 85% were positive in the IgM ELISA and 85.7% in the IgG ELISA for antibodies to CCV. In comparison, for those dogs presented without any history of gastroenteritis only 15% were positive for IgM and 30% positive for IgG. Conclusion Serological evidence indicates that infection with CCV in dogs is widespread throughout the Australian mainland. The prevalence of antibodies varies greatly among different populations, with an average of 40.8% positive in kennelled populations and 15.8% in the open population.", "qid": 7, "docid": "0qw0t78s", "rank": 66, "score": 8.939399719238281}, {"content": "Title: Comparison of the antibody response to transmissible gastroenteritis virus and porcine respiratory coronavirus, using monoclonal antibodies to antigenic sites A and X of the S glycoprotein. Content: Pigs were inoculated with various strains of transmissible gastroenteritis virus (TGEV) or with porcine respiratory coronavirus (PRCV), and antigenic site-specific antibody responses were compared. A blocking-ELISA was used to study to what extent antibodies in convalescent sera interfered with the binding of monoclonal antibodies (MAB) 57.16 or 57.110 to the attenuated TGEV/Purdue virus. Monoclonal antibody 57.16 is directed against the A site on the peplomer, neutralizes virus, and recognizes TGEV and PRCV. Monoclonal antibody 57.110 is directed against the X site on the peplomer, but does not neutralize virus, and recognizes only TGEV. Antibodies directed against TGEV and PRCV could be detected in a blocking ELISA, using MAB 57.16 as a conjugate. Antibodies directed against both viruses were detectable as early as 1 week after inoculation. Antibody titers correlated well with those in a virus-neutralization test. Antibodies against TGEV could be detected in a blocking ELISA, using MAB 57.110 as a conjugate. Such antibodies were not induced by a PRCV infection. In the blocking ELISA, using MAB 57.110 as a conjugate, antibodies were detectable as early as 2 weeks after inoculation. There was a significant difference between antibody titers reached after infection with various TGEV strains, however. This difference is ascribed to a variation of the antigenic site defined by MAB 57.110 in TGEV strains. Conditions for a differential test for TGE serodiagnosis, and for serologic discrimination between TGEV- and PRCV-infected pigs, are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)", "qid": 7, "docid": "gp7jrluz", "rank": 67, "score": 8.934700012207031}, {"content": "Title: An enzyme-linked immunosorbent assay using canine coronavirus-infected CRFK cells as antigen for detection of anti-coronavirus antibody in cat Content: Abstract From the reasons that canine coronavirus (CCV) grows more efficiently than feline coronavirus in a cell culture and they are mutually related in their antigenicities, an enzyme-linked immunosorbent assay (ELISA) using CCV-infected feline kidney (CRFK) cells as substrate antigens was developed for detection of anti-coronavirus antibodies in cats. It was indispensable for generating coronavirus-specific ELISA antibody activities that the sample was applied to the mock-infected, normal CRFK cells in parallel with the CCV-infected cells and then the optical density values given by the mock-infected cell antigen were subtracted from those given by the virus-infected cell antigen. On the basis of ELISA antibody titers obtained in sera from the cats experimentally infected with CCV and from the spontaneous feline infectious peritonitis (FIP) cases, the ELISA described in the present study was found to be applicable as a simple and easy serologic test which was able to detect anti-coronavirus antibodies as efficiently as the indirect immunofluorescence assay with homologous FIP virus.", "qid": 7, "docid": "uyqqalyv", "rank": 68, "score": 8.932299613952637}, {"content": "Title: Development and validation of an enzyme-linked immunosorbent assay for human metapneumovirus serology based on a recombinant viral protein. Content: The human metapneumovirus (hMPV) is a newly reported respiratory virus belonging to the Paramyxoviridae family that has been associated with bronchiolitis and pneumonia in young children. We developed a simple enzyme-linked immunosorbent assay (ELISA) for hMPV serological testing using the nucleoprotein (N) from group A or B (N-A or N-B) as the antigen, and we evaluated it in both children and adults. The N proteins were first used in a Western immunoblot assay to identify hMPV-negative sera, which were then used to determine the cutoff value of the ELISA test. Subsequent evaluation of the ELISA-N test revealed that the mean reciprocal antibody titer of 20 randomly selected seropositive children was 143, compared to 69 for 20 seropositive adults. In a prospective evaluation of 71 adults with acute exacerbations of chronic obstructive pulmonary disease, 58 (81.6%) had prior hMPV antibodies and 3 (4.2%) had evidence of recent hMPV infection. In testing paired sera from adults (n = 4) with recent hMPV group A infection confirmed by reverse transcriptase PCR (RT-PCR), ELISAs using the N-A or N-B proteins were able to detect hMPV seroconversion. Moreover, testing of paired sera from three adults with a recent infection by the human respiratory syncytial virus confirmed by RT-PCR and serology did not reveal any increase in hMPV antibodies over time. The ELISA-N is a simple, objective, and specific serological test useful for detecting anti-hMPV antibodies following group A or B viral infections, which should permit a better understanding of the epidemiology of this virus.", "qid": 7, "docid": "gt4glete", "rank": 69, "score": 8.916099548339844}, {"content": "Title: Middle East Respiratory Syndrome Coronavirus Antibodies in Bactrian and Hybrid Camels from Dubai Content: So far, dromedary camels are the only known animal reservoir for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). Previous published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. However, a recent study revealed that direct inoculation of Bactrian camels intranasally with MERS-CoV can lead to infection with abundant virus shedding and seroconversion. In this study, we examined the presence of MERS-CoV antibodies in Bactrian and hybrid camels in Dubai, the United Arab Emirates (where dromedaries are also present), and Bactrian camels in Xinjiang, China (where dromedaries are absent). For the 29 serum samples from Bactrian camels in Dubai tested by the MERS-CoV spike (S) protein-based enzyme-linked immunosorbent assay (S-ELISA) and neutralization antibody test, 14 (48%) and 12 (41%), respectively, were positive for MERS-CoV antibodies. All the 12 serum samples that were positive with the neutralization antibody test were also positive for the S-ELISA. For the 11 sera from hybrid camels in Dubai tested with the S-ELISA and neutralization antibody test, 6 (55%) and 9 (82%), respectively, were positive for MERS-CoV antibodies. All the 6 serum samples that were positive for the S-ELISA were also positive with the neutralization antibody test. There was a strong correlation between the antibody levels detected by S-ELISA and neutralizing antibody titers, with a Spearman coefficient of 0.6262 (P < 0.0001; 95% confidence interval, 0.5062 to 0.7225). All 92 Bactrian camel serum samples from Xinjiang were negative for MERS-CoV antibodies tested using both S-ELISA and the neutralization antibody test. Bactrian and hybrid camels are potential sources of MERS-CoV infection. IMPORTANCE Since its first appearance in 2012, Middle East respiratory syndrome (MERS) has affected >25 countries, with >2,400 cases and an extremely high fatality rate of >30%. The total number of mortalities due to MERS is already greater than that due to severe acute respiratory syndrome. MERS coronavirus (MERS-CoV) has been confirmed to be the etiological agent. So far, dromedaries are the only known animal reservoir for MERS-CoV. Previously published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. In this study, we observed that 41% of the Bactrian camel sera and 55% of the hybrid camel sera from Dubai (where dromedaries are also present), but none of the sera from Bactrian camels in Xinjiang (where dromedaries are absent), were positive for MERS-CoV antibodies. Based on these results, we conclude that in addition to dromedaries, Bactrian and hybrid camels are also potential sources of MERS-CoV infection.", "qid": 7, "docid": "i26lgvbz", "rank": 70, "score": 8.912199974060059}, {"content": "Title: Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan Content: Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase\u2013polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus\u2013based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection.", "qid": 7, "docid": "zo9uzk52", "rank": 71, "score": 8.907600402832031}, {"content": "Title: Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2 Content: OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.", "qid": 7, "docid": "gplcop2k", "rank": 72, "score": 8.906200408935547}, {"content": "Title: The indirect fluorescent antibody technique as a method for detecting antibodies in aborted fetuses. Content: In this investigation the indirect fluorescent antibody technique was used to titrate antibodies in bovine sera to parainfluenza 3, infectious bovine rhinotracheitis virus and bovine viral diarrhea virus. These results were compared to those determined on the same samples by hemagglutination inhibition for parainfluenza 3 virus and serum neutralization for bovine virus diarrhea and infectious bovine rhinotracheitis virus. The results of the serological methods agreed closely. The indirect fluorescent antibody technique is a rapid and sensitive method for detecting antibodies and the procedure lends itself to use in diagnostic laboratories. In addition to the above viruses the presence or absence of antibodies to bovine coronavirus and bovine adenovirus 3 were determined by the indirect fluorescent antibody technique in thoracic fluids from 100 aborted fetuses and 50 nonaborted fetuses. Results on these samples were not compared to hemagglutination inhibition or serum neutralization as the condition of fluid samples from aborted fetuses renders interpretation of such tests unreliable. Antibodies to one or more viruses were detected in 30 of the 100 aborted fetuses and in seven of the 50 nonaborted fetuses. Antibodies to more than one agent were detected in eleven of the 100 aborted and in one of the 50 nonaborted fetuses. Reasons for this occurrence and application of the test in determination of causes of abortion are discussed.", "qid": 7, "docid": "cc7htcc8", "rank": 73, "score": 8.88379955291748}, {"content": "Title: Diagnostic Techniques: Serological and Molecular Approaches\u2606 Content: Abstract Virus laboratory diagnostics has an increasingly important role in modern patient care. Virological methods are needed to investigate the etiology of acute viral infection or the reactivation of a latent infection, as well as to follow virus load in antiviral treatments. Serological assays are also used for screening of blood products for the risk of certain chronic infections, evaluation of the immune status, and need for prophylactic treatments in connection with organ transplantations. For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient's specimens or investigation of specific antibody response in serum specimens. Amplification techniques, most commonly polymerase chain reaction (PCR) is currently the workhorse of nucleic acid testing for the detection and quantitation of virus genomes. Virus isolation is used to demonstrate infectious virus in a patient's specimens, whereas virus antigens are investigated by antigen detection assays. Serological diagnosis is based on either the demonstration of the presence of virus-specific IgM antibodies or a significant increase in the levels and/or avidity of specific IgG antibodies. Immunoassays are the most commonly used serological assays. Point-of-care tests (POC tests), for antigens, antibodies, and also nucleic acids are also becoming more and more common in diagnostic use. In order to reach the best diagnostic efficiency for each patient it is important to select the most suitable method using the right sample collected at the right time.", "qid": 7, "docid": "2u16otbf", "rank": 74, "score": 8.876700401306152}, {"content": "Title: The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.", "qid": 7, "docid": "4cqjqwk9", "rank": 75, "score": 8.875}, {"content": "Title: Coronavirus infections in horses in Saudi Arabia and Oman Content: Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT\u2010PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT\u2010PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross\u2010reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections.", "qid": 7, "docid": "qoukiqr7", "rank": 76, "score": 8.8725004196167}, {"content": "Title: Combination of Serological Total Antibody and RT-PCR Test for Detection of SARS-CoV-2 Infections Content: The purpose of this study was to investigate the feasibility of serological total antibody tests combined with RT-PCR for detection of SARS-CoV-2. We conducted a retrospective study in which 375 patients were enrolled during the outbreak of SARS-CoV-2 from 25th January to 16th March 2020. Patients were divided into a COVID-19 group (n = 141) and a control group (n = 234). Serum samples and throat swabs were collected from 375 patients for total antibody testing against SARS-CoV-2 and RT-PCR analysis, respectively. The results indicated that diagnostic sensitivity and specificity were 95.7% and 98.7%, 92.2% and 100% by total antibody tests and RT-PCR, respectively. The sensitivity and specificity of total antibody tests combined with RT-PCR were 98.6% and 98.7%. The sensitivity of the combined method was significantly higher than RT-PCR (X(2) = 5.16, P < 0.05), and similar to that of total antibody tests (X(2) = 1.15, P > 0.05). This study supported the advantage of the combined method for detection of SARS-CoV-2 with a high degree of sensitivity and specificity, as a useful tool for accurate diagnosis and timely treatment of suspected patients, epidemiological investigation, as well as monitoring ongoing outbreaks of infections with SARS-CoV-2.", "qid": 7, "docid": "m2otfdjw", "rank": 77, "score": 8.870699882507324}, {"content": "Title: Combination of serological total antibody and RT-PCR test for detection of SARS-COV-2 infections Content: The purpose of this study was to investigate the feasibility of serological total antibody tests combined with RT-PCR for detection of SARS-COV-2. We conducted a retrospective study in which 375 patients were enrolled during the outbreak of SARS-COV-2 from 25th January to 16th March 2020. Patients were divided into a COVID-19 group (n = 141) and a control group (n = 234). Serum samples and throat swabs were collected from 375 patients for total antibody testing against SARS-COV-2 and RT-PCR analysis, respectively. The results indicated that diagnostic sensitivity and specificity were 95.7 % and 98.7 %, 92.2 % and 100 % by total antibody tests and RT-PCR, respectively. The sensitivity and specificity of total antibody tests combined with RT-PCR were 98.6 % and 98.7 %. The sensitivity of the combined method was significantly higher than RT-PCR (X2 = 5.16, P < 0.05), and similar to that of total antibody tests (X2 = 1.15, P> 0.05). This study supported the advantage of the combined method for detection of SARS-COV-2 with a high degree of sensitivity and specificity, as a useful tool for accurate diagnosis and timely treatment of suspected patients, epidemiological investigation, as well as monitoring ongoing outbreaks of infections with SARS-COV-2.", "qid": 7, "docid": "xy6pj7bt", "rank": 78, "score": 8.870698928833008}, {"content": "Title: Validation and Performance Comparison of Three SARS-CoV-2 Antibody Assays Content: Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly being used during the current pandemic of Coronavirus Disease 2019 (COVID-19). The clinical and epidemiologic utilities of antibody-based SARS-CoV-2 testing are under debate. Characterizing these assays helps to understand the disease and provides scientific basis for deciding how to best use these assays. The study assessed one chemiluminescent assay (Abbott COVID-2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo Total Antibody Test). Validation included 113 blood samples from 71 PCR-confirmed COVID-19 patients and 1182 samples from negative controls with potential interferences/cross-reactions, including 1063 pre-pandemic samples. IgM antibodies against SARS-CoV-2 were detected as early as post-symptom onset days 3-4. IgG antibodies were first detected post-onset days 5-6 by SQ assays. The detection rates increased gradually, and SQ IgG, Abbott IgG and Wondfo Total detected antibodies from all the PCR-confirmed patients 14 days after symptom onset. Overall agreements between SQ IgM/IgG and Wondfo Total was 88.5% and between SQ IgG and Abbott IgG was 94.6% (Kappa = 0.75, 0.89). No cross-reaction with other endemic coronavirus infections were identified. Viral hepatitis and autoimmune samples were the main cross-reactions observed. However, the interferences/cross-reactions were low. The specificities were 100% for SQ IgG and Wondfo Total and 99.62% for Abbott IgG and 98.87% for SQ IgM. These findings demonstrate high sensitivity and specificity of appropriately validated antibody-based SARS-CoV-2 assays with implications for clinical use and epidemiological seroprevalence studies.", "qid": 7, "docid": "maa43hpn", "rank": 79, "score": 8.847999572753906}, {"content": "Title: Evaluation of serological cross-reactivity and cross-neutralization between the United States porcine epidemic diarrhea virus prototype and S-INDEL-variant strains Content: BACKGROUND: At least two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the United States (U.S. PEDV prototype and S-INDEL-variant strains). The current serological assays offered at veterinary diagnostic laboratories for detection of PEDV-specific antibody are based on the U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting weaned pigs; 3) determine if the various PEDV serological assays could detect antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS: A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study. Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3) PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera against the prototype strain reacted to and neutralized both prototype and S-INDEL-variant viruses, and the positive antisera against the S-INDEL-variant strain also reacted to and neutralized both prototype and S-INDEL-variant viruses, as examined by IFA antibody assays and VN tests. Antibodies against the two PEDV strains could be detected by all three ELISAs although detection rates varied to some degree. CONCLUSIONS: These data indicate that the antibodies against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross-neutralized both strains in vitro. The current serological assays based on U.S. PEDV prototype strain can detect antibodies against both U.S. PEDV strains.", "qid": 7, "docid": "svd6ls12", "rank": 80, "score": 8.840900421142578}, {"content": "Title: Seroprevalence of Antibodies to SARS-CoV-2 in Healthcare Workers in Non-epidemic Region: A Report from Iwate Prefecture in Japan Content: Background: As of June 8, 2020, Iwate is the only one of 47 prefectures in Japan with no confirmed coronavirus disease 2019 (COVID-19) cases. Serological survey for COVID-19 antibodies is crucial in area with low prevalence as well as epidemic area when addressing health and social issues caused by COVID-19. Rapid, accurate and easy-to-use antibody tests as well laboratory-based antibody tests are necessary for confirming immunity in a given community. Methods:Serum samples from healthcare workers (n = 1,000, mean 40 {+/-} 11 years) of Iwate Prefectural Central Hospital, Iwate, Japan were tested for the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Two laboratory-based quantitative tests (Abbott Architect SARS-CoV-2 IgG and Roche Elecsys Anti-SARS-CoV-2 assays) and one point-of-care (POC) qualitative test (Alfa Instant-view plus COVID-19 Test) were performed simultaneously. Sensitivity and specificity were 100%, 99.6% in Abbott assay; 100%, 99.8% in Roche assay; 97.8%, 94.6% in Alfa POC test, respectively. Results:The laboratory-based quantitative tests showed positive in 4 of 1,000 samples (0.4%) (95% CI: 0.01 to 0.79): 4/1,000 (0.4%) (95% CI: 0.01 to 0.79) in Abbott; 0/1,000 (0%) in Roche. Positive samples were not detected for both Abbott and Roche assays. The POC qualitative test showed positive in 33 of 1,000 samples (3.3%) (95% CI: 2.19 to 4.41), showing higher rates than those of the laboratory-based quantitative tests. There were no samples with simultaneous positive reaction for two quantitative tests and a POC test. Conclusions: Infected COVID-2 cases were not confirmed by a retrospective serological study in healthcare workers of our hospital. The POC qualitative tests with lower specificity have the potential for higher false positive reactions than the laboratory-based quantitative tests in areas with very low prevalence of COVID-19.", "qid": 7, "docid": "bj8wn9dh", "rank": 81, "score": 8.837499618530273}, {"content": "Title: Prevalence of canine coronavirus (CCoV) in dog in Japan: detection of CCoV RNA and retrospective serological analysis Content: We collected rectal swabs from dogs in Japan during 2011 to 2014, and canine coronavirus (CCoV) nucleocapsid gene was detected by RT-PCR. The relationship between CCoV infection and the manifestation of diarrhea symptoms was investigated, and a correlation was noted (df=1, \u03c7(2)=8.90, P<0.005). The types of CCoV detected in samples from CCoV-infected dogs were CCoV-I in 88.9% and CCoV-II in 7.4%, respectively. We retrospectively investigated the seroprevalence of CCoV-I in dogs in Japan during 1998 to 2006. The sera were tested with a neutralizing antibody test. In the absence of CCoV-I laboratory strain, we used feline coronavirus (FCoV)-I that shares high sequence homology in the S protein with CCoV-I. 77.7% of the sera were positive for neutralizing anti-FCoV-I antibodies.", "qid": 7, "docid": "2kg967bh", "rank": 82, "score": 8.827799797058105}, {"content": "Title: Development of an enzyme-linked immunosorbent assay-based test with a cocktail of nucleocapsid and spike proteins for detection of severe acute respiratory syndrome-associated coronavirus-specific antibody. Content: A new enzyme-linked immunosorbent assay (ELISA)-based immunoglobulin G (IgG)-plus-IgM antibody detection test for severe acute respiratory syndrome (SARS) has been developed by using a cocktail of four recombinant polypeptides as the antigen. These recombinant fragments were designed as parts of two different structural proteins from SARS-associated coronavirus (SARS-CoV). One recombinant polypeptide, S251-683, was designed as part of the spike glycoprotein, and the other three polypeptides comprised almost the whole nucleocapsid protein, avoiding the last 25 C-terminal amino acids. Immunization with a cocktail of these four polypeptides yielded a specific polyclonal antibody that is able to recognize SARS-CoV-infected cells by an immunofluorescence assay. This polypeptide cocktail was also used to set up an ELISA-based IgG-plus-IgM antibody detection test, which showed 99% specificity and 90% sensitivity upon evaluation using sera from 100 healthy negative controls and 20 SARS patients. Separate immunoreactivity assays with each recombinant polypeptide demonstrated that a combination of N and S protein fragments was more suitable than the individual peptides for developing a serological assay for SARS-CoV.", "qid": 7, "docid": "pt3k01vx", "rank": 83, "score": 8.822500228881836}, {"content": "Title: Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019 Content: OBJECTIVE: To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. RESULTS: Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. CONCLUSIONS: Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.", "qid": 7, "docid": "5ig5upot", "rank": 84, "score": 8.81029987335205}, {"content": "Title: Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019 Content: Abstract Objective To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). Methods This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. Results Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. Conclusions Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.", "qid": 7, "docid": "ir3k848j", "rank": 85, "score": 8.810298919677734}, {"content": "Title: Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection Content: BACKGROUND: Thousands of medical staff had been infected with SARS-CoV-2 virus with hundreds of deaths reported. Such loss could be prevented if there is a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using CHO cell expressed full length SARS-CoV-2 S1 protein as capturing antigen, a COVID-19/SARS-CoV-2 S1 serology ELISA kit was developed and validated with negative samples collected prior to the outbreaks or during the outbreak, and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day one after the onset of COVID-19 disease. The average antibody levels increased during the hospitalization and after been discharged for two weeks. SARS-CoV-2 antibodies were detected in 28 out of 276 asymptomatic medical staff and one out of five nucleic acid test-negative \u201cClose contacts\u201d of COVID-19 patient. CONCLUSION: With the assays developed here, we can screen medical staff, in-coming patients, passengers and people who are in close contact with the confirmed patients to identify the \u201cinnocent viral spreaders\u201d, protect the medical staff and stop the further spreading of the virus.", "qid": 7, "docid": "juooj31c", "rank": 86, "score": 8.80459976196289}, {"content": "Title: Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection Content: BACKGROUND: Thousands of medical staff had been infected with SARS-CoV-2 virus with hundreds of deaths reported. Such loss could be prevented if there is a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using CHO cell expressed full length SARS-CoV-2 S1 protein as capturing antigen, a COVID-19/SARS-CoV-2 S1 serology ELISA kit was developed and validated with negative samples collected prior to the outbreaks or during the outbreak, and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day one after the onset of COVID-19 disease. The average antibody levels increased during the hospitalization and after been discharged for two weeks. SARS-CoV-2 antibodies were detected in 28 out of 276 asymptomatic medical staff and one out of five nucleic acid test-negative \"Close contacts\" of COVID-19 patient. CONCLUSION: With the assays developed here, we can screen medical staff, in-coming patients, passengers and people who are in close contact with the confirmed patients to identify the \"innocent viral spreaders\", protect the medical staff and stop the further spreading of the virus.", "qid": 7, "docid": "o2vl31aq", "rank": 87, "score": 8.804598808288574}, {"content": "Title: Feline coronavirus serotypes 1 and 2: seroprevalence and association with disease in Switzerland. Content: To determine the prevalence of antibodies to feline coronavirus (FCoV) serotypes 1 and 2 in Switzerland and their association with different disease manifestations, a serological study based on immunofluorescence tests was conducted with Swiss field cats using transmissible gastroenteritis virus (TGEV), FCoV type 1 and FCoV type 2 as antigens. A total of 639 serum samples collected in the context of different studies from naturally infected cats were tested. The current study revealed that, with an apparent prevalence of 83%, FCoV serotype 1 is the most prevalent serotype in Switzerland. FCoV type 1 viruses induced higher antibody titers than FCoV type 2, and were more frequently associated with clinical signs and/or feline infectious peritonitis. The antibody development in seven cats experimentally infected with FCoV type 1 revealed that, with progressing duration of infection, antibodies to FCoV type 1 significantly increased over those to FCoV type 2. There was a significant relationship between antibody titers against TGEV, FCoV 1, and FCoV 2 and TGEV antigen detected the highest proportion of seropositive cats. We conclude that a vaccine against FCoV should be based on FCoV type 1-related antigens and that for serodiagnosis of FCoV infection TGEV should be used to attain the highest diagnostic efficiency. When serology is used in addition to clinical signs, hematology, and clinical chemistry results as an aid to diagnose clinical FIP, TGEV shows a diagnostic efficiency equal to that of a FCoV antigen.", "qid": 7, "docid": "rx81w320", "rank": 88, "score": 8.798500061035156}, {"content": "Title: Serology in the Digital Age: Using Long Synthetic Peptides Created from Nucleic Acid Sequences as Antigens in Microarrays Content: Background: Antibodies to microbes, or to autoantigens, are important markers of disease. Antibody detection (serology) can reveal both past and recent infections. There is a great need for development of rational ways of detecting and quantifying antibodies, both for humans and animals. Traditionally, serology using synthetic antigens covers linear epitopes using up to 30 amino acid peptides. Methods: We here report that peptides of 100 amino acids or longer (\u201cmegapeptides\u201d), designed and synthesized for optimal serological performance, can successfully be used as detection antigens in a suspension multiplex immunoassay (SMIA). Megapeptides can quickly be created just from pathogen sequences. A combination of rational sequencing and bioinformatic routines for definition of diagnostically-relevant antigens can, thus, rapidly yield efficient serological diagnostic tools for an emerging infectious pathogen. Results: We designed megapeptides using bioinformatics and viral genome sequences. These long peptides were tested as antigens for the presence of antibodies in human serum to the filo-, herpes-, and polyoma virus families in a multiplex microarray system. All of these virus families contain recently discovered or emerging infectious viruses. Conclusion: Long synthetic peptides can be useful as serological diagnostic antigens, serving as biomarkers, in suspension microarrays.", "qid": 7, "docid": "i6jhquze", "rank": 89, "score": 8.79580020904541}, {"content": "Title: Preliminary Results of Seroprevalence of SARS-CoV-2 at Community Clinics in Tokyo Content: Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n =202) was performed in two community clinics in Tokyo, Japan. The overall positive rate of SRAS-CoV-2 IgG antibody was 5.9% (95% confidence interval[CI]: 3.1-10.1). Higher rate was observed for healthcare workers (n =55, 9.1 [3.0-20.0]). The limitation on antibody tests includes low sensitivity and potent cross-reactivity with the previous coronavirus. Robust healthcare policy to efficiently monitor COVID-19 spread is warranted in Tokyo.", "qid": 7, "docid": "vchnxw27", "rank": 90, "score": 8.785300254821777}, {"content": "Title: Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 Content: BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. METHODS: A total of 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n=535) collected during the hospitalization were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2. The dynamics of antibodies with the disease progress was analyzed. RESULTS: Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1%, 82.7% and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might due to the lack of blood samples at the later stage of illness. The median seroconversion time for Ab, IgM and then IgG were day-11, day-12 and day-14, separately. The presence of antibodies was <40% among patients within 1-week since onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM) and 79.8% (IgG) since day-15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day-7 to 45.5% (25/55) during day 15-39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (p<0.001), even in early phase of 1-week since onset (p=0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p=0.006). CONCLUSIONS: The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.", "qid": 7, "docid": "2yjuf053", "rank": 91, "score": 8.779199600219727}, {"content": "Title: Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera Content: Emergence of the novel pathogenic coronavirus Sars-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus and assessment of seroprevalence levels in the population, both of which form the basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in improvement of sensitivity and specificity compared to an approved ELISA-based diagnostic test. Combining both methods resulted in maximum specificity in a negative control cohort, while maintaining high sensitivity. The procedure described here is compatible with high-throughput microscopy approaches and may be applied for serological analysis of other virus infections.", "qid": 7, "docid": "scd3f8vk", "rank": 92, "score": 8.760100364685059}, {"content": "Title: Sensitive detection of SARS-CoV-2-specific-antibodies in dried blood spot samples Content: Abstract Importance: Population-wide serological testing is an essential component in understanding the COVID-19 pandemic. The logistical challenges of undertaking widespread serological testing could be eased through use of a reliable dried blood spot (DBS) sampling method. Objective: To validate the use of dried blood spot sampling for the detection of SARS-CoV-2-specific antibodies. Design, setting and participants: Eighty-seven matched DBS and serum samples were obtained from eighty individuals, including thirty-one who were previously PCR-positive for SARS-CoV-2. DBS eluates and sera were used in an ELISA to detect antibodies to the viral spike protein. Results: Specific anti-SARS-Cov-2 spike glycoprotein antibodies were detectable in both serum and DBS eluate and there was a significant correlation between the antibody levels detected in matched samples (r = 0.96, p<0.0001). Using serum as the gold standard in the assay, matched DBS samples achieved a Cohens kappa coefficient of 0.975 (near-perfect agreement), a sensitivity of 98.1% and specificity of 100%, for detecting anti-spike glycoprotein antibodies. Conclusions and relevance: Eluates from DBS samples are a reliable and reproducible source of antibodies to be used for the detection of SARS-CoV-2-specific antibodies. The use of DBS sampling could complement the use of venepuncture in the immunosurveillance of COVID-19 in both low and high income settings.", "qid": 7, "docid": "imxby1b1", "rank": 93, "score": 8.758899688720703}, {"content": "Title: Antigenic Relationship between Human Coronavirus Strain DC 43 and Hemagglutinating Encephalomyelitis Virus Strain 67N of Swine: Antibody Responses in Human and Animal Sera Content: Hemagglutinating encephalomyelitis virus of swine (HEV) was adapted to growth in suckling mouse brain. Electron micrographs of HEV-infected suckling mouse brain, prepared by negative staining and thin-section techniques, exhibited typical morphological characteristics shared with other members of the Coronaviridae. The adaptation of HEV to suckling mouse brain facilitated serologic testing by the use of common host reagents and compatible animal systems. With hemagglutination inhibition, complement-fixation, and neutralization tests, an antigenic relationship was demonstrated between human coronavirus OC 43 and HEV in specific immune and hyperimmune animal sera. Children and adults with seroconversion to OC 43 antigen had diagnostic rises in titer of antibody to HEV antigens. Individuals with seroconversion to human coronaviruses 229E and B814 demonstrated antibody to HEV but not diagnostic rises in titer. Swine with titers of antibody to HEV had lower or no detectable titers of antibody to coronavirus OC 43. Although the prevalence and geometric mean titer of antibody to DC 43 were higher than the titer of antibody to HEV in every group of normal humans tested, significant differences in antibody response to coronavirus DC 43 and HEV were seen between populations that did or did not have possible contact with swine. The evidence suggested that antibody to HEV in humans probably represented a heterologous response to infection with coronavirus DC 43. However, a heterotypic response to unknown or uncharacterized strains of coronavirus cannot be excluded.", "qid": 7, "docid": "tc402gn4", "rank": 94, "score": 8.757399559020996}, {"content": "Title: An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment Content: The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.", "qid": 7, "docid": "cv2dg9tg", "rank": 95, "score": 8.749099731445312}, {"content": "Title: Serologic Detection of Latent SARS-CoV-2 Infections in Hemodialysis Centers: A Multi-center, Retrospective Study in Wuhan, China. Content: RATIONALE & OBJECTIVE Maintenance hemodialysis (MHD) patients are a population highly vulnerable to infection with SARS-CoV-2. The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese MHD patients. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS From Dec 1, 2019 to Mar 31, 2020, 1027 MHD patients in five large hemodialysis centers in Wuhan, China were enrolled. Patients were screened by blood tests, chest computed tomography, NAT and antibody tests for SARS-CoV-2. EXPOSURE NAT and antibody tests for SARS-CoV-2. OUTCOMES Morbidity, clinical features, laboratory and radiologic findings. ANALYTICAL Approach Differences between groups were examined by Student's t-test or Mann-Whitney U test, comparing those not infected to those infected and comparing those with infection detected by NAT to with positive serology tests and negative NAT. RESULTS Of the 1027 MHD patients, 99 cases have been identified as SARS-CoV-2 infection, equivalent to a prevalence of 9.6%. In the 99 cases, 52 (53%) patients were diagnosed with SARS-CoV-2 infection by positive NAT; 47 (48%) patients were identified by positive IgG or IgM antibodies against SARS-CoV-2 with negative NAT. The spectrum of antibody profiles in these 47 patients showed IgM antibodies in 5 (11%), IgG antibodies in 35 (75%), and both positive IgM and IgG antibodies in 7 (15%). 51% of the infected patients were asymptomatic during the epidemic. Patients with hypertensive kidney disease were more often identified with infection by SARS-CoV-2 infection and they tended to be more symptomatic than other patient groups. LIMITATIONS Possibility of false positives and false negatives for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS Half of the SARS-CoV-2 infections in MHD patients were subclinical and unidentified by universal chest CT and selective NAT. Serologic testing may help to evaluate the overall prevalence and understand the diversity of clinical course among MHD patients infected with SARS-CoV-2.", "qid": 7, "docid": "e6zj71b6", "rank": 96, "score": 8.743399620056152}, {"content": "Title: Serologic Detection of Latent SARS-CoV-2 Infections in Hemodialysis Centers: A Multi-center, Retrospective Study in Wuhan, China Content: RATIONALE & OBJECTIVE: Maintenance hemodialysis (MHD) patients are a population highly vulnerable to infection with SARS-CoV-2. The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese MHD patients. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From Dec 1, 2019 to Mar 31, 2020, 1027 MHD patients in five large hemodialysis centers in Wuhan, China were enrolled. Patients were screened by blood tests, chest computed tomography, NAT and antibody tests for SARS-CoV-2. EXPOSURE: NAT and antibody tests for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, laboratory and radiologic findings. ANALYTICAL: Approach Differences between groups were examined by Student's t-test or Mann-Whitney U test, comparing those not infected to those infected and comparing those with infection detected by NAT to with positive serology tests and negative NAT. RESULTS: Of the 1027 MHD patients, 99 cases have been identified as SARS-CoV-2 infection, equivalent to a prevalence of 9.6%. In the 99 cases, 52 (53%) patients were diagnosed with SARS-CoV-2 infection by positive NAT; 47 (48%) patients were identified by positive IgG or IgM antibodies against SARS-CoV-2 with negative NAT. The spectrum of antibody profiles in these 47 patients showed IgM antibodies in 5 (11%), IgG antibodies in 35 (75%), and both positive IgM and IgG antibodies in 7 (15%). 51% of the infected patients were asymptomatic during the epidemic. Patients with hypertensive kidney disease were more often identified with infection by SARS-CoV-2 infection and they tended to be more symptomatic than other patient groups. LIMITATIONS: Possibility of false positives and false negatives for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half of the SARS-CoV-2 infections in MHD patients were subclinical and unidentified by universal chest CT and selective NAT. Serologic testing may help to evaluate the overall prevalence and understand the diversity of clinical course among MHD patients infected with SARS-CoV-2.", "qid": 7, "docid": "ks04zh6f", "rank": 97, "score": 8.743398666381836}, {"content": "Title: Evaluation of a computer-assisted, kinetics-based enzyme-linked immunosorbent assay for detection of coronavirus antibodies in cats. Content: A computer-assisted, kinetics-based enzyme-linked immunosorbent assay was adapted for the detection of coronavirus antibodies in feline serum. An alkaline antigen diluent (carbonate-bicarbonate buffer, pH 9.6) used in initial experiments produced diffuse, nonspecific color reactions in both viral and control antigen cuvettes which were correlated, paradoxically, with coronavirus antibody levels in test sera. These interfering reactions were minimized by use of lower-pH antigen diluents such as water and phosphate-buffered saline. Background kinetics-based enzyme-linked immunosorbent assay reactivity directed against a noncoronaviral component of antigen tissue culture fluids could then detected in numerous sera, particularly in samples with lower titers. Much of this reactivity was shown to be associated with bovine gamma globulins in cell culture fluid. It was not serum lot or species specific, since a variety of bovine serum lots as well as individual lots of serum from other mammalian and avian species reacted. Reactivity was markedly reduced when cells for antigen preparation were grown in gamma globulin-free bovine serum. Generation of corrected slope values from the kinetics-based enzyme-linked immunosorbent assay made it possible to correct for residual background reactivity in individual test sera and thus eliminate a potentially major source of false-positive reactions. Collectively, these studies indicated that the control of nonspecific reactivity in feline coronavirus serology is absolutely essential to obtain useful estimates of specific antibody responses.", "qid": 7, "docid": "ku45p8f2", "rank": 98, "score": 8.737700462341309}, {"content": "Title: Serologic survey for selected viral pathogens in free-ranging endangered European mink (Mustela lutreola) and other mustelids from south-western France. Content: To investigate the possible role of selected pathogens in the decline of endangered European mink (Mustela lutreola) populations and the potential for these pathogens to affect mink survival, a serologic survey was conducted using serum samples collected from March 1996 to March 2003 in eight departments of south-western France. In total, 481 free-ranging individuals of five mustelid species (including the European mink) were tested. Sympatric mustelids can serve as sentinels to determine the presence of antibodies to viruses in the study area that could potentially infect mink. Antibodies to Canine distemper virus (CDV) were detected in all species; 9% of 127 European mink, 20% of 210 polecats (Mustela putorius), 5% of 112 American mink (Mustela vison), 33% of 21 stone marten (Martes foina) and 5% of 20 pine marten (Martes martes). Antibody prevalence was significantly higher in stone marten and polecats, possibly because their ranges overlap more closely with that of domestic species than that of the other species tested. Antibodies to Canine adenovirus were detected in all species but the pine marten; antibody prevalence estimates ranging from 2% to 10%. Antibodies to canine parainfluenza virus were detected in 1% of European mink, 1% of American mink and 5% of tested polecats but were not detected in Martes species. Antibodies to Rabies virus (RV) were detected in three animals, possibly because of interspecies transmission of bat lyssaviruses as the sampling area is considered to be free of RV, or to a lack of test specificity, as antibody titers were low. The high antibody prevalence to potentially lethal CDV suggests that this pathogen could have significant effects on the free-ranging populations and has implications for the conservation efforts for the endangered European mink.", "qid": 7, "docid": "scnlgep2", "rank": 99, "score": 8.724800109863281}, {"content": "Title: Diagnostic Techniques: Serological and Molecular Approaches Content: Virus laboratory diagnostics has an increasingly important role in modern patient care. Virological methods are needed to investigate the etiology of acute viral infection or the reactivation of a latent infection, as well as to follow virus load in antiviral treatments. Serological assays are also used for screening of blood products for the risk of certain chronic infections, evaluation of the immune status, and need for prophylatic treatments in connection with organ transplantations. For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient's specimens or investigation of specific antibody response in serum specimes. Virus isolation is used to demonstrate infectious virus in a patient's specimens, whereas nucleic acid amplification techniques, like polymerase chain reaction (PCR), are widely used to detect virus nucleic acids. Virus antigens are investigated by antigen detection assays. Serological diagnosis is based on either the demonstration of the presence of virus-specific IgM antibodies or a significant increase in the levels of specific IgG antibodies. Immunoassays are the most commonly used serological assays. Point-of-care tests (POC tests), both for antigens and antibodies, are also becoming more and more common in diagnostic use. In order to reach the best diagnostic efficiency for each patient it is important to select the most suitable method using the right sample collected at the right time.", "qid": 7, "docid": "jg0br2ro", "rank": 100, "score": 8.707300186157227}]}
{"query": "how has lack of testing availability led to underreporting of true incidence of Covid-19?", "hits": [{"content": "Title: Accounting for underreporting in mathematical modelling of transmission and control of COVID-19 in Iran Content: BACKGROUND: Iran has been the hardest hit country by the outbreak of SARS-CoV-2 in the Middle East with 74,877 confirmed cases and 4,683 deaths as of 15 April 2020. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant under-reporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. We use a mathematical epidemic model utilizing official confirmed data and estimates of underreporting to understand how transmission in Iran has been changing between February and April 2020. METHODS: We developed a compartmental transmission model to estimate the effective reproduction number and its fluctuations since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method also accounts for the underreporting due to low case ascertainment by estimating the percentage of symptomatic cases using delay adjusted case fatality ratio based on the distribution of the delay from hospitalization to death. FINDINGS: Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60-1.87) on 1 March 2020 to 0.69 (95% CI 0.68-0.70) on 15 April 2020, due to various non-pharmaceutical interventions including school closures, a ban on public gatherings including sports and religious events, and full or partial closure of non-essential businesses. Based on these estimates and given that a near complete containment is no longer feasible, it is likely that the outbreak may continue until the end of the 2020 if the current level of physical distancing and interventions continue and no effective vaccination or therapeutic are developed and made widely available. INTERPRETATION: The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19 within the studied time period. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead the public health decisions, policy makers, and general public especially in the earlier stages of the outbreak. FUNDING: Nil.", "qid": 8, "docid": "ll2pnl81", "rank": 1, "score": 11.450900077819824}, {"content": "Title: New blood tests for antibodies could show true scale of coronavirus pandemic Content: How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease\u2014perhaps so mild they dismissed it as a cold or allergies\u2014immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests\u2014for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune\u2014is still lacking or at least not public Scientists hope that will soon change as more tests become available", "qid": 8, "docid": "ecxji8x8", "rank": 2, "score": 10.448200225830078}, {"content": "Title: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters Content: Abstract Background With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. Methods We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. Results The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. Conclusions Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "qid": 8, "docid": "ckecol7i", "rank": 3, "score": 10.376399993896484}, {"content": "Title: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters Content: BACKGROUND: With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. METHODS: We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. RESULTS: The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. CONCLUSIONS: Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "qid": 8, "docid": "hnbatlj0", "rank": 4, "score": 10.376399040222168}, {"content": "Title: Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate Content: Since the novel coronavirus disease (COVID-19) emerged in December 2019 in China, it has rapidly spread around the world, leading to one of the most significant pandemic events of recent history. Deriving reliable estimates of the COVID-19 epidemic growth rate is quite important to guide the timing and intensity of intervention strategies. Indeed, many studies have quantified the epidemic growth rate using time-series of reported cases during the early phase of the outbreak to estimate the basic reproduction number, R0. Using daily time series of COVID-19 incidence, we illustrate how epidemic curves of reported cases may not always reflect the true epidemic growth rate due to changes in testing rates, which could be influenced by limited diagnostic testing capacity during the early epidemic phase.", "qid": 8, "docid": "79gozr1p", "rank": 5, "score": 10.142999649047852}, {"content": "Title: Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate Content: Abstract Since the novel coronavirus disease (COVID-19) emerged in December 2019 in China, it has rapidly propagated to around the world, leading to one of the most significant pandemic events of recent history. Deriving reliable estimates of the COVID-19 epidemic growth rate is quite important to guide the timing and intensity of intervention strategies. Indeed, many studies have quantified the epidemic growth rate using time-series of reported cases during the early phase of the outbreak to estimate the basic reproduction number, R 0. Using daily time series of COVID-19 incidence, we illustrate how epidemic curves of reported cases may not always reflect the true epidemic growth rate due to changes in testing rates, which could be influenced by limited diagnostic testing capacity during the early epidemic phase.", "qid": 8, "docid": "dz1lfwzp", "rank": 6, "score": 10.142998695373535}, {"content": "Title: Bounding the Predictive Values of COVID-19 Antibody Tests Content: COVID-19 antibody tests have imperfect accuracy. There has been lack of clarity on the meaning of reported rates of false positives and false negatives. For risk assessment and clinical decision making, the rates of interest are the positive and negative predictive values of a test. Positive predictive value (PPV) is the chance that a person who tests positive has been infected. Negative predictive value (NPV) is the chance that someone who tests negative has not been infected. The medical literature regularly reports different statistics, sensitivity and specificity. Sensitivity is the chance that an infected person receives a positive test result. Specificity is the chance that a non-infected person receives a negative result. Knowledge of sensitivity and specificity permits one to predict the test result given a person's true infection status. These predictions are not directly relevant to risk assessment or clinical decisions, where one knows a test result and wants to predict whether a person has been infected. Given estimates of sensitivity and specificity, PPV and NPV can be derived if one knows the prevalence of the disease, the rate of illness in the population. There is considerable uncertainty about the prevalence of COVID-19. This paper addresses the problem of inference on the PPV and NPV of COVID-19 antibody tests given estimates of sensitivity and specificity and credible bounds on prevalence. I explain the methodological problem, show how to estimate bounds on PPV and NPV, and apply the findings to some tests authorized by the FDA.", "qid": 8, "docid": "yvtk83x6", "rank": 7, "score": 10.124899864196777}, {"content": "Title: Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? Content: Abstract: The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how SARS-CoV-2 may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. Methods Without prior knowledge of how this virus would affect our transplant center\u2019s delivery of care to KTRs who are SARS-CoV-2 positive or Patients Under Investigation (PUIs), and in the setting of limited testing availability, we initiated a Quality Assurance and Improvement Project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. Results Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department, or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without history of BKV (80% and 28%, respectively; p= 0.002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (p=0.06).", "qid": 8, "docid": "upwsdgso", "rank": 8, "score": 9.993599891662598}, {"content": "Title: Hyperlocal Postcode Based Crowdsourced Surveillance Systems in the COVID-19 Pandemic Response Content: The SARS-CoV-2 pandemic has rapidly saturated healthcare resources across the globe and has led to a restricted screening process, hindering efforts at comprehensive case detection. This has not only facilitated community spread but has also resulted in an underestimation of the true incidence of disease, a statistic which is useful for policy making aimed at controlling the current pandemic and in preparing for future outbreaks. In this perspective, we present a crowdsourced platform developed by us for the true estimation of all SARS-CoV-2 infections in the community, through active self-reporting and layering other authentic datasets. The granularity of data captured by this system could prove to be useful in assisting governments to identify SARS-CoV-2 hotspots in the community facilitating lifting of restrictions in a controlled fashion.", "qid": 8, "docid": "0cu6gi44", "rank": 9, "score": 9.805000305175781}, {"content": "Title: Severe acute respiratory syndrome coronavirus 2, original antigenic sin, and antibody-dependent enhancement: m\u00e9nage \u00e0 trois. Content: BACKGROUND Shortly after its emergence in December 2019, the coronavirus disease 2019 (COVID-19) was declared as a pandemic by the World Health Organization. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the seventh member of the Coronaviridae family of viruses that causes disease in humans. THE PROBLEM Despite the established role of molecular diagnostics, COVID-19 serodiagnosis remains a poorly discovered and enigmatic area. Although there are numerous commercial serological products available globally, there is a severe paucity of high-quality peer-reviewed literature on their true performance characteristics. That being said, publications including in-house developed serological tests started to shed light on the kinetics of the humoral response. SUMMARY In spite of intense focus of assessing the performance characteristics of the commercially-available kits, the main issue remains rather invisible, that is, lack of solid science behind COVID-19 serology its clinical usefulness thereof. This short review summarizes the key points as to why COVID-19 is not jest ready to fly. PURPOSE OF REVIEW Despite having been mentioned as a testing option, COVID-19 serology has significant shortcomings that needs discussing. This short review is meant to shed light on one of those aspects.", "qid": 8, "docid": "ugx8unte", "rank": 10, "score": 9.679200172424316}, {"content": "Title: Group Testing for Sars-Cov-2 to Enable Rapid Scale-Up of Testing and Real-Time Surveillance of Incidence Content: High-throughput molecular testing for SARS-CoV-2 may be enabled by group testing in which pools of specimens are screened, and individual specimens tested only after a pool tests positive. Several labs have recently published examples of pooling strategies applied to SARS-CoV-2 specimens, but overall guidance on efficient pooling strategies is lacking. Therefore we developed a model of the efficiency and accuracy of specimen pooling algorithms based on available data on SAR-CoV-2 viral dynamics. For a fixed number of tests, we estimate that programs using group testing could screen 2 to 20 times as many specimens compared to individual testing; increase the total number of true positive infections identified; and improve the positive predictive value of results. We compare outcomes that may be expected in different testing situations and provide general recommendations for group testing implementation. A free, publicly-available web calculator is provided to help inform laboratory decisions on SARS-CoV-2 pooling algorithms.", "qid": 8, "docid": "dx6tji56", "rank": 11, "score": 9.642800331115723}, {"content": "Title: Identification of spatial variations in COVID-19 epidemiological data using K-Means clustering algorithm: a global perspective Content: Background: Discerning spatial variations of COVID-19 through quantitative analysis operating on the geographically designated datasets relating to socio-demographics and epidemiological data facilitate strategy planning in curtailing the transmission of the disease and focus on articulation of necessary interventions in an informed manner. Methods: K-means clustering was employed on the available country-specific COVID-19 epidemiological data and the influential background characteristics. Country-specific case fatality rates and the average number of people tested positive for COVID-19 per every 10,000 population in each country were derived from the WHO COVID-19 situation report 107, and were used for clustering along with the background characteristics of proportion of countrys population aged >65 years and percentage GDP spent as public health expenditure. Results: The algorithm grouped the 89 countries into cluster 1 and Cluster 2 of sizes 54 and 35, respectively. It is apparent that Americas, European countries, and Australia formed a major part of cluster 2 with high COVID-19 case fatality rate, higher proportion of countrys population tested COVID-19 positive, higher percentage of GDP spent as public health expenditure, and greater percentage of population being more than 65 years of age. Conclusion: In spite of the positive correlation between high public health expenditure (%GDP) and COVID-19 incidence, case fatality rate, the immediate task ahead of most of the low and middle income countries is to strengthen their public health systems realizing that the correlation found in this study could be spurious in light of the underreported number of cases and poor death registration.", "qid": 8, "docid": "2kiyzq4b", "rank": 12, "score": 9.593199729919434}, {"content": "Title: Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan. Content: BACKGROUND Under the unique Japanese policy to restrict reverse transcriptase-polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors. AIM Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for COVID-19. DESIGN Cross-sectional study using regression and correlation analysis. METHODS We retrieved domestic laboratory-confirmed cases, deaths, and the number of RT-PCR testing for COVID-19 from January 15 to April 6, 2020 in 47 prefectures in Japan, using publicly-available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis. RESULTS The median prefectural-level incidence and number of RT-PCR testing per 100,000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (p < 0.001) and the number of RT-PCR testing (p = 0.03); and those for RT-PCR testing were the incidence (p = 0.025), available beds (p = 0.045) and cluster infections (p = 0.034). CONCLUSION Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.", "qid": 8, "docid": "7gmacx72", "rank": 13, "score": 9.466699600219727}, {"content": "Title: Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan Content: BACKGROUND: Under the unique Japanese policy to restrict reverse transcriptase-polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors. AIM: Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for COVID-19. DESIGN: Cross-sectional study using regression and correlation analysis. METHODS: We retrieved domestic laboratory-confirmed cases, deaths, and the number of RT-PCR testing for COVID-19 from January 15 to April 6, 2020 in 47 prefectures in Japan, using publicly-available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis. RESULTS: The median prefectural-level incidence and number of RT-PCR testing per 100,000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (p < 0.001) and the number of RT-PCR testing (p = 0.03); and those for RT-PCR testing were the incidence (p = 0.025), available beds (p = 0.045) and cluster infections (p = 0.034). CONCLUSION: Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.", "qid": 8, "docid": "nwfbo4zj", "rank": 14, "score": 9.46669864654541}, {"content": "Title: Excess registered deaths in England and Wales during the COVID-19 pandemic, March 2020 to May 2020 Content: Official counts of COVID-19 deaths have been criticized for potentially including people who did not die of COVID-19 but merely died with COVID-19. I address that critique by fitting a generalized additive model to weekly counts of all deaths registered in England and Wales during the 2010s. The model produces baseline rates of death registrations expected without the COVID-19 pandemic, and comparing those baselines to recent counts of registered deaths exposes the emergence of excess deaths late in March 2020. By April's end, England and Wales registered 45,300 $\\pm$ 3200 excess deaths of adults aged 45+. Through 22 May, the last day of available all-deaths data, 56,600 $\\pm$ 4400 were registered (about 53% of which were of men). Both the ONS's corresponding count of 43,205 death certificates which mention COVID-19, and the Department of Health and Social Care's count of 33,671 deaths, are appreciably less, implying that their counting methods have underestimated, not overestimated, the pandemic's true death toll. If underreporting rates have held steady during May, about 59,000 direct and indirect COVID-19 deaths might have been registered through the end of May but not yet publicly reported in full.", "qid": 8, "docid": "713u1uw3", "rank": 15, "score": 9.442899703979492}, {"content": "Title: COVID-19: Are Africa\u2019s diagnostic challenges blunting response effectiveness? Content: Since its emergence in Wuhan, China in December 2019, novel Coronavirus disease - 2019 (COVID-19) has rapidly spread worldwide, achieving pandemic status on 11 (th) March, 2020. As of 1 (st) April 2020, COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had infected over 800,000 people and caused over 40,000 deaths in 205 countries and territories. COVID-19 has had its heaviest toll on Europe, United States and China. As of 1 (st) of April 2020, the number of confirmed COVID-19 cases in Africa was relatively low, with the highest number registered by South Africa, which had reported 1,380 confirmed cases. On the same date (also the date of this review), Africa had reported 5,999 confirmed cases, of which 3,838 (almost 65%) occurred in South Africa, Algeria, Egypt, Morocco and Tunisia, with the remaining 2,071 cases distributed unevenly across the other African countries. We speculate that while African nations are currently experiencing much lower rates of COVID-19 relative to other continents, their significantly lower testing rates may grossly underestimate incidence rates. Failure to grasp the true picture may mean crucial windows of opportunity shut unutilized, while limited resources are not deployed to maximum effect. In the absence of extensive testing data, an overestimation of spread may lead to disproportionate measures being taken, causing avoidable strain on livelihoods and economies. Here, based on the African situation, we discuss COVID-19 diagnostic challenges and how they may blunt responses.", "qid": 8, "docid": "i9ndb71n", "rank": 16, "score": 9.423399925231934}, {"content": "Title: Finding Covid-19 from Chest X-rays using Deep Learning on a Small Dataset Content: Testing for COVID-19 has been unable to keep up with the demand. Further, the false negative rate is projected to be as high as 30% and test results can take some time to obtain. X-ray machines are widely available and provide images for diagnosis quickly. This paper explores how useful chest X-ray images can be in diagnosing COVID-19 disease. We have obtained 122 chest X-rays of COVID-19 and over 4,000 chest X-rays of viral and bacterial pneumonia. A pretrained deep convolutional neural network has been tuned on 102 COVID-19 cases and 102 other pneumonia cases in a 10-fold cross validation. The results were all 102 COVID-19 cases were correctly classified and there were 8 false positives resulting in an AUC of 0.997. On a test set of 20 unseen COVID-19 cases all were correctly classified and more than 95% of 4171 other pneumonia examples were correctly classified. This study has flaws, most critically a lack of information about where in the disease process the COVID-19 cases were and the small data set size. More COVID-19 case images will enable a better answer to the question of how useful chest X-rays can be for diagnosing COVID-19 (so please send them).", "qid": 8, "docid": "7gsl7d3f", "rank": 17, "score": 9.152000427246094}, {"content": "Title: Barriers to conducting deprescribing in the elderly population amid the COVID-19 pandemic Content: Deprescribing aims to reduce polypharmacy, especially in the elderly population, in order to maintain or improve quality of life, reduce harm from medications, and limit healthcare expenditure. Coronavirus disease (COVID-19) is an infectious disease that has led to a pandemic and has changed the lives many throughout the world. The mode of transmission of this virus is from person to person through the transfer of respiratory droplets. Therefore, non-essential healthcare services involving direct patient interactions, including deprescribing, has been on hiatus to reduce spread. Barriers to deprescribing before the pandemic include patient and system related factors, such as resistance to change, patient's knowledge deficit about deprescribing, lack of alternatives for treatment of disease, uncoordinated delivery of health services, prescriber's attitudes and/or experience, limited availability of guidelines for deprescribing, and lack of evidence on preventative therapy. Some of these barriers can be mitigated by using the following interventions:patient education, prioritization of non-pharmacological therapy, incorporation of electronic health record (EHR), continuous prescriber education, and development of research studies on deprescribing. Currently, deprescribing cannot be delivered through in person interactions, so virtual care is a reasonable alternative format. The full incorporation of EHR throughout Canada can add to the success of this strategy. However, there are several challenges of conducting deprescribing virtually in the elderly population. These challenges include, but are not limited, to their inability to use technology, lack of literacy, lack of assistance from others, greater propensity for withdrawal effects, and increased risk of severe consequences, if hospitalized. Virtual care is the future of healthcare and in order to retain the benefits of deprescribing, additional initiatives should be in place to address the challenges that elderly patients may experience in accessing deprescribing virtually. These initiatives should involve teaching elderly patients how to use technology to access health services and with technical support in place to address any concerns.", "qid": 8, "docid": "hkg91ivj", "rank": 18, "score": 9.057499885559082}, {"content": "Title: Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods Content: Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country over time, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach, coupled with Monte Carlo methods, to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 countries where reliable data are available. We find a positive relationship between the testing rate per 1,000 people and the implied true detection rate of COVID-19, and a negative relationship between the proportion who test positive and the implied true detection rate. Our estimates suggest that the true number of people infected across our sample of 15 developed countries is 18.2 (5-95% CI: 11.9-39.0) times greater than the reported number of cases. In individual countries, the true number of cases exceeds the reported figure by factors that range from 1.7 (5-95% CI: 1.1-3.6) for Australia to 35.6 (5-95% CI: 23.2-76.3) for Belgium.", "qid": 8, "docid": "vq7k0gma", "rank": 19, "score": 9.051199913024902}, {"content": "Title: COVID 19 in Bangladesh: Assumption of possible infection and death Content: Abstract: It is a painful job to predict the death of people. But sometimes it is important to predict the future and concern the government. A furious future is waiting for Bangladesh. Objective: Objective of the study is to assume the number of positive case and death till 30th December, 2020 in Bangladesh. Study design: This study was designed with systematic review and data analysis. Method: The study was completed by analyzing data available on website. First COVID 19 case in Bangladesh was identified on 8th March. Analyzing the data increasing rate/common ratio of infection and death has been identified. Then this common ratio has been used in the formula of multiplication series. Data of China, Iran, Italy and the USA was also analyzed to assume how the death and case number increased. Social issues of Bangladesh were also analyzed. Considering all these the assumption was made. Result: It has been assumed that by the 43rd week (on 30th December, 2020) of first identification the total case can be 17024322 and total death can be 86265 by 30 December, 2020. As this is an assumption this can be true, partially true or false. But the base of assumption is strong enough so the possibility of being true or nearly true is higher. Policy Suggestion: Government should choose properly one between two options. Either government should declare curfew or let people lead normal life. A very weak lock down for a long time does not make any sense.", "qid": 8, "docid": "o5u8vfva", "rank": 20, "score": 9.025899887084961}, {"content": "Title: Urologic Surgery and COVID-19: How the Pandemic Is Changing the Way We Operate Content: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on all aspects of health care, including surgical procedures. For urologists, it has affected and will continue to influence how we approach the care of patients preoperatively, intraoperatively, and postoperatively. A risk-benefit assessment of each patient undergoing surgery should be performed during the COVID-19 pandemic based on the urgency of the surgery and the risk of viral illness and transmission. Patients with advanced age and comorbidities have a higher incidence of mortality. Routine preoperative testing and symptom screening is recommended to identify those with COVID-19. Adequate personal protective equipment (PPE) for the surgical team is essential to protect health care workers and ensure an adequate workforce. For COVID-19 positive or suspected patients, the use of N95 respirators is recommended if available. The anesthesia method chosen should attempt to minimize aerosolization of the virus. Negative pressure rooms are strongly preferred for intubation/extubation and other aerosolizing procedures for COVID-19 positive patients or when COVID status is unknown. Although transmission has not yet been shown during laparoscopic and robotic procedures, efforts should be made to minimize the risk of aerosolization. Ultra-low particulate air filters are recommended for use during minimally invasive procedures to decrease the risk of viral transmission. Thorough cleaning and sterilization should be performed postoperatively with adequate time allowed for the operating room air to be cycled after procedures. COVID-19 patients should be separated from noninfected patients at all levels of care, including recovery, to decrease the risk of infection. Future directions will be guided by outcomes and infection rates as social distancing guidelines are relaxed and more surgical procedures are reintroduced. Recommendations should be adapted to the local environment and will continue to evolve as more data become available, the shortage of testing and PPE is resolved, and a vaccine and therapeutics for COVID-19 are developed.", "qid": 8, "docid": "4ri37klx", "rank": 21, "score": 8.97249984741211}, {"content": "Title: A novel IDEA: The impact of serial interval on a modified-Incidence Decay and Exponential Adjustment (m-IDEA) model for projections of daily COVID-19 cases Content: The SARS-CoV-2 virus causes the disease COVID-19, and has caused high morbidity and mortality worldwide. Empirical models are useful tools to predict future trends of disease progression such as COVID-19 over the near-term. A modified Incidence Decay and Exponential Adjustment (m-IDEA) model was developed to predict the progression of infectious disease outbreaks. The modification allows for the production of precise daily estimates, which are critical during a pandemic of this scale for planning purposes. The m-IDEA model was employed using a range of serial intervals given the lack of knowledge on the true serial interval of COVID-19. Both deterministic and stochastic approaches were applied. Model fitting was accomplished through minimizing the sum-of-square differences between predicted and observed daily incidence case counts, and performance was retrospectively assessed. The performance of the m-IDEA for projection cases in the near-term was improved using shorter serial intervals (1\u20134 days) at early stages of the pandemic, and longer serial intervals at mid-to late-stages (5\u20139 days) thus far. This, coupled with epidemiological reports, suggests that the serial interval of COVID-19 might increase as the pandemic progresses, which is rather intuitive: Increasing serial intervals can be attributed to gradual increases in public health interventions such as facility closures, public caution and social distancing, thus increasing the time between transmission events. In most cases, the stochastic approach captured the majority of future reported incidence data, because it accounts for the uncertainty around the serial interval of COVID-19. As such, it is the preferred approach for using the m-IDEA during dynamic situation such as in the midst of a major pandemic.", "qid": 8, "docid": "pem3eqiz", "rank": 22, "score": 8.941399574279785}, {"content": "Title: Urologic surgery and COVID-19: How the pandemic is changing the way we operate. Content: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on all aspects of healthcare, including surgical procedures. For urologists, it has affected and will continue to influence how we approach the care of patients pre-operatively, intra-operatively, and post-operatively. A risk-benefit assessment of each patient undergoing surgery should be performed during the COVID-19 pandemic based on the urgency of the surgery and the risk of viral illness and transmission. Patients with advanced age and comorbidities have a higher incidence of mortality. Routine preoperative testing and symptom screening is recommended to identify those with COVID-19. Adequate personal protective equipment (PPE) for the surgical team is essential to protect healthcare workers and ensure an adequate workforce. For COVID-19 positive or suspected patients, the use of N95 respirators is recommended if available. The anesthesia method chosen should attempt to minimize aerosolization of the virus. Negative pressure rooms are strongly preferred for intubation/extubation and other aerosolizing procedures. Although transmission has not yet been shown during laparoscopic and robotic procedures, efforts should be made to minimize the risk of aerosolization. Ultra low particulate air filters are recommended for use during minimally invasive procedures to decrease the risk of viral transmission. Thorough cleaning and sterilization should be performed post-operatively with adequate time allowed for the operating room air to be cycled after procedures. COVID-19 patients should be separated from non-infected patients at all levels of care including recovery to decrease the risk of infection. Future directions will be guided by outcomes and infection rates as social distancing guidelines are relaxed and more surgical procedures are reintroduced. Recommendations should be adapted to the local environment and will continue to evolve as more data becomes available, the shortage of testing and PPE is resolved, and a vaccine and therapeutics for COVID-19 are developed.", "qid": 8, "docid": "b9gtfwym", "rank": 23, "score": 8.925399780273438}, {"content": "Title: Estimation of Undetected Covid-19 Infections in India Content: Background and Objectives: While the number of detected COVID-19 infections are widely available, an understanding of the extent of undetected COVID- 19 cases is urgently needed for an effective tackling of the pandemic and as a guide to lifting the lockdown. The aim of this work is to estimate and predict the true number of COVID-19 (detected and undetected) infections in India for short to medium forecast horizons. In particular, using publicly available COVID-19 infection data upto 16th April 2020, we predict the true number of infections in India during and upto the end of the formal lockdown period (21st April 2020). Methods: The high death rate observed in most COVID-19 hit countries is suspected to be a function of the undetected infections existing in the population. An estimate of the age weighted infection fatality rate (IFR) of the disease of 0.41%, specifically calculated by taking into account the age structure of Indian population, is already available in the literature. In addition, the recorded case fatality rate (CFR= 0.70%) of Kerala, the only state in India to report single digit new infections over the second week of April, is used as a second estimate of the IFR. These estimates are used to formulate a relationship between deaths recorded and the true number of infections. The estimated undetected and detected cases time series based on these two IFR estimates are then used to fit a discrete time multivariate infection model to predict the total infections at the end of the formal lockdown period. Results: In two consecutive fortnights during the lockdown, it was noted that the rise in detected infections has decreased by 2.7 times. For an IFR of 0.41%, the rise in undetected infections decreased by 3.2 times and the predicted number of total infections in India is 3.14 lakhs. While for an IFR of 0.70%, the rise in undetected cases decreased by 3.3 times and the total number of infections predicted on 21st April is 1.75 lakhs. Interpretation and Conclusions: The behaviour of the undetected cases over time effectively illustrates the effects of lockdown and increased testing. From our estimates, it is found that the lockdown has brought down the undetected to detected cases ratio, and has consequently dampened the increase in the number of total cases. However, even though the rate of rise in total infections has fallen, the lifting of the lockdown should be done keeping in mind that 1.75 to 3 lakhs undetected cases will already exist in the population on 21st April.", "qid": 8, "docid": "t4d2ibng", "rank": 24, "score": 8.873499870300293}, {"content": "Title: Number of International Arrivals Predicts Severity of the first Global Wave of the COVID-19 Pandemic Content: Background: Reported death rates from different countries during the COVID-19 pandemic vary. Lack of universal testing and death underreporting make between-country comparisons difficult. The country-level determinants of COVID-19 mortality are unknown. Objective: Derive a measure of COVID-related death rates that is comparable across countries and identify its country-level predictors. Methods: An ecological study design of publicly available data was employed. Countries reporting >25 COVID-related deaths until May 1, 2020 were included. The outcome was the mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential predictors assessed were most recently published Demographic parameters (population and population density, percentage population living in urban areas, median age, average body mass index, smoking prevalence), Economic parameters (Gross Domestic Product per capita; environmental parameters: pollution levels, mean temperature (January-April)), co-morbidities (prevalence of diabetes, hypertension and cancer), health systems parameters (WHO Health Index and hospital beds per 10,000 population and international arrivals). Multivariable linear regression was used to analyse the data. Results: Thirty-one countries were included. Of all country-level predictors included in the multivariable model, only total number of international arrivals was significantly associated with the mean death rate: Beta 0.3798 (95% Confidence Interval 0.2414, 0.5182), P <0.001. Conclusion: International travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Stopping international travel, particularly from affected areas, may be the most effective strategy to control COVID outbreak and prevent related deaths.", "qid": 8, "docid": "2v4lrlcl", "rank": 25, "score": 8.845100402832031}, {"content": "Title: High-sensitivity COVID-19 group testing by digital PCR Content: Background: Worldwide demand for SARS-CoV-2 RT-PCR testing is increasing as more countries are impacted by COVID-19 and as testing remains central to contain the spread of the disease, both in countries where the disease is emerging and in countries that are past the first wave but exposed to re-emergence. Group testing has been proposed as a solution to expand testing capabilities but sensitivity concerns have limited its impact on the management of the pandemic. Digital PCR (RT-dPCR) has been shown to be more sensitive than RT-PCR and could help in this context. Methods: We implemented RT-dPCR based COVID-19 group testing on commercially available system and assay (Naica System from Stilla Technologies) and investigated the sensitivity of the method in real life conditions of a university hospital in Paris, France, in May 2020. We tested the protocol in a direct comparison with reference RT-PCR testing on 448 samples split into groups of 3 sizes for RT-dPCR analysis: 56 groups of 8 samples, 28 groups of 16 samples and 14 groups of 32 samples. Results: Individual RT-PCR testing identified 25 positive samples. Using groups of 8, testing by RT-dPCR identified 23 groups as positive, corresponding to 26 true positive samples including 2 samples not initially detected by individual RT-PCR but confirmed positive by further RT-PCR and RT-dPCR investigation. For groups of 16, 15 groups tested positive, corresponding to 25 true positive samples identified. 100% concordance is found for groups of 32 but with limited data points.", "qid": 8, "docid": "xtx8hl14", "rank": 26, "score": 8.771100044250488}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60\u201395%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-020-00367-6) contains supplementary material, which is available to authorized users.", "qid": 8, "docid": "3p9yc6ti", "rank": 27, "score": 8.723699569702148}, {"content": "Title: Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazi Content: The current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.", "qid": 8, "docid": "zhcamsqa", "rank": 28, "score": 8.715700149536133}, {"content": "Title: Underreporting of death by COVID-19 in Brazil's second most populous state Content: The COVID-19 pandemic brings to light the reality of the Brazilian health system. The underreporting of COVID-19 deaths in the state of Minas Gerais (MG), where is concentrated the second largest population of the country, reveals government unpreparedness, as there is a low capacity of testing in the population, which prevents the real understanding of the general panorama of Sars-Cov-2 dissemination. The goals of this research are to analyze the causes of deaths in the different Brazilian government databases (ARPEN and SINAN) and to assess whether there are sub-records shown by the unexpected increase in the frequency of deaths from causes clinically similar to COVID-19. A descriptive and quantitative analysis of the number of COVID-19 deaths and similar causes was made in different databases. Ours results demonstrate that the different official sources had a discrepancy of 209.23% between these data referring to the same period. There was also a 648.61% increase in SARS deaths in 2020, when compared to the average of previous years. Finally, it was shown that there was an increase in the rate of pneumonia and respiratory insufficiency (RI) by 5.36% and 5.72%, respectively. In conclusion, there is an underreporting of COVID-19 deaths in MG due to the unexplained excess of SARS deaths, Respiratory insufficiency and pneumonia compared to previous years.", "qid": 8, "docid": "kusqyumn", "rank": 29, "score": 8.657299995422363}, {"content": "Title: COVID-19 in England: spatial patterns and regional outbreaks Content: Aims: to investigate the spatiotemporal distribution of COVID-19 cases in England; to provide spatial quantification of risk at a high resolution; to provide information for prospective antigen and serological testing. Approach: We fit a spatiotemporal Negative Binomial generalised linear model to Public Health England SARS-CoV-2 testing data at the Lower Tier Local Authority region level. We assume an order-1 autoregressive model for case progression within regions, coupling discrete spatial units via observed commuting data and time-varying measures of traffic flow. We fit the model via maximum likelihood estimation in order to calculate region-specific risk of ongoing transmission, as well as measuring regional uncertainty in incidence. Results: We detect marked heterogeneity across England in COVID-19 incidence, not only in raw estimated incidence, but in the characteristics of within-region and between-region dynamics of PHE testing data. There is evidence for a spatially diverse set of regions having a higher daily increase of cases than others, having accounted for current case numbers, population size, and human mobility. Uncertainty in model estimates is generally greater in rural regions. Conclusions: A wide range of spatial heterogeneity in COVID-19 epidemic distribution and infection rate exists in England currently. Future work should incorporate fine-scaled demographic and health covariates, with continued improvement in spatially-detailed case reporting data. The method described here may be used to measure heterogeneity in real-time as behavioural and social interventions are relaxed, serving to identify \"hotspots\" of resurgent cases occurring in diverse areas of the country, and triggering locally-intensive surveillance and interventions as needed. Caveats: There is general concern over the ability of PHE testing data to capture the true prevalence of infection within the population, though this approach is designed to provide measures of spatial prevalence based on testing that can be used to guide further future testing effort. Now-casts of epidemic characteristics are presented based on testing data alone (as opposed to \"true\" prevalence in any one area). The model used in this analysis is phenomenological for ease and speed of principled parameter inference; we choose the model which best fits the current spatial case timeseries, without attempting to enforce \"SIR\"-type epidemic dynamics.", "qid": 8, "docid": "43jy23ic", "rank": 30, "score": 8.655200004577637}, {"content": "Title: Translating COVID-19 Pandemic Surge Theory to Practice in the Emergency Department: How to Expand Structure Content: Multiple professional societies, nongovernment and government agencies have studied the science of sudden onset disaster mass casualty incidents to create and promote surge response guidelines. The COVID-19 pandemic has presented the health-care system with challenges that have limited science to guide the staff, stuff, and structure surge response.This study reviewed the available surge science literature specifically to guide an emergency department's surge structural response using a translational science approach to answer the question: How does the concept of sudden onset mass casualty incident surge capability apply to the process to expand COVID-19 pandemic surge structure response?The available surge structural science literature was reviewed to determine the application to a pandemic response. The on-line ahead of print and print COVID-19 scientific publications, as well as gray literature were studied to learn the best available COVID-19 surge structural response science. A checklist was created to guide the emergency department team's COVID-19 surge structural response.", "qid": 8, "docid": "ailig3qi", "rank": 31, "score": 8.63379955291748}, {"content": "Title: Translating COVID-19 Pandemic Surge Theory to Practice in the Emergency Department: How to Expand Structure Content: Multiple professional societies, nongovernment and government agencies have studied the science of sudden onset disaster mass casualty incidents to create and promote surge response guidelines. The COVID-19 pandemic has presented the health-care system with challenges that have limited science to guide the staff, stuff, and structure surge response. This study reviewed the available surge science literature specifically to guide an emergency department\u2019s surge structural response using a translational science approach to answer the question: How does the concept of sudden onset mass casualty incident surge capability apply to the process to expand COVID-19 pandemic surge structure response? The available surge structural science literature was reviewed to determine the application to a pandemic response. The on-line ahead of print and print COVID-19 scientific publications, as well as gray literature were studied to learn the best available COVID-19 surge structural response science. A checklist was created to guide the emergency department team\u2019s COVID-19 surge structural response.", "qid": 8, "docid": "ltk5hfc4", "rank": 32, "score": 8.633798599243164}, {"content": "Title: Host response-based screening to identify undiagnosed cases of COVID-19and expand testing capacity Content: The COVID-19 pandemic has created unprecedented challenges in diagnostic testing. At the beginning of the epidemic, a confluence of factors resulted in delayed deployment of PCR-based diagnostic tests, resulting in lack of testing of individuals with symptoms of the disease. Although these tests are now more widely available, it is estimated that a three- to ten-fold increase in testing capacity will be required to ensure adequate surveillance as communities reopen(1). In response to these challenges, we evaluated potential roles of host-response based screening in the diagnosis of COVID-19. Previous work from our group showed that the nasopharyngeal (NP) level of CXCL10, a protein produced as part of the host response to viral infection, is a sensitive predictor of respiratory virus infection across a wide spectrum of viruses(2). Here, we show that NP CXCL10 is elevated during SARS-CoV-2 infection and use a CXCL10-based screening strategy to identify four undiagnosed cases of COVID-19 in Connecticut in early March. In a second set of samples tested at the Yale New Haven Hospital, we show that NP CXCL10 had excellent performance as a rule-out test (NPV 0.99, 95% C.I. 0.985-0.997). Our results demonstrate how biomarker-based screening could be used to leverage existing PCR testing capacity to rapidly enable widespread testing for COVID-19.", "qid": 8, "docid": "6f2nzvhz", "rank": 33, "score": 8.601499557495117}, {"content": "Title: Modelling the Effect of Area-deprivation on COVID-19 Incidences: A Study of Chennai Megacity, India Content: Abstract Objectives Socioeconomic inequalities may affect COVID-19 incidence. The goal of the research was to explore the association between deprivation of socioeconomic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. Study design Ecological (or contextual) study for electoral wards (sub-cities) of Chennai megacity. Methods Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai municipal corporation, we examined the incidence of COVID-19 diseases using two count regression models namely, Poisson Regression (PR) and Negative Binomial Regression (NBR). As explanatory factors, we considered area-deprivation that represented the deprivation of socioeconomic status (SES). An index of multiple deprivations (IMD) developed to measure the area-deprivation using an advanced local statistic, Geographically Weighted Principal Component Analysis (GWPCA). Based on the availability of appropriately scaled data, five domains (i.e. poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. Results The Hot-spot analysis revealed that area-deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adj. R2: 72.2%) with the lower BIC (124.34) and AIC (112.12) for the NBR compared to PR suggests that the NBR model better explains the relationship between area-deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests, and p<0.05 was considered statistically significant. The outcome of the PR and NBR suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or in other words, the wards with high housing deprivation having 119% higher probability (RR= e0.786=2.19, 95% CI=1.98 to 2.40) compared to areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher compared to the wards with good WaSH services (RR= e0.642=1.90, 95% CI=1.79 to 2.00). Spatial risks of COVID-19 infections were predominantly concentrated in the wards with higher levels of area-deprivation which were mostly located in the north-eastern parts of Chennai megacity. Conclusions We formulated an area-based IMD, which was substantially related to COVID-19 incidences in the Chennai megacity. This study highlights that the risks of COVID-19 infections tend to be higher in more deprived areas of SES and the north-eastern part of Chennai megacity was predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area-deprivation.", "qid": 8, "docid": "k6y7f9d2", "rank": 34, "score": 8.574600219726562}, {"content": "Title: Hemogram Data as a Tool for Decision-making in COVID-19 Management: Applications to Resource Scarcity Scenarios Content: Background: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. Purpose: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. Methods: A Naive-Bayes model for machine learning is proposed for handling different scarcity scenarios, including managing symptomatic essential workforce and absence of diagnostic tests. Hemogram result data was used to predict qRT-PCR results in situations where the latter was not performed, or results are not yet available. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. Results: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity. Data assessment can be performed in an individual or simultaneous basis, according to desired outcome. Based on hemogram data and background scarcity context, resource distribution is significantly optimized when model-based patient selection is observed, compared to random choice. The model can help manage testing deficiency and other critical circumstances. Conclusions: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.", "qid": 8, "docid": "bquse0bs", "rank": 35, "score": 8.550700187683105}, {"content": "Title: Hemogram Data as a Tool for Decision-making in COVID-19 Management: Applications to Resource Scarcity Scenarios Content: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. Methods: A Naive-Bayes model for machine learning is proposed for handling different scarcity scenarios, including managing symptomatic essential workforce and absence of diagnostic tests. Hemogram result data was used to predict qRT-PCR results in situations where the latter was not performed, or results are not yet available. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity. Data assessment can be performed in an individual or simultaneous basis, according to desired outcome. Based on hemogram data and background scarcity context, resource distribution is significantly optimized when model-based patient selection is observed, compared to random choice. The model can help manage testing deficiency and other critical circumstances. Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.", "qid": 8, "docid": "v7b6z86y", "rank": 36, "score": 8.550699234008789}, {"content": "Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa Content: In 2014\u20132016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections.", "qid": 8, "docid": "zymh8c6w", "rank": 37, "score": 8.548999786376953}, {"content": "Title: Simulation-based Estimation of the Spread of COVID-19 in Iran Content: Background: The 2019 Coronavirus (COVID-19) has turned into a global pandemic with unprecedented challenges for the global community. Understanding the state of the disease and planning for future trajectories relies heavily on data on the spread and mortality. Yet official data coming from various countries are highly unreliable: symptoms similar to common cold in majority of cases and limited screening resources and delayed testing procedures may contribute to under-estimation of the burden of disease. Anecdotal and more limited data are available, but few have systematically combined those with official statistics into a coherent view of the epidemic. This study is a modeling-in-real-time of the emerging outbreak for understanding the state of the disease. Our focus is on the case of the spread of disease in Iran, as one of the epicenters of the disease in the first months of 2020. Method: We develop a simple dynamic model of the epidemic to provide a more reliable picture of the state of the disease based on existing data. Building on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework we incorporate two behavioral and logistical considerations. First we capture the endogenous changes in contact rate (average contact per person) as more death are reported. As a result the reproduction number changes endogenously in the model. Second we differentiate reported and true cases by including simple formulations for how only a fraction of cases might be diagnosed, and how that fraction changes in response to epidemic's progression. In estimating the model we use both the official data as well as the discovered infected travelers and unofficial medical community estimates and triangulate these sources to build a more complete picture. Calibration is completed by forming a likelihood function for observing the actual time series data conditional on model parameters, and conducting a Markov Chain Monte Carlo simulations. The model is used to estimate current \"true\" cases of infection and death. We analyze the future trajectory of the disease under six conditions related to the seasonal effects and policy measures targeting social distancing. Findings: The model closely replicates the past data but also shows the true number of cases is likely far larger. We estimate about 493,000 current infected cases (90% CI: 271K-810K) as of March 20th, 2020. Our estimate for cumulative cases of infection until that date is 916,000 (90% CI: 508K, 1.5M), and for total death is 15,485 (90% CI: 8.4K, 25.8K). These numbers are significantly (more than one order of magnitude) higher than official statistics. The trajectory of the epidemic until the end of June could take various paths depending on the impact of seasonality and policies targeting social distancing. In the most optimistic scenario for seasonal effects, depending on policy measures, 1.6 million Iranians (90% CI: 0.9M-2.6M) are likely to get infected, and death toll will reach about 58,000 cases (90% CI: 32K-97K), while in the more pessimistic scenarios, death toll may exceed 103,000 cases (90% CI: 56K-172K). Implication: Our results suggest that the number of cases and deaths may be over an order of magnitude larger than official statistics in Iran. Absent extended testing capacity other countries may face a significant under-count of existing cases and thus be caught off guard about the actual toll of the epidemic.", "qid": 8, "docid": "sflu2was", "rank": 38, "score": 8.523900032043457}, {"content": "Title: COVID-19: The unreasonable effectiveness of simple models Content: When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.", "qid": 8, "docid": "nda1toup", "rank": 39, "score": 8.496199607849121}, {"content": "Title: COVID-19: The unreasonable effectiveness of simple models Content: Abstract When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.", "qid": 8, "docid": "qf4v02lv", "rank": 40, "score": 8.496198654174805}, {"content": "Title: Using influenza surveillance networks to estimate state-specific prevalence of SARS-CoV-2 in the United States Content: Detection of SARS-CoV-2 infections to date has relied heavily on RT-PCR testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or sub-clinical infections have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how influenza-like illness (ILI) outpatient surveillance data can be used to estimate the prevalence of SARS-CoV-2. We found a surge of non-influenza ILI above the seasonal average in March 2020 and showed that this surge correlated with COVID-19 case counts across states. If 1/3 of patients infected with SARS-CoV-2 in the US sought care, this ILI surge would have corresponded to more than 8.7 million new SARS-CoV-2 infections across the US during the three-week period from March 8 to March 28, 2020. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to have been doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID-19 epidemic in the US characterized by rapid spread across the US with over 80% infected patients remaining undetected. We emphasize the importance of testing these findings with seroprevalence data and discuss the broader potential to use syndromic surveillance for early detection and understanding of emerging infectious diseases.", "qid": 8, "docid": "szvb2gsf", "rank": 41, "score": 8.490099906921387}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60-95%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood.", "qid": 8, "docid": "hsr2ue28", "rank": 42, "score": 8.480400085449219}, {"content": "Title: BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic? Content: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette-Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.", "qid": 8, "docid": "9mjyu55i", "rank": 43, "score": 8.454299926757812}, {"content": "Title: BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic? Content: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette\u2013Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.", "qid": 8, "docid": "reigmh19", "rank": 44, "score": 8.454298973083496}, {"content": "Title: Deep learning COVID-19 detection bias: accuracy through artificial intelligence Content: BACKGROUND: Detection of COVID-19 cases' accuracy is posing a conundrum for scientists, physicians, and policy-makers. As of April 23, 2020, 2.7 million cases have been confirmed, over 190,000 people are dead, and about 750,000 people are reported recovered. Yet, there is no publicly available data on tests that could be missing infections. Complicating matters and furthering anxiety are specific instances of false-negative tests. METHODS: We developed a deep learning model to improve accuracy of reported cases and to precisely predict the disease from chest X-ray scans. Our model relied on convolutional neural networks (CNNs) to detect structural abnormalities and disease categorization that were keys to uncovering hidden patterns. To do so, a transfer learning approach was deployed to perform detections from the chest anterior-posterior radiographs of patients. We used publicly available datasets to achieve this. RESULTS: Our results offer very high accuracy (96.3%) and loss (0.151 binary cross-entropy) using the public dataset consisting of patients from different countries worldwide. As the confusion matrix indicates, our model is able to accurately identify true negatives (74) and true positives (32); this deep learning model identified three cases of false-positive and one false-negative finding from the healthy patient scans. CONCLUSIONS: Our COVID-19 detection model minimizes manual interaction dependent on radiologists as it automates identification of structural abnormalities in patient's CXRs, and our deep learning model is likely to detect true positives and true negatives and weed out false positive and false negatives with > 96.3% accuracy.", "qid": 8, "docid": "4y13cc7f", "rank": 45, "score": 8.449299812316895}, {"content": "Title: Deep learning COVID-19 detection bias: accuracy through artificial intelligence Content: BACKGROUND: Detection of COVID-19 cases\u2019 accuracy is posing a conundrum for scientists, physicians, and policy-makers. As of April 23, 2020, 2.7 million cases have been confirmed, over 190,000 people are dead, and about 750,000 people are reported recovered. Yet, there is no publicly available data on tests that could be missing infections. Complicating matters and furthering anxiety are specific instances of false-negative tests. METHODS: We developed a deep learning model to improve accuracy of reported cases and to precisely predict the disease from chest X-ray scans. Our model relied on convolutional neural networks (CNNs) to detect structural abnormalities and disease categorization that were keys to uncovering hidden patterns. To do so, a transfer learning approach was deployed to perform detections from the chest anterior-posterior radiographs of patients. We used publicly available datasets to achieve this. RESULTS: Our results offer very high accuracy (96.3%) and loss (0.151 binary cross-entropy) using the public dataset consisting of patients from different countries worldwide. As the confusion matrix indicates, our model is able to accurately identify true negatives (74) and true positives (32); this deep learning model identified three cases of false-positive and one false-negative finding from the healthy patient scans. CONCLUSIONS: Our COVID-19 detection model minimizes manual interaction dependent on radiologists as it automates identification of structural abnormalities in patient\u2019s CXRs, and our deep learning model is likely to detect true positives and true negatives and weed out false positive and false negatives with > 96.3% accuracy.", "qid": 8, "docid": "c6d2vym9", "rank": 46, "score": 8.449298858642578}, {"content": "Title: Cancer therapy and treatments during COVID-19 era Content: The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.", "qid": 8, "docid": "i90x2r7t", "rank": 47, "score": 8.419300079345703}, {"content": "Title: Analysis of the sex ratio of reported gonorrhoea incidence in Shenzhen, China Content: OBJECTIVE: To assess the clinical process of gonorrhoea diagnosis and report in China, and to determine the difference of sex ratio between reported incidence based on reporting data and true diagnosis rate based on reference tests of gonorrhoea. SETTING: A total of 26 dermatology and sexually transmitted disease (STD) departments, 34 obstetrics-gynaecology clinics and 28 urology outpatient clinics selected from 34 hospitals of Shenzhen regarded as our study sites. PARTICIPANTS: A total of 2754 participants were recruited in this study, and 2534 participants completed the questionnaire survey and provided genital tract secretion specimens. There were 1106 male and 1428 female participants. Eligible participants were patients who presented for outpatient STD care at the selected clinics for the first time in October 2012 were at least 18 years old, and were able to give informed consent. OUTCOME MEASURES: Untested rate, true-positive rate, false-negative rate and unreported rate of gonorrhoea, as well as reported gonorrhoea incidence sex ratio and true diagnosis sex ratio were calculated and used to describe the results. RESULTS: 2534 participants were enrolled in the study. The untested rate of gonorrhoea among females was significantly higher than that among males (female 88.1%, male 68.3%, p=0.001). The male-to-female sex ratios of untested rate, true-positive rate, false-negative rate and unreported rate were 1:1.3, 1.2:1, 1:1.6 and 1:1.4, respectively. The reported gonorrhoea incidence sex ratio of new diagnosed gonorrhoea was 19.8:1 (male vs female: 87/1106 vs 5/1420), while the true diagnosis sex ratio was 2.5:1 (male vs female: 161/1106 vs 84/1420). These data indicate that the sex ratio of reported gonorrhoea incidence has been overestimated by a factor of 7.9 (19.8/2.5). CONCLUSIONS: We found the current reported gonorrhoea incidence and sex ratios to be inaccurate due to underestimations of gonorrhoea incidence, especially among women.", "qid": 8, "docid": "2smn2hl5", "rank": 48, "score": 8.411399841308594}, {"content": "Title: The \"true\" incidence of surgically treated deep prosthetic joint infection after 32,896 primary total hip arthroplasties: a prospective cohort study. Content: BACKGROUND AND PURPOSE It has been suggested that the risk of prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA) may be underestimated if based only on arthroplasty registry data. We therefore wanted to estimate the \"true\" incidence of PJI in THA using several data sources. PATIENTS AND METHODS We searched the Danish Hip Arthroplasty Register (DHR) for primary THAs performed between 2005 and 2011. Using the DHR and the Danish National Register of Patients (NRP), we identified first revisions for any reason and those that were due to PJI. PJIs were also identified using an algorithm incorporating data from microbiological, prescription, and clinical biochemistry databases and clinical findings from the medical records. We calculated cumulative incidence with 95% confidence interval. RESULTS 32,896 primary THAs were identified. Of these, 1,546 had first-time revisions reported to the DHR and/or the NRP. For the DHR only, the 1- and 5-year cumulative incidences of PJI were 0.51% (0.44-0.59) and 0.64% (0.51-0.79). For the NRP only, the 1- and 5-year cumulative incidences of PJI were 0.48% (0.41-0.56) and 0.57% (0.45-0.71). The corresponding 1- and 5-year cumulative incidences estimated with the algorithm were 0.86% (0.77-0.97) and 1.03% (0.87-1.22). The incidences of PJI based on the DHR and the NRP were consistently 40% lower than those estimated using the algorithm covering several data sources. INTERPRETATION Using several available data sources, the \"true\" incidence of PJI following primary THA was estimated to be approximately 40% higher than previously reported by national registries alone.", "qid": 8, "docid": "43l16iuc", "rank": 49, "score": 8.364999771118164}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 8, "docid": "ejsqsn59", "rank": 50, "score": 8.349200248718262}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 8, "docid": "lfjud2aq", "rank": 51, "score": 8.349199295043945}, {"content": "Title: Estimation of SARS-CoV-2 Infection Prevalence in Santa Clara County Content: To reliably estimate the demand on regional health systems and perform public health planning, it is necessary to have a good estimate of the prevalence of infection with SARS-CoV-2 (the virus that causes COVID-19) in the population. In the absence of wide-spread testing, we provide one approach to infer prevalence based on the assumption that the fraction of true infections needing hospitalization is fixed and that all hospitalized cases of COVID-19 in Santa Clara are identified. Our goal is to estimate the prevalence of SARS-CoV-2 infections, i.e. the true number of people currently infected with the virus, divided by the total population size. Our analysis suggests that as of March 17, 2020, there are 6,500 infections (0.34% of the population) of SARS-CoV-2 in Santa Clara County. Based on adjusting the parameters of our model to be optimistic (respectively pessimistic), the number of infections would be 1,400 (resp. 26,000), corresponding to a prevalence of 0.08% (resp. 1.36%). If the shelter-in-place led to R0 < 1, we would expect the number of infections to remain about constant for the next few weeks. However, even if this were true, we expect to continue to see an increase in hospitalized cases of COVID-19 in the short term due to the fact that infection of SARS-CoV-2 on March 17th can lead to hospitalizations up to 14 days later.", "qid": 8, "docid": "6vt60348", "rank": 52, "score": 8.347200393676758}, {"content": "Title: Is there evidence that BCG vaccination has non-specific protective effects for COVID 19 infections or is it an illusion created by lack of testing? Content: The goal of this paper is to showcase that the COVID-19 disease pattern is evolving and to study the relationship between mandatory BCG policy and caseload/million or death/per million. We analyze seven recent publications on the impact of BCG vaccinations on the development of COVID19 illness and extend presented findings using the latest data from April 10, 2020. We analyze data from 98 countries and we extend existing models by adding the dimension of COVID-19-related testing conducted by the analyzed countries. Similarly to prior studies, we find that COVID-19 attributable case and death incidences across countries share a relationship with the BCG vaccination inclusion in the national immunization program of a country when testing is not taken into consideration. However, this relationship vanishes when we add the dimension of testing. We observe that case and death incidences conditional on testing do not get affected by the BCG vaccination inclusion in the national immunization program of a country. Therefore, we show that there is no statistical evidence to support the assertion that inclusion of BCG vaccination in national immunization program (NIP) has any impact of COVID 19 infections (cases) or mortality.", "qid": 8, "docid": "he8mcvn8", "rank": 53, "score": 8.342499732971191}, {"content": "Title: Nonsurgical Rhinoplasty: A Systematic Review of Technique, Outcomes, and Complications. Content: BACKGROUND Nonsurgical rhinoplasty using filler injections has become a common procedure in cosmetic practices. This is offered to patients that prefer a temporary outcome or would like to avoid general anesthesia. In addition, it can be used in postrhinoplasty patients to correct nasal deformities or irregularities. This systematic review highlights common filler types and injection techniques, and associated patient satisfaction and complications to further guide practitioners. METHODS A systematic review was performed using keywords and Medical Subject Headings search terms. PubMed, EmBase, the Cochrane Library, and Scopus were searched using the appropriate search terms. Data collected from each study included patient satisfaction and complications, in addition to injection material, location, and technique. RESULTS Four thousand six hundred thirty-two studies were found based on search criteria. After full-text screening for inclusion and exclusion criteria, 23 studies were included. A total of 1600 patients underwent nonsurgical rhinoplasty, most commonly with hyaluronic acid (73.38 percent), followed by calcium hydroxyapatite (12.44 percent). Nearly 95 percent of patients were satisfied with results, and there were only 26 relatively minor complications reported. There were no reports of vascular complications such as skin necrosis or visual compromise. CONCLUSIONS Based on the authors' review of the literature, nonsurgical rhinoplasty is an effective temporary alternative to traditional augmentation rhinoplasty for corrections of nasal shape with a high degree of patient satisfaction. Complications may be underreported, and thus further investigation is needed to better understand the true incidence of major complications related to vascular compromise.", "qid": 8, "docid": "2pg4hrpy", "rank": 54, "score": 8.31089973449707}, {"content": "Title: The COVID-19 (SARS-CoV-2) Uncertainty Tripod in Brazil: Assessments on model-based predictions with large under-reporting Content: The COVID-19 pandemic (SARS-CoV-2 virus) is the defying global health crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We propose an adapted Susceptible-Infected-Recovered (SIR) model which explicitly incorporates the under-reporting and the response of the population to public policies (such as confinement measures, widespread use of masks, etc) to cast short-term and long-term predictions. Large amounts of uncertainty could provide misleading models and predictions. In this paper, we discuss the role of uncertainty in these prediction, which is illustrated regarding three key aspects. First, assuming that the number of infected individuals is under-reported, we demonstrate an anticipation regarding the peak of infection. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic. Second, considering that the actual amount of deaths is larger than what is being register, then demonstrate the increase of the mortality rates. Third, when consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the effect of the\"COVID-19 under-reporting tripod\", i.e. the under-reporting in terms of infected individuals, of deaths and the true mortality rate. If two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates.", "qid": 8, "docid": "8cw3bjxh", "rank": 55, "score": 8.308899879455566}, {"content": "Title: Hemogram data as a tool for decision-making in COVID-19 management: applications to resource scarcity scenarios Content: BACKGROUND: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. PURPOSE: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. METHODS: Hemogram exams data from 510 symptomatic patients (73 positives and 437 negatives) were used to model and predict qRT-PCR results through Na\u00efve-Bayes algorithms. Different scarcity scenarios were simulated, including symptomatic essential workforce management and absence of diagnostic tests. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. RESULTS: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity, yielding a 100% sensitivity and 22.6% specificity with a prior of 0.9999; 76.7% for both sensitivity and specificity with a prior of 0.2933; and 0% sensitivity and 100% specificity with a prior of 0.001. Regarding background scarcity context, resources allocation can be significantly improved when model-based patient selection is observed, compared to random choice. CONCLUSIONS: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.", "qid": 8, "docid": "jcyq8qve", "rank": 56, "score": 8.27910041809082}, {"content": "Title: Elective, Non-urgent Procedures and Aesthetic Surgery in the Wake of SARS-COVID-19: Considerations Regarding Safety, Feasibility and Impact on Clinical Management Content: BACKGROUND: The worldwide spread of a novel coronavirus disease (COVID-19) has led to a near total stop of non-urgent, elective surgeries across all specialties in most affected countries. In the field of aesthetic surgery, the self-imposed moratorium for all aesthetic surgery procedures recommended by most international scientific societies has been adopted by many surgeons worldwide and resulted in a huge socioeconomic impact for most private practices and clinics. An important question still unanswered in most countries is when and how should elective/aesthetic procedures be scheduled again and what kind of organizational changes are necessary to protect patients and healthcare workers when clinics and practices reopen. Defining manageable, evidence-based protocols for testing, surgical/procedural risk mitigation and clinical flow management/contamination management will be paramount for the safety of non-urgent surgical procedures. METHODS: We conducted a MEDLINE/PubMed research for all available publications on COVID-19 and surgery and COVID-19 and anesthesia. Articles and referenced literature describing possible procedural impact factors leading to exacerbation of the clinical evolution of COVID-19-positive patients were identified to perform risk stratification for elective surgery. Based on these impact factors, considerations for patient selection, choice of procedural complexity, duration of procedure, type of anesthesia, etc., are discussed in this article and translated into algorithms for surgical/anesthesia risk management and clinical management. Current recommendations and published protocols on contamination control, avoidance of cross-contamination and procedural patient flow are reviewed. A COVID-19 testing guideline protocol for patients planning to undergo elective aesthetic surgery is presented and recommendations are made regarding adaptation of current patient information/informed consent forms and patient health questionnaires. CONCLUSION: The COVID-19 crisis has led to unprecedented challenges in the acute management of the crisis, and the wave only recently seems to flatten out in some countries. The adaptation of surgical and procedural steps for a risk-minimizing management of potential COVID-19-positive patients seeking to undergo elective aesthetic procedures in the wake of that wave will present the next big challenge for the aesthetic surgery community. We propose a clinical algorithm to enhance patient safety in elective surgery in the context of COVID-19 and to minimize cross-contamination between healthcare workers and patients. New evidence-based guidelines regarding surgical risk stratification, testing, and clinical flow management/contamination management are proposed. We believe that only the continuous development and broad implementation of guidelines like the ones proposed in this paper will allow an early reintegration of all aesthetic procedures into the scope of surgical care currently performed and to prepare the elective surgical specialties better for a possible second wave of the pandemic. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.", "qid": 8, "docid": "dtnc7x6a", "rank": 57, "score": 8.274100303649902}, {"content": "Title: Elective, Non-urgent Procedures and Aesthetic Surgery in the Wake of SARS\u2013COVID-19: Considerations Regarding Safety, Feasibility and Impact on Clinical Management Content: BACKGROUND: The worldwide spread of a novel coronavirus disease (COVID-19) has led to a near total stop of non-urgent, elective surgeries across all specialties in most affected countries. In the field of aesthetic surgery, the self-imposed moratorium for all aesthetic surgery procedures recommended by most international scientific societies has been adopted by many surgeons worldwide and resulted in a huge socioeconomic impact for most private practices and clinics. An important question still unanswered in most countries is when and how should elective/aesthetic procedures be scheduled again and what kind of organizational changes are necessary to protect patients and healthcare workers when clinics and practices reopen. Defining manageable, evidence-based protocols for testing, surgical/procedural risk mitigation and clinical flow management/contamination management will be paramount for the safety of non-urgent surgical procedures. METHODS: We conducted a MEDLINE/PubMed research for all available publications on COVID-19 and surgery and COVID-19 and anesthesia. Articles and referenced literature describing possible procedural impact factors leading to exacerbation of the clinical evolution of COVID-19-positive patients were identified to perform risk stratification for elective surgery. Based on these impact factors, considerations for patient selection, choice of procedural complexity, duration of procedure, type of anesthesia, etc., are discussed in this article and translated into algorithms for surgical/anesthesia risk management and clinical management. Current recommendations and published protocols on contamination control, avoidance of cross-contamination and procedural patient flow are reviewed. A COVID-19 testing guideline protocol for patients planning to undergo elective aesthetic surgery is presented and recommendations are made regarding adaptation of current patient information/informed consent forms and patient health questionnaires. CONCLUSION: The COVID-19 crisis has led to unprecedented challenges in the acute management of the crisis, and the wave only recently seems to flatten out in some countries. The adaptation of surgical and procedural steps for a risk-minimizing management of potential COVID-19-positive patients seeking to undergo elective aesthetic procedures in the wake of that wave will present the next big challenge for the aesthetic surgery community. We propose a clinical algorithm to enhance patient safety in elective surgery in the context of COVID-19 and to minimize cross-contamination between healthcare workers and patients. New evidence-based guidelines regarding surgical risk stratification, testing, and clinical flow management/contamination management are proposed. We believe that only the continuous development and broad implementation of guidelines like the ones proposed in this paper will allow an early reintegration of all aesthetic procedures into the scope of surgical care currently performed and to prepare the elective surgical specialties better for a possible second wave of the pandemic. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.", "qid": 8, "docid": "x6drl82v", "rank": 58, "score": 8.274099349975586}, {"content": "Title: Quantifying spatiotemporal heterogeneity of MERS-CoV transmission in the Middle East region: A combined modelling approach Content: Abstract MERS coronavirus cases notified in the Middle East region since the identification of the virus in 2012 have displayed variations in time and across geography. Through a combined modelling approach, we estimate the rates of generation of cases along the zoonotic and human-to-human transmission routes and assess their spatiotemporal heterogeneity. We consider all cases notified to WHO from March 2012 to mid-September 2014. We use a stochastic modelling of the time series of case incidence in the Middle East region to estimate time- and space-dependent zoonotic and human-to-human transmission parameters. The model also accounts for possible lack of identification of secondary transmissions among notified cases. This approach is combined with the analysis of imported cases out of the region to assess the rate of underreporting of cases. Out of a total of 32 possible models, based on different parameterisation and scenario considered, the best-fit model is characterised by a large heterogeneity in time and across space for both zoonotic and human-to-human transmission. The variation in time that occurred during Spring 2014 led to a 17-fold and 3-fold increase in the two transmissions, respectively, bringing the reproductive rate to values above 1 during that period for all regions under study. The model suggests that 75% of MERS-CoV cases are secondary cases (human-to-human transmission), which is substantially higher than the 34% of reported cases with an epidemiological link to another case. Overall, estimated reporting rate is 0.26. Our findings show a higher level of spatial heterogeneity in zoonotic transmission compared to human-to-human, highlighting the strong environmental component of the epidemic. Since sporadic introductions are predicted to be a small proportion of notified cases and are responsible for triggering secondary transmissions, a more comprehensive understanding of zoonotic source and path of transmission could be critical to limit the epidemic spread.", "qid": 8, "docid": "qejtarkd", "rank": 59, "score": 8.267499923706055}, {"content": "Title: Covid-19: Pandemonium in our time. Content: While pandemonium has come to mean wild and noisy disorder, the reference here is to John Milton's epic poem Paradise Lost and the upheaval following Lucifer's banishment from Heaven and his construction of Pand\u00e6monium as his hub. Today's avalanche of conflicting news on how to deal with the coronavirus disease 2019 (Covid-19) brings to mind the Trinity nuclear bomb test with Enrico Fermi estimating its strength by releasing small pieces of paper into the air and measuring their displacement by the shock wave. Fermi's result, in fact not far from the true value, emphasised his ability to make good approximations with few or no actual data. The current wave of Covid-19 presents just this kind of situation as it engulfs the world from ground zero in Wuhan, China. Much information is indeed missing, but datasets that might lead to useful ideas on how to handle this pandemic are steadily accumulating.", "qid": 8, "docid": "89slu3rr", "rank": 60, "score": 8.222700119018555}, {"content": "Title: Covid-19: Pandemonium in our time Content: While pandemonium has come to mean wild and noisy disorder, the reference here is to John Milton's epic poem Paradise Lost and the upheaval following Lucifer's banishment from Heaven and his construction of Pand\u00e6monium as his hub. Today's avalanche of conflicting news on how to deal with the coronavirus disease 2019 (Covid-19) brings to mind the Trinity nuclear bomb test with Enrico Fermi estimating its strength by releasing small pieces of paper into the air and measuring their displacement by the shock wave. Fermi's result, in fact not far from the true value, emphasised his ability to make good approximations with few or no actual data. The current wave of Covid-19 presents just this kind of situation as it engulfs the world from ground zero in Wuhan, China. Much information is indeed missing, but datasets that might lead to useful ideas on how to handle this pandemic are steadily accumulating.", "qid": 8, "docid": "ntx2c04x", "rank": 61, "score": 8.222699165344238}, {"content": "Title: Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase Content: Abstract The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.", "qid": 8, "docid": "0nqz5y20", "rank": 62, "score": 8.19950008392334}, {"content": "Title: Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase Content: The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.", "qid": 8, "docid": "jznszeo7", "rank": 63, "score": 8.199499130249023}, {"content": "Title: Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches Content: Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.", "qid": 8, "docid": "4i0gici7", "rank": 64, "score": 8.174799919128418}, {"content": "Title: COVID-19, Australia: Epidemiology Report 16 (Reporting week to 23:59 AEST 17 May 2020). Content: Confirmed cases in Australia notified up to 17 May 2020: notifications = 7,075; deaths = 100. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. Social distancing measures, public health action and the reduction in international travel have likely been effective in slowing the spread of the disease, in the Australian community. Testing rates over the past week have increased markedly, with a continued very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. New cases of COVID-19 are currently being reported by by only some jurisdictions, albeit at relatively low rates. Although case numbers are low, new cases tend to still be a mix of overseas-acquired and locally-acquired infections. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of new cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years. One third of all cases in this age group have been associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, while the number of new cases each day remains relatively stable at the global level, some areas such as Brazil and India are showing a dramatic rise in reported cases. Although some low-income countries have so far reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of true disease incidence.", "qid": 8, "docid": "8cw12q7i", "rank": 65, "score": 8.163999557495117}, {"content": "Title: COVID-19, Australia: Epidemiology Report 16 (Reporting week to 23:59 AEST 17 May 2020) Content: Confirmed cases in Australia notified up to 17 May 2020: notifications = 7,075; deaths = 100. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. Social distancing measures, public health action and the reduction in international travel have likely been effective in slowing the spread of the disease, in the Australian community. Testing rates over the past week have increased markedly, with a continued very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. New cases of COVID-19 are currently being reported by by only some jurisdictions, albeit at relatively low rates. Although case numbers are low, new cases tend to still be a mix of overseas-acquired and locally-acquired infections. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of new cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years. One third of all cases in this age group have been associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, while the number of new cases each day remains relatively stable at the global level, some areas such as Brazil and India are showing a dramatic rise in reported cases. Although some low-income countries have so far reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of true disease incidence.", "qid": 8, "docid": "megipjpn", "rank": 66, "score": 8.1639986038208}, {"content": "Title: Fever and mobility data indicate social distancing has reduced incidence of communicable disease in the United States Content: In March of 2020, many U.S. state governments encouraged or mandated restrictions on social interactions to slow the spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2 that has spread to nearly 180 countries. Estimating the effectiveness of these social-distancing strategies is challenging because surveillance of COVID-19 has been limited, with tests generally being prioritized for high-risk or hospitalized cases according to temporally and regionally varying criteria. Here we show that reductions in mobility across U.S. counties with at least 100 confirmed cases of COVID-19 led to reductions in fever incidences, as captured by smart thermometers, after a mean lag of 6.5 days ($90\\%$ within 3--10 days) that is consistent with the incubation period of COVID-19. Furthermore, counties with larger decreases in mobility subsequently achieved greater reductions in fevers ($p<0.01$), with the notable exception of New York City and its immediate vicinity. These results indicate that social distancing has reduced the transmission of influenza like illnesses, including COVID 19, and support social distancing as an effective strategy for slowing the spread of COVID-19.", "qid": 8, "docid": "cb5ebiiv", "rank": 67, "score": 8.162699699401855}, {"content": "Title: COVID-19 Clinical Trial Oversight at a Major Academic Medical Center: Approach of the Michigan Medicine COVID-19 Clinical Trial Committees Content: Clinicians - eager to offer the best care in the absence of guiding data - have provided patients with COVID-19 diverse clinical interventions. This usage has led to perceptions of efficacy of some interventions that, while receiving media coverage, lack robust evidence. Moving forward, randomized controlled clinical trials (RCTs) are necessary to ensure that clinicians can treat patients effectively during this outbreak and the next. To do so, academic medical centers must address two key research issues: (1) how to effectively and efficiently determine which trials have the best chance of benefiting current and future patients, and (2) how to establish a transparent and ethical process for subject recruitment while maintaining research integrity and without overburdening patients or staff. We share here the current methods used by the University of Michigan to address these issues.", "qid": 8, "docid": "j9zd827k", "rank": 68, "score": 8.159199714660645}, {"content": "Title: COVID-19 Clinical Trial Oversight at a Major Academic Medical Center: Approach of the Michigan Medicine COVID-19 Clinical Trial Committees Content: Clinicians \u2013 eager to offer the best care in the absence of guiding data \u2013 have provided patients with COVID-19 diverse clinical interventions. This usage has led to perceptions of efficacy of some interventions that, while receiving media coverage, lack robust evidence. Moving forward, randomized controlled clinical trials (RCTs) are necessary to ensure that clinicians can treat patients effectively during this outbreak and the next. To do so, academic medical centers must address two key research issues: (1) how to effectively and efficiently determine which trials have the best chance of benefiting current and future patients, and (2) how to establish a transparent and ethical process for subject recruitment while maintaining research integrity and without overburdening patients or staff. We share here the current methods used by the University of Michigan to address these issues.", "qid": 8, "docid": "mb0ceyq7", "rank": 69, "score": 8.159198760986328}, {"content": "Title: COVID-19 (SARS-CoV-2) Ventilator Resource Management Using a Network Optimization Model and Predictive System Demand Content: The COVID-19 (SARS-CoV-2) pandemic is overwhelming global healthcare delivery systems due to the exponential spike in cases requiring specialty tests, facilities and equipment, including complex, precision devices like ventilators. In particular, the surge in critically ill patients has revealed a significant deficiency in regional availability of respiratory care ventilators. The authors offer a mathematical framework for ventilator distribution under scarcity conditions using an optimized network model and solver. The framework is interoperable with existing COVID-19 healthcare demand models and scales for different user-defined system sizes, including hospital networks, city, state, regional and national-scale prioritization. The authors' approach improves current capabilities for medical device resource management within the existing incident command system while accounting for availability of devices, ventilation treatment time periods, disinfection and cleaning between patients, as well as shipping logistics time. The authors present a proof of concept using a high fidelity COVID-19 data set from Colorado, discusses how to scale nationally, and emphasizes the importance of applying ethical human-in-the-loop decision making when using this or similar approaches to managing medical device resources during epidemic emergencies.", "qid": 8, "docid": "pia8gbon", "rank": 70, "score": 8.139800071716309}, {"content": "Title: \u2018These are answers we need.\u2019 WHO plans global study to discover true extent of coronavirus infections Content: In an effort to understand how many people have been infected with the new coronavirus, the World Health Organization (WHO) is planning a coordinated study to test blood samples for the presence of antibodies to the virus Called Solidarity II, the program, which will involve more than half a dozen countries around the globe, will launch in the coming days, says Maria Van Kerkhove, who is helping coordinate WHO\u2019s COVID-19 response Knowing the true number of cases\u2014including mild ones\u2014will help pin down the prevalence and mortality rate of COVID-19 in different age groups It will also help policymakers decide how long shutdowns and quarantines should last \u201cThese are answers we need, and we need the right answers to drive policy,\u201d WHO\u2019s executive director for health emergencies, Michael Ryan, told a press briefing on 27 March", "qid": 8, "docid": "0klg8yvs", "rank": 71, "score": 8.121700286865234}, {"content": "Title: The need for COVID-19 research in low- and middle-income countries Content: In the early months of the pandemic, most reported cases and deaths due to COVID-19 occurred in high-income countries. However, insufficient testing could have led to an underestimation of true infections in many low- and middle-income countries. As confirmed cases increase, the ultimate impact of the pandemic on individuals and communities in low- and middle-income countries is uncertain. We therefore propose research in three broad areas as urgently needed to inform responses in low- and middle-income countries: transmission patterns of SARS-CoV-2, the clinical characteristics of the disease, and the impact of pandemic prevention and response measures. Answering these questions will require a multidisciplinary approach led by local investigators and in some cases additional resources. Targeted research activities should be done to help mitigate the potential burden of COVID-19 in low- and middle-income countries without diverting the limited human resources, funding, or medical supplies from response activities.", "qid": 8, "docid": "uzrxtgrg", "rank": 72, "score": 8.103300094604492}, {"content": "Title: Predicting Whom to Test is More Important Than More Tests - Modeling the Impact of Testing on the Spread of COVID-19 Virus By True Positive Rate Estimation Content: I estimate plausible true positive (TP) rates for the number of COVID-19 tests per day, most relevant when the number of test is on the same order of magnitude as number of infected persons. I then modify a standard SEIR model to model current growth patterns and detection rates in South Korea and New York state. Although reducing transmission rates have the largest impact, increasing TP rates by ~10% in New York can have an impact equal to adding tens of thousands of new tests per day. Increasing both TP rates and tests per day together can have significant impacts and likely be more easily sustained than social distancing restrictions. Systematic and standardized data collection, even beyond contact tracking, should be ongoing and quickly made available for research teams to maximize the efficacy of testing.", "qid": 8, "docid": "06vc2y9y", "rank": 73, "score": 8.088600158691406}, {"content": "Title: Trends in excess cancer and cardiovascular deaths in Scotland during the COVID-19 pandemic 30 December 2019 to 20 April 2020 Content: Understanding the trends in causes of death for different diseases during the current COVID-19 pandemic is important to determine whether there are excess deaths beyond what is normally expected. Using the most recent report from National Records Scotland (NRS) on 29 April 2020, we examined the percentage difference in crude numbers of deaths in 2020 compared to the average for 2015-2019 by week of death within calendar year. To determine if trends were similar, suggesting underreporting/underdiagnosed COVID-19 related deaths, we also looked at the trends in % differences for cardiovascular disease deaths. From the first 17 weeks' of data, we found a peak in excess deaths between weeks 14 of 2020, about four weeks after the first case in Scotland was detected on 1 March 2020-- but by week 17 these excesses had diminished around the time lockdown in the UK began. Similar observations were seen for cardiovascular disease-related deaths. These observations suggest that the short-term increase in excess cancer and cardiovascular deaths might be associated with undetected/unconfirmed deaths related to COVID-19. Both of these conditions make patients more susceptible to infection and lack of widespread access to testing for COVID-19 are likely to have resulted in under-estimation of COVID-19 mortality. These data further suggest that the cumulative toll of COVID-19 on mortality is likely undercounted. More detailed analysis is needed to determine if these excesses were directly or indirectly related to COVID-19. Disease specific mortality will need constant monitoring for the foreseeable future as changes occur in increasing capacity and access to testing, reporting criteria, changes to health services and different measures are implemented to control the spread of the COVID-19. Multidisciplinary, multi-institutional, national and international collaborations for complementary and population specific data analysis is required to respond and mitigate adverse effects of the COVID-19 pandemic and to inform planning for future pandemics.", "qid": 8, "docid": "223v2obv", "rank": 74, "score": 8.050399780273438}, {"content": "Title: COVID- 19 Infection in Children: Estimating Pediatric Morbidity and Mortality Content: BACKGROUND: Estimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic. METHODS: Government websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series. RESULTS: Data on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases. CONCLUSION: Children accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.", "qid": 8, "docid": "71uvferq", "rank": 75, "score": 8.050299644470215}, {"content": "Title: New statistical model for misreported data with application to current public health challenges Content: The main goal of this work is to present a new model able to deal with potentially misreported continuous time series. The proposed model is able to handle the autocorrelation structure in continuous time series data, which might be partially or totally underreported or overreported. Its performance is illustrated through a comprehensive simulation study considering several autocorrelation structures and two real data applications on human papillomavirus incidence in Girona (Catalunya, Spain) and COVID-19 incidence in the Chinese region of Heilongjiang.", "qid": 8, "docid": "x51cdraa", "rank": 76, "score": 8.036399841308594}, {"content": "Title: The Potential Impacts of Pandemic Policing on Police Legitimacy: Planning Past the COVID-19 Crisis Content: One of the biggest challenges facing modern policing in recent years has been the lack of police legitimacy. The tipping point of this phenomenon is often attributed to the Rodney King incident in Los Angeles in 1991, where Los Angeles Police Department (LAPD) officers were videoed assaulting a lone black male. They were arrested and charged but eventually all were acquitted, thereby etching deep distrust between communities and police. Now the Rodney King example is an extreme and criminal act by police but it was the beginning of communities and media focusing on what the police were doing and how they were doing it. This lack of legitimacy coupled with what is referred to as the militarization of policing have lasting consequences and impacts on police\u2013community relations and how interactions between police and community shape society today. In the wake of pandemic policing due to COVID-19, there are tales of two eventualities for police legitimacy that will be explored in this article: (1) The police response to the pandemic results in further militarization and draws deeper divides between police and communities or (2) the police response is compassionate and build on procedurally just operations resulting in the rebuilding of police legitimacy post-pandemic.", "qid": 8, "docid": "jxxcvbna", "rank": 77, "score": 8.022500038146973}, {"content": "Title: Risk of secondary infection waves of COVID-19 in an insular region: the case of the Balearic Islands, Spain Content: The Spanish government declared the lockdown on March 14th, 2020 to tackle the fast-spreading of COVID-19. As a consequence the Balearic Islands remained almost fully isolated due to the closing of airports and ports, These isolation measures and the home-based confinement have led to a low incidence of COVID-19 in this region. We propose a compartmental model for the spread of COVID-19 including five compartments (Susceptible, Latent, Infected, Diseased, and Recovered), and the mobility between municipalities. The model parameters are calibrated with the temporal series of confirmed cases provided by the Spanish Ministry of Health. After calibration, the proposed model captures the trend of the official confirmed cases before and after the lockdown. We show that the estimated number of cases depends strongly on the initial dates of the local outbreak onset and the number of imported cases before the lockdown. Our estimations indicate that the population has not reached the level of herd immunization necessary to prevent future outbreaks. While the low incidence, in comparison to mainland Spain, has prevented the saturation of the health system, this low incidence translates into low immunization rates, therefore facilitating the propagation of new outbreaks that could lead to secondary waves of COVID-19 in the region. These findings warn about scenarios regarding after-lockdown-policies and the risk of second outbreaks, emphasize the need for widespread testing, and could potentially be extrapolated to other insular and continental regions.", "qid": 8, "docid": "glu5xlsd", "rank": 78, "score": 8.011899948120117}, {"content": "Title: Are coinfections with COVID-19 and influenza low or underreported? An observational study examining current published literature including three new unpublished cases Content: As the coronavirus disease-2019 (COVID-19) pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020 to 2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, TX, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of 13 patients described therein. Three additional patients were identified from the El Paso, TX data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome. The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens.", "qid": 8, "docid": "m7qoy6yq", "rank": 79, "score": 8.000100135803223}, {"content": "Title: Prevalence of acute liver injury and hypertransaminemia in patients with COVID-19: a protocol for a systematic review Content: INTRODUCTION: COVID-19 has spread rapidly in China and around the world. Published studies have revealed that some patients with COVID-19 had abnormal liver function in laboratory tests. However, the results were inconsistent and the analysis of epidemiological data stratified by the severity of COVID-19 was not available in previous meta-analyses. Furthermore, these meta-analyses were suspected of overestimating the incidence of liver injury in patients with COVID-19 because some studies considered transaminase elevation as liver injury, which might partially result from cardiac and muscle injury. This systematic review aims to enrol published literatures related to COVID-19 without language restriction, analyse the data based on the severity of the COVID-19 and explore the impact of varied definitions of liver injury on the incidence of liver injury. METHODS AND ANALYSIS: We have conducted a preliminary search on PubMed and Excerpta Medica Database on 13 April 2020, for the studies published after December 2019 on the prevalence of acute liver injury and hypertransaminemia in patients with COVID-19. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will estimate the pooled incidence of hypertransaminemia and acute liver injury in patients with COVID-19 by using the random-effects model. The I(\u00b2) test will be used to identify the extent of heterogeneity. Publication bias will be assessed by funnel plot and performing the Begg\u2019s and Egger\u2019s test if adequate studies are available. We will perform a risk of bias assessment using the Joanna Briggs Institute\u2019s critical appraisal checklist. ETHICS AND DISSEMINATION: Since this study will be based on the published data, it does not require ethical approval. The final results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020179462.", "qid": 8, "docid": "6dln5kww", "rank": 80, "score": 7.987100124359131}, {"content": "Title: Prevalence of acute liver injury and hypertransaminemia in patients with COVID-19: a protocol for a systematic review Content: INTRODUCTION: COVID-19 has spread rapidly in China and around the world. Published studies have revealed that some patients with COVID-19 had abnormal liver function in laboratory tests. However, the results were inconsistent and the analysis of epidemiological data stratified by the severity of COVID-19 was not available in previous meta-analyses. Furthermore, these meta-analyses were suspected of overestimating the incidence of liver injury in patients with COVID-19 because some studies considered transaminase elevation as liver injury, which might partially result from cardiac and muscle injury. This systematic review aims to enrol published literatures related to COVID-19 without language restriction, analyse the data based on the severity of the COVID-19 and explore the impact of varied definitions of liver injury on the incidence of liver injury. METHODS AND ANALYSIS: We have conducted a preliminary search on PubMed and Excerpta Medica Database on 13 April 2020, for the studies published after December 2019 on the prevalence of acute liver injury and hypertransaminemia in patients with COVID-19. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will estimate the pooled incidence of hypertransaminemia and acute liver injury in patients with COVID-19 by using the random-effects model. The I\u00b2 test will be used to identify the extent of heterogeneity. Publication bias will be assessed by funnel plot and performing the Begg's and Egger's test if adequate studies are available. We will perform a risk of bias assessment using the Joanna Briggs Institute's critical appraisal checklist. ETHICS AND DISSEMINATION: Since this study will be based on the published data, it does not require ethical approval. The final results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020179462.", "qid": 8, "docid": "otio8uzt", "rank": 81, "score": 7.9870991706848145}, {"content": "Title: Discrepancies between guidelines and clinical practice regarding prostate-specific antigen testing. Content: BACKGROUND Most guidelines recommend a judicious use of prostate-specific antigen (PSA) testing, whereas in daily practice, an increase of the incidence of PSA testing has been shown. Accurate up-to-date PSA test incidence rates are, however, lacking. OBJECTIVE To investigate the PSA test incidence rates in general practices over the past 10 years and to study which factors are associated with more frequent test use. METHODS We performed a retrospective cohort study using the routine health care database of the Julius General Practitioners Network from 2002 to 2011, of which data were available from more than 65 000 male patients. We calculated the annual incidence of PSA testing rates per 1000 person-years. Co-morbidities were analysed by means of International Classification of Primary Care codes. Relative risks (RRs) of having a PSA test were estimated as the ratio of observed rates of co-morbidities in men who underwent the test compared with a control group, and 95% confidence intervals (CI) were calculated. RESULTS From 2002 to 2011, the overall incidence rate of PSA testing in men \u226545 years increased almost 4-fold, from 15.5 to 54.3 per 1000 person-years. As from 2005, the incidence rates appear to increase more than those before 2005. Men with cardiovascular diseases, joint disorders, psychiatric diseases, respiratory diseases, overweight and diabetes mellitus were predisposed to undergo a PSA test, but men with urinary problems had the highest relative risk (RR 1.77, 95% CI 1.72-1.82). CONCLUSIONS From 2002 to 2011, PSA incidence testing rates increased, particularly in men with urinary symptoms and cardiovascular disease, despite several international guidelines that suggest a judicious use of PSA tests.", "qid": 8, "docid": "thyi3cbk", "rank": 82, "score": 7.979599952697754}, {"content": "Title: Momentum Contrastive Learning for Few-Shot COVID-19 Diagnosis from Chest CT Images Content: The current pandemic, caused by the outbreak of a novel coronavirus (COVID-19) in December 2019, has led to a global emergency that has significantly impacted economies, healthcare systems and personal wellbeing all around the world. Controlling the rapidly evolving disease requires highly sensitive and specific diagnostics. While real-time RT-PCR is the most commonly used, these can take up to 8 hours, and require significant effort from healthcare professionals. As such, there is a critical need for a quick and automatic diagnostic system. Diagnosis from chest CT images is a promising direction. However, current studies are limited by the lack of sufficient training samples, as acquiring annotated CT images is time-consuming. To this end, we propose a new deep learning algorithm for the automated diagnosis of COVID-19, which only requires a few samples for training. Specifically, we use contrastive learning to train an encoder which can capture expressive feature representations on large and publicly available lung datasets and adopt the prototypical network for classification. We validate the efficacy of the proposed model in comparison with other competing methods on two publicly available and annotated COVID-19 CT datasets. Our results demonstrate the superior performance of our model for the accurate diagnosis of COVID-19 based on chest CT images.", "qid": 8, "docid": "724br56j", "rank": 83, "score": 7.926799774169922}, {"content": "Title: Building a Multi-Institutional and Interdisciplinary Team to Develop a Zoonotic Tuberculosis Roadmap Content: Tuberculosis (TB), as the major infectious disease in the world, has devastating consequences for not only humans, but also cattle and several wildlife species. This disease presents additional challenges to human and veterinary health authorities given the zoonotic nature of the pathogens responsible for the disease across species. One of the main public health challenges regarding zoonotic TB (ZTB) caused by Mycobacterium bovis is that the true incidence of this type of TB in humans is not known and is likely to be underestimated. To effectively address challenges posed by ZTB, an integrated One Health approach is needed. In this manuscript, we describe the rationale, major steps, timeline, stakeholders, and important events that led to the assembling of a true integrated multi-institutional and interdisciplinary team that accomplished the ambitious goal of developing a ZTB roadmap, published in October, 2017. It outlines key activities to address the global challenges regarding the prevention, surveillance, diagnosis, and treatment of ZTB. We discuss and emphasize the importance of integrated approaches to be able to accomplish the short (year 2020) and medium term (year 2025) goals outlined in the ZTB roadmap.", "qid": 8, "docid": "h06876ok", "rank": 84, "score": 7.901599884033203}, {"content": "Title: An Evolving Approach to the Laboratory Assessment of COVID-19 Content: As the COVID-19 outbreak has evolved in each country, the approach to the laboratory assessment of SARS-CoV-2 infection has had to evolve as well. This review addresses the evolving approach to the laboratory assessment of COVID-19 and discusses how algorithms for testing have been driven, in part, by the demand for testing overwhelming the capacity to accomplish such testing. This review focused on testing in the United States as this testing is evolving whereas in China and other countries such as South Korea testing is widely available and includes both molecular testing for SARS-CoV-2 as well as serological testing using both ELISA methodology and lateral flow immunoassay methodology. Although commercial testing systems are becoming available, there will likely be insufficient numbers of such tests due to high demand. Serological testing will be the next testing issue as the COVID-19 begins to subside. This will allow immunity testing as well as will allow the parameters of the COVID-19 outbreak to be defined. This article is protected by copyright. All rights reserved.", "qid": 8, "docid": "k0f8jj0c", "rank": 85, "score": 7.89769983291626}, {"content": "Title: An Evolving Approach to the Laboratory Assessment of COVID\u201019 Content: As the COVID\u201019 outbreak has evolved in each country, the approach to the laboratory assessment of SARS\u2010CoV\u20102 infection has had to evolve as well. This review addresses the evolving approach to the laboratory assessment of COVID\u201019 and discusses how algorithms for testing have been driven, in part, by the demand for testing overwhelming the capacity to accomplish such testing. This review focused on testing in the United States as this testing is evolving whereas in China and other countries such as South Korea testing is widely available and includes both molecular testing for SARS\u2010CoV\u20102 as well as serological testing using both ELISA methodology and lateral flow immunoassay methodology. Although commercial testing systems are becoming available, there will likely be insufficient numbers of such tests due to high demand. Serological testing will be the next testing issue as the COVID\u201019 begins to subside. This will allow immunity testing as well as will allow the parameters of the COVID\u201019 outbreak to be defined. This article is protected by copyright. All rights reserved.", "qid": 8, "docid": "yv5yz261", "rank": 86, "score": 7.897698879241943}, {"content": "Title: Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney. Content: While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches.", "qid": 8, "docid": "8quklm6w", "rank": 87, "score": 7.895100116729736}, {"content": "Title: Advanced Digital Health Technologies for COVID-19 and Future Emergencies Content: Background: Coronavirus disease 2019 (COVID-19) has led to a national health care emergency in the United States and exposed resource shortages, particularly of health care providers trained to provide critical or intensive care. This article describes how digital health technologies are being or could be used for COVID-19 mitigation. It then proposes the National Emergency Tele-Critical Care Network (NETCCN), which would combine digital health technologies to address this and future crises. Methods: Subject matter experts from the Society of Critical Care Medicine and the Telemedicine and Advanced Technology Research Center examined the peer-reviewed literature and science/technology news to see what digital health technologies have already been or could be implemented to (1) support patients while limiting COVID-19 transmission, (2) increase health care providers' capability and capacity, and (3) predict/prevent future outbreaks. Results: Major technologies identified included telemedicine and mobile care (for COVID-19 as well as routine care), tiered telementoring, telecritical care, robotics, and artificial intelligence for monitoring. Several of these could be assimilated to form an interoperable scalable NETCCN. NETCCN would assist health care providers, wherever they are located, by obtaining real-time patient and supplies data and disseminating critical care expertise. NETCCN capabilities should be maintained between disasters and regularly tested to ensure continual readiness. Conclusions: COVID-19 has demonstrated the impact of a large-scale health emergency on the existing infrastructures. Short term, an approach to meeting this challenge is to adopt existing digital health technologies. Long term, developing a NETCCN may ensure that the necessary ecosystem is available to respond to future emergencies.", "qid": 8, "docid": "8wxkrv6h", "rank": 88, "score": 7.892600059509277}, {"content": "Title: Advanced Digital Health Technologies for COVID-19 and Future Emergencies. Content: Background: Coronavirus disease 2019 (COVID-19) has led to a national health care emergency in the United States and exposed resource shortages, particularly of health care providers trained to provide critical or intensive care. This article describes how digital health technologies are being or could be used for COVID-19 mitigation. It then proposes the National Emergency Tele-Critical Care Network (NETCCN), which would combine digital health technologies to address this and future crises. Methods: Subject matter experts from the Society of Critical Care Medicine and the Telemedicine and Advanced Technology Research Center examined the peer-reviewed literature and science/technology news to see what digital health technologies have already been or could be implemented to (1) support patients while limiting COVID-19 transmission, (2) increase health care providers' capability and capacity, and (3) predict/prevent future outbreaks. Results: Major technologies identified included telemedicine and mobile care (for COVID-19 as well as routine care), tiered telementoring, telecritical care, robotics, and artificial intelligence for monitoring. Several of these could be assimilated to form an interoperable scalable NETCCN. NETCCN would assist health care providers, wherever they are located, by obtaining real-time patient and supplies data and disseminating critical care expertise. NETCCN capabilities should be maintained between disasters and regularly tested to ensure continual readiness. Conclusions: COVID-19 has demonstrated the impact of a large-scale health emergency on the existing infrastructures. Short term, an approach to meeting this challenge is to adopt existing digital health technologies. Long term, developing a NETCCN may ensure that the necessary ecosystem is available to respond to future emergencies.", "qid": 8, "docid": "ooh25s0y", "rank": 89, "score": 7.892599105834961}, {"content": "Title: Characterization of the COVID-19 pandemic and the impact of uncertainties, mitigation strategies, and underreporting of cases in South Korea, Italy, and Brazil Content: By April 7th, 2020, the Coronavirus disease 2019 (COVID-19) has infected one and a half million people worldwide, accounting for over 80 thousand of deaths in 209 countries and territories around the world. The new and fast dynamics of the pandemic are challenging the health systems of different countries. In the absence of vaccines or effective treatments, mitigation policies, such as social isolation and lock-down of cities, have been adopted, but the results vary among different countries. Some countries were able to control the disease at the moment, as is the case of South Korea. Others, like Italy, are now experiencing the peak of the pandemic. Finally, countries with emerging economies and social issues, like Brazil, are in the initial phase of the pandemic. In this work, we use mathematical models with time-dependent coefficients, techniques of inverse and forward uncertainty quantification, and sensitivity analysis to characterize essential aspects of the COVID-19 in the three countries mentioned above. The model parameters estimated for South Korea revealed effective social distancing and isolation policies, border control, and a high number in the percentage of reported cases. In contrast, underreporting of cases was estimated to be very high in Brazil and Italy. In addition, the model estimated a poor isolation policy at the moment in Brazil, with a reduction of contact around 40%, whereas Italy and South Korea estimated numbers for contact reduction are at 75% and 90%, respectively. This characterization of the COVID-19, in these different countries under different scenarios and phases of the pandemic, supports the importance of mitigation policies, such as social distancing. In addition, it raises serious concerns for socially and economically fragile countries, where underreporting poses additional challenges to the management of the COVID-19 pandemic by significantly increasing the uncertainties regarding its dynamics.", "qid": 8, "docid": "dwyeggb6", "rank": 90, "score": 7.888700008392334}, {"content": "Title: Scalable and Resilient SARS-CoV2 testing in an Academic Centre Content: The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.", "qid": 8, "docid": "nuw194wf", "rank": 91, "score": 7.8643999099731445}, {"content": "Title: Are co-infections with COVID-19 and Influenza low or underreported? An observational study examining current published literature including three new unpublished cases Content: As the COVID-19 pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020-2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, Texas, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of thirteen patients described therein. Three additional patients were identified from the El Paso, Texas data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome (ARDS). The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens. This article is protected by copyright. All rights reserved.", "qid": 8, "docid": "jrjom1pd", "rank": 92, "score": 7.85260009765625}, {"content": "Title: Are co-infections with COVID-19 and Influenza low or underreported? An observational study examining current published literature including three new unpublished cases. Content: As the COVID-19 pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020-2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, Texas, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of thirteen patients described therein. Three additional patients were identified from the El Paso, Texas data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome (ARDS). The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens. This article is protected by copyright. All rights reserved.", "qid": 8, "docid": "t6datn1z", "rank": 93, "score": 7.852599143981934}, {"content": "Title: Coronavirus 2019 and health systems affected by protracted conflict: The case of Syria Content: INTRODUCTION: Two thirds of countries globally are unprepared to respond to a health emergency as per the International Health Regulations (2005), with conflict-affected countries like Syria being particularly vulnerable. Political influences on outbreak preparedness, response and reporting may also adversely affect control of SARS-CoV-2 in Syria. Syria reported its first case on 22 March 2020; however, concerns were raised that this was delayed and that underreporting continues. DISCUSSION: Syria's conflict has displaced more than half of its pre-war population, leaving 6.7 million people internally displaced. The consequent overcrowding - with insufficient water, sanitation and healthcare (including laboratory capacity) - could lead to conditions that are ideal for spread of SARS-CoV-2 in Syria. Political changes have led to the formation of at least three health systems within Syria's borders, each with its own governance, capacity and planning. This fragmentation, with little interaction between them, could lead to poor resource allocation and adversely affect control. As such, COVID-19 could overwhelm the health systems (particularly intensive care capacity), leading to high deaths across the population, particularly for the most vulnerable such as detainees. CONCLUSIONS: Locally implementable interventions that rapidly build WASH and health system capacity are required across Syria to ensure early detection and management of COVID-19 cases.", "qid": 8, "docid": "qgjr8ldx", "rank": 94, "score": 7.850599765777588}, {"content": "Title: Defining the true impact of coronavirus disease 2019 in the at-risk population of patients with cancer Content: BACKGROUND: In light of the coronavirus disease 2019 (COVID-19) pandemic, cancer centres in the United Kingdom and Europe re-organised their services at an unprecedented pace, and many patients with cancer have had their treatments severely disrupted. Patients with cancer were considered at high risk on sparse evidence, and despite a small number of emerging observational studies, the true incidence and impact of COVID-19 in the \u2018at-risk\u2019 population of patients with cancer is yet to be defined. METHODS: Epidemiological and clinical data were collected prospectively for patients attending the Royal Marsden Hospital and three network hospitals between March 1st and April 30th 2020 that were confirmed to have SARS-CoV2 infection. Significance of clinical and pathological characteristics was assessed using the Fisher's exact test and Wilcoxon rank sum test, whilst univariate and multivariate logistic regression models were used to further assess risk. The number of patients attending in March/April 2020 for face-to-face attendances was also extracted. FINDINGS: During the 2-month study period, 867 of 13,489 (6.4%) patients met the criteria leading to swab testing. Of the total at-risk population, only 113 of 13,489 (0.84%) were swab positive, 101 of 13,489 (0.75%) required hospital admission and 29 of 13,489 (0.21%) died of COVID-19. Of the patients that attended the hospital to receive cytotoxic chemotherapy alone or in combination with other therapy, 59 of 2001 (2.9%) were admitted to the hospital for COVID-19\u2013related issues and 20 of 2001 (1%) died. Of the patients that collected targeted treatments, 16 of 1126 (1.4%) were admitted and 1 of 1126 (0.1%) died. Of the 11 patients that had received radiotherapy, 6 of 1042 (0.6%) required inpatient admission and 2 of 1042 (0.2%) died. INTERPRETATIONS: Administration of systemic anticancer therapy appears to be associated with a modest risk of severe COVID-19 infection. Based on this snapshot taken as the first wave of COVID-19 hit our practice, we conclude that continuation of active cancer treatment, even in the palliative setting, is appropriate.", "qid": 8, "docid": "ngwrfhbl", "rank": 95, "score": 7.832799911499023}, {"content": "Title: Back-projection of COVID-19 diagnosis counts to assess infection incidence and control measures: analysis of Australian data Content: Back-projection is an epidemiological analysis method that was developed to estimate HIV incidence using surveillance data on AIDS diagnoses. It was used extensively during the 1990s for this purpose as well as in other epidemiological contexts. Surveillance data on COVID-19 diagnoses can be analysed by the method of back-projection using information about the probability distribution of the time between infection and diagnosis, which is primarily determined by the incubation period. This paper demonstrates the value of such analyses using daily diagnoses from Australia. It is shown how back-projection can be used to assess the pattern of COVID-19 infection incidence over time and to assess the impact of control measures by investigating their temporal association with changes in incidence patterns. For Australia, these analyses reveal that peak infection incidence coincided with the introduction of border closures and social distancing restrictions, while the introduction of subsequent social distancing measures coincided with a continuing decline in incidence to very low levels. These associations were not directly discernible from the daily diagnosis counts, which continued to increase after the first stage of control measures. It is estimated that a one week delay in peak incidence would have led to a fivefold increase in total infections. Furthermore, at the height of the outbreak, half to three-quarters of all infections remained undiagnosed. Automated data analytics of routinely collected surveillance data are a valuable monitoring tool for the COVID-19 pandemic and may be useful for calibrating transmission dynamics models.", "qid": 8, "docid": "p2e5vdwg", "rank": 96, "score": 7.826300144195557}, {"content": "Title: How many lives can be saved? A global view on the impact of testing, herd immunity and demographics on COVID-19 fatality rates Content: In this work, we assess the global impact of COVID-19 showing how demographic factors, testing policies and herd immunity are key for saving lives. We extend a standard epidemiological SEIR model in order to: (a) identify the role of demographics (population size and population age distribution) on COVID-19 fatality rates; (b) quantify the maximum number of lives that can be saved according to different testing strategies, different levels of herd immunity, and specific population characteristics; and (d) infer from the observed case fatality rates (CFR) what the true fatality rate might be. Different from previous SEIR model extensions, we implement a Bayesian Melding method in our calibration strategy which enables us to account for data limitation on the total number of deaths. We derive a distribution of the set of parameters that best replicate the observed evolution of deaths by using information from both the model and the data.", "qid": 8, "docid": "2epo3a4r", "rank": 97, "score": 7.818600177764893}, {"content": "Title: Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results Content: Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/.", "qid": 8, "docid": "kjovtgua", "rank": 98, "score": 7.812600135803223}, {"content": "Title: Clinical and transmission dynamics characteristics of 406 children with coronavirus disease 2019 in China: A review Content: OBJECTIVE: Chinese pediatricians are working on the front line to fight COVID-19. They have published a great amount of first-hand clinical data. Collecting their data and forming a large sample for analysis is more conducive to the recognition, prevention and treatment of coronavirus disease 2019 in children. The epidemic prevention and control experience of Chinese pediatricians should be shared with the world. METHODS: By searching Chinese and English literature, the data of 406 children with COVID-19 in China were analyzed. RESULTS: It was found that the clustered incidence of children's families is a dynamic transmission feature; the incidence is low; asymptomatic infections and mild cases account for 44.8%, with only 7 cases of critical illness; laboratory examination of lymphocyte counts is not reduced, as it is for adults; chest CT findings are less severe than those for adults. These presentations are the clinical features of COVID-19 in children. Only 55 of the 406 cases were tested by anal swab for virus nucleic acid, 45 of which were positive, accounting for 81.8% of stool samples. CONCLUSION: There are more children than adults with asymptomatic infections, milder conditions, faster recovery, and a better prognosis. Some concealed morbidity characteristics also bring difficulties to the early identification, prevention and control of COVID-19. COVID-19 screening is needed in the pediatric fever clinic, and respiratory and digestive tract nucleic acid tests should be performed. Efforts should be made to prevent children from becoming a hidden source of transmission in kindergartens, schools or families. Furthermore, China's experience in treating COVID-19 in children has led to faster recovery of sick children.", "qid": 8, "docid": "bih9t439", "rank": 99, "score": 7.7692999839782715}, {"content": "Title: Clinical and Transmission Dynamics Characteristics of 406 Children with Coronavirus Disease 2019 in China: A Review Content: Abstract Objective Chinese pediatricians are working on the front line to fight COVID-19. They have published a great amount of first-hand clinical data. Collecting their data and forming a large sample for analysis is more conducive to the recognition, prevention and treatment of coronavirus disease 2019 in children. The epidemic prevention and control experience of Chinese pediatricians should be shared with the world. Methods By searching Chinese and English literature, the data of 406 children with COVID-19 in China were analyzed. Results It was found that the clustered incidence of children's families is a dynamic transmission feature; the incidence is low; asymptomatic infections and mild cases account for 44.8%, with only 7 cases of critical illness; laboratory examination of lymphocyte counts is not reduced, as it is for adults; chest CT findings are less severe than those for adults. These presentations are the clinical features of COVID-19 in children. Only 55 of the 406 cases were tested by anal swab for virus nucleic acid, 45 of which were positive, accounting for 81.8% of stool samples. Conclusion There are more children than adults with asymptomatic infections, milder conditions, faster recovery, and a better prognosis. Some concealed morbidity characteristics also bring difficulties to the early identification, prevention and control of COVID-19. COVID-19 screening is needed in the pediatric fever clinic, and respiratory and digestive tract nucleic acid tests should be performed. Efforts should be made to prevent children from becoming a hidden source of transmission in kindergartens, schools or families. Furthermore, China's experience in treating COVID-19 in children has led to faster recovery of sick children.", "qid": 8, "docid": "pqg0g1nx", "rank": 100, "score": 7.769299030303955}]}
{"query": "how has COVID-19 affected Canada", "hits": [{"content": "Title: Has the COVID-19 Pandemic Affected MPs\u2019 Representational Activities? Content: The COVID-19 pandemic has necessarily affected the operation of Canada's Parliament and, thus, the activities of Members of Parliament (MPs) (Malloy, 2020; Rayment and VandenBeukel, 2020). Here, we explore how the pandemic has affected the representational activities of individual MPs.", "qid": 9, "docid": "u8hogdyf", "rank": 1, "score": 9.695099830627441}, {"content": "Title: Disruption to surgical training during Covid-19 in the United States, United Kingdom, Canada and Australasia: a rapid review of impact and mitigation efforts Content: The global Covid-19 pandemic has the potential to lead to significant training disruptions affecting surgical residents across all specialties. There has been lively social media discussion about the impact of cancelled training activities under the twitter hashtag #NoTrainingTodayNoSurgeonsTomorrow. We present a rapid scoping review synthesising the current evidence of pandemic-related impact on surgical training in the United States, United Kingdom, Canada, Australia and New Zealand. We describe and compare strategies that have been put in place to mitigate disruption, and reflect on how the challenges of the pandemic may present the opportunity to improve on how we select, assess and train surgeons in the future.", "qid": 9, "docid": "zzvmj5qy", "rank": 2, "score": 9.623299598693848}, {"content": "Title: COVID-19, extractive industries, and indigenous communities in Canada: Notes towards a political economy research agenda Content: As the economic ramifications of the COVID-19 pandemic continue to unfold, it is becoming increasingly apparent that this crisis will have significant and lasting implications for the relationship between extractive industries and Indigenous communities. Using a case study from Canada, this paper examines how the political dynamics of industry-Indigenous relations have changed and speculates about how these dynamics might continue to change in the future. The economic crisis has already intensified political conflicts and struggles between Indigenous peoples and mining, oil, and gas companies. We identify and discuss four points of conflict between Indigenous communities and extractive industries that have become more acute as a result of the current economic crisis. It is important for researchers to pay close attention to how these conflicts are affected by the pandemic, in order to help Indigenous communities develop strategies to cope with changes in industry-Indigenous relations.", "qid": 9, "docid": "rzwcfv3b", "rank": 3, "score": 9.443900108337402}, {"content": "Title: Severe acute respiratory syndrome and its effects on health care: how Canada has dealt with this ordeal. Content: The global epidemic of severe acute respiratory syndrome (SARS) indirectly has affected all health care facilities in affected nations and has unaffected nations on alert. Health care practitioners need to be aware of infection control measures to prevent the spread of SARS. This article looks at this new disease and how it has affected the delivery of health care in Canada.", "qid": 9, "docid": "xm9y4ovl", "rank": 4, "score": 9.176799774169922}, {"content": "Title: An Evaluation of Neurosurgical Resident Education and Sentiment During the Coronavirus Disease 2019 Pandemic: A North American Survey Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous impact on the healthcare system. Owing to restrictions in elective surgery and social distancing guidelines, the training curriculum for neurosurgical trainees has been rapidly evolving. This evolution could have significant long-term effects on the training of neurosurgery residents. The objective of the present study was to assess the effects of COVID-19 on neurosurgical training programs and residents. METHODS: A survey consisting of 31 questions assessing changes to resident clinical and educational workload and their sentiment regarding how these changes might affect their careers was distributed electronically to neurosurgery residents in the United States and Canada. RESULTS: The survey respondents were from 29 states and Canada and were relatively evenly spread across all levels of residency. Nearly 82% reported that the inpatient and outpatient volumes had been either greatly (44.0%) or moderately (37.8%) reduced. Greater than 91% reported that their work responsibilities or access to the hospital had been reduced, with a significant reduction in work hours and a significant increase in resident didactics (P < 0.001). Senior residents expressed concern about their educational experience and their future career prospects as a result of the pandemic. CONCLUSION: Universally, residents have experienced reduced work hours and a reduction in their operative case volumes. Programs have adapted by increasing didactic time and using electronic platforms. It is quite possible that this remarkable period will prompt a critical reappraisal of the pre-COVID-19 adequacy of educational content in our training programs and that the enhanced educational efforts driven by this pandemic could be lasting.", "qid": 9, "docid": "vmy1zk8e", "rank": 5, "score": 8.380900382995605}, {"content": "Title: An Evaluation of Neurosurgical Resident Education and Sentiment During the COVID-19 Pandemic: A North American Survey Content: ABSTRACT Background The COVID-19 pandemic has had a tremendous impact on the healthcare system. Due to restrictions in elective surgery and social distancing guidelines, the training curriculum for neurosurgical trainees is rapidly evolving. This evolution may have significant long-term effects on the training of neurosurgery residents. Objective To assess the impact of COVID-19 on neurosurgical training programs and residents. Methods A survey consisting of thirty-one questions assessing changes to resident clinical and educational workload and their sentiment on how these changes may affect their careers was distributed electronically to neurosurgery residents in the United States and Canada. Results The survey respondents were spread over 29 states and Canada and were relatively evenly spread across all levels of residency. Nearly 82% reported that the inpatient and outpatient volumes were either greatly (44.0%) or moderately (37.8%) reduced. Greater than 91% reported that their work responsibilities or access to the hospital had been reduced with a significant reduction in work hours and a significant increase in resident didactics (p <.001). Senior residents expressed concern about their educational experience as well as their future career prospects as a result of the pandemic. Conclusion Universally, residents have experienced reduced work hours and reduction in their operative case volumes. Programs have adapted by increasing didactic time and using electronic platforms. It is quite possible that this remarkable time period will prompt a critical re-appraisal of the pre-COVID-19 adequacy of educational content in our training programs, and that enhanced educational efforts driven by this pandemic may be lasting.", "qid": 9, "docid": "0p192lmv", "rank": 6, "score": 8.258099555969238}, {"content": "Title: Canada\u2019s role in strengthening global health security during the COVID-19 pandemic Content: The world is confronted by the current pandemic of Corona Virus Disease (COVID-19), which is a wake-up call for all nations irrespective of their development status or geographical location. Since the start of the century we have seen five big infectious outbreaks which proved that epidemics are no more regarded as historic and geographically confined threats. The Canadian government underlined that these infectious disease outbreaks are threats to global health security and disrupt societal wellbeing and development. In this context, the Public Health Agency of Canada is proactive and has shown its preparedness for outbreaks of emerging and epidemic-prone diseases, and in dealing with these pathogens. Even before the declaration of pandemic, Canada has proved its global health leadership by ensuring collective action and multisectoral coordination which still remains a serious challenge especially for low and middle- income countries with existing poor health systems. In this article we discuss how Canada is addressing the global challenges posed by the COVID-19 pandemic through its leadership and practice of global health diplomacy.", "qid": 9, "docid": "qy66ih4m", "rank": 7, "score": 8.192700386047363}, {"content": "Title: Optimizing Access to Heart Failure Care in Canada During the COVID-19 Pandemic Content: The traditional model of heart failure (HF) care in Canada, which relies upon a multidisciplinary team and clinic-based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the health care workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization. As such, we must quickly pivot to the adoption and application of novel technologies and revise usual care models, processes, and workflow. The unprecedented COVID-19 crisis has delivered the Canadian HF community a burning platform for the design and implementation of innovative approaches to support the vulnerable population we serve; born out of necessity, we now have the opportunity to explore innovative approaches that might inform the future of HF care delivery in Canada. Herein, we provide perspectives from leadership within the Canadian Heart Failure Society on how to optimize HF care during the COVID-19 pandemic.", "qid": 9, "docid": "23pm2kjw", "rank": 8, "score": 7.993599891662598}, {"content": "Title: Optimizing Access to Heart Failure Care in Canada during the COVID-19 Pandemic Content: The traditional model of heart failure (HF) care in Canada, which relies upon a multi-disciplinary team and clinic based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the healthcare workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization. As such, we must quickly pivot to the adoption and application of novel technologies and revise usual care models, processes, and workflow. The unprecedented COVID-19 crisis has delivered the Canadian HF community a burning platform for the design and implementation of innovative approaches to support the vulnerable population we serve; born out of necessity, we now have the opportunity to explore innovative approaches that may inform the future of HF care delivery in Canada. Herein, we provide perspectives from leadership within the Canadian Heart Failure Society (CHFS) on how to optimize HF care during the COVID-19 pandemic.", "qid": 9, "docid": "vn9ba1ku", "rank": 9, "score": 7.993598937988281}, {"content": "Title: Trial by Zoom? The Response to COVID-19 by Canada's Courts Content: COVID-19 has made videoconferencing a regular occurrence in the lives of Canadians. Videoconferencing is being used to maintain social ties, run business meetings\u2014and to uphold responsible government. On April 28, 2020, Members of the House of Commons sat virtually using Zoom. The virtual sitting was the first of what will become a stand-in for regular proceedings, allowing the Members to fulfill some of their parliamentary duties while complying with physical distancing (see Malloy, 2020). As the legislative and executive branches look to digital technology to allow the business of government to continue, what about the judicial branch of Canada's government? Courts are an essential service. This is best articulated by the Chief Justice of Nova Scotia: \u201cThe fact is, the Courts cannot close. As the third branch of government, an independent judiciary is vital for our Canadian democracy to function. It is never more important than in times of crisis\u201d (Wood, 2020). In this analysis, we seek to understand how courts have responded to COVID-19 and the challenges of physical distancing through the use of digital technologies. This is accomplished through a systematic review of COVID-19 statements and directives issued from all levels of court across Canada. We briefly compare Canada to the United States, a jurisdiction that demonstrates greater openness to technology.", "qid": 9, "docid": "qy9ttbkx", "rank": 10, "score": 7.957799911499023}, {"content": "Title: Assessing the burden of COVID-19 in Canada Content: Background: The burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. Methods: Using newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. Results: Quebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. Interpretation: Although health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.", "qid": 9, "docid": "54obt430", "rank": 11, "score": 7.915900230407715}, {"content": "Title: Chasing the origin of SARS-CoV-2 in Canada\u2019s COVID-19 cases: A genomics study Content: The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.", "qid": 9, "docid": "8gtnbm1c", "rank": 12, "score": 7.847799777984619}, {"content": "Title: Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons Content: On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic.1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries.1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement.2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19-related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories.3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences.", "qid": 9, "docid": "mzaxgbtc", "rank": 13, "score": 7.773399829864502}, {"content": "Title: COVID-19 in Canada: Predictions for the future and control lessons from Asia Content: COVID-19 has spread with unequal efficiency in various parts of the world. In several European countries including Italy, the increase in the number of COVID-19 cases has followed a consistent, exponential pattern of spread. However, some countries, notably Taiwan and Hong Kong, have achieved a different outcome and have managed to bring the COVID-19 outbreak in their countries rapidly under control, without entering the exponential pattern and with very few cases. They have used several different approaches to COVID-19 outbreak control, including the innovative use of smartphone technology and the widespread use of surgical face masks. We show through our models, that Canada has followed the same, consistent COVID-19 exponential growth pattern that is seen in Italy. Both nationally and in its most heavily affected provinces, there is exponential growth of COVID-19 cases, making it possible to make predictions for the future, if no further interventions are made in public health policy. In particular, we argue for the urgent introduction of surgical face masks in health care and other settings and the harnessing of the power of smartphone technology on a national scale.", "qid": 9, "docid": "ieobv7q8", "rank": 14, "score": 7.75439977645874}, {"content": "Title: Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons Content: Abstract On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic. 1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries. 1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement. 2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19\u2013related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories. 3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences. A visual abstract of the main principles underlying our recommended approach is provided in Figure 1.", "qid": 9, "docid": "n8omnki4", "rank": 15, "score": 7.668300151824951}, {"content": "Title: Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America Content: BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a \u201cstay-at-home\u201d order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.", "qid": 9, "docid": "2pfeogz0", "rank": 16, "score": 7.593699932098389}, {"content": "Title: Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America Content: BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a \"stay-at-home\" order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.", "qid": 9, "docid": "sdrst5nm", "rank": 17, "score": 7.593698978424072}, {"content": "Title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report. Content: Background The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were\u25a0 cancer prognosis and anticipated benefit from treatment,\u25a0 risk of treatment toxicity during scarce health care access, and\u25a0 patient risk of contracting covid-19. Conclusions This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "qid": 9, "docid": "ux0kjt9l", "rank": 18, "score": 7.405700206756592}, {"content": "Title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report Content: Background: The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods: An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results: More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were\u00e2\u0096 cancer prognosis and anticipated benefit from treatment,\u00e2\u0096 risk of treatment toxicity during scarce health care access, and\u00e2\u0096 patient risk of contracting covid-19. Conclusions: This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "qid": 9, "docid": "y8ntig41", "rank": 19, "score": 7.405699253082275}, {"content": "Title: Exploratory Analysis of COVID-19 Related Tweets in North America to Inform Public Health Institutes Content: Social media is a rich source where we can learn about people's reactions to social issues. As COVID-19 has significantly impacted on people's lives, it is essential to capture how people react to public health interventions and understand their concerns. In this paper, we aim to investigate people's reactions and concerns about COVID-19 in North America, especially focusing on Canada. We analyze COVID-19 related tweets using topic modeling and aspect-based sentiment analysis, and interpret the results with public health experts. We compare timeline of topics discussed with timing of implementation of public health interventions for COVID-19. We also examine people's sentiment about COVID-19 related issues. We discuss how the results can be helpful for public health agencies when designing a policy for new interventions. Our work shows how Natural Language Processing (NLP) techniques could be applied to public health questions with domain expert involvement.", "qid": 9, "docid": "yuv2ki4o", "rank": 20, "score": 7.3780999183654785}, {"content": "Title: Vulnerability of Aboriginal health systems in Canada to climate change Content: Abstract Climate change has been identified as potentially the biggest health threat of the 21st century. Canada in general has a well developed public health system and low burden of health which will moderate vulnerability. However, there is significant heterogeneity in health outcomes, and health inequality is particularly pronounced among Aboriginal Canadians. Intervention is needed to prevent, prepare for, and manage climate change effects on Aboriginal health but is constrained by a limited understanding of vulnerability and its determinants. Despite limited research on climate change and Aboriginal health, however, there is a well established literature on Aboriginal health outcomes, determinants, and trends in Canada; characteristics that will determine vulnerability to climate change. In this paper we systematically review this literature, using a vulnerability framework to identify the broad level factors constraining adaptive capacity and increasing sensitivity to climate change. Determinants identified include: poverty, technological capacity constraints, socio-political values and inequality, institutional capacity challenges, and information deficit. The magnitude and nature of these determinants will be distributed unevenly within and between Aboriginal populations necessitating place-based and regional level studies to examine how these broad factors will affect vulnerability at lower levels. The study also supports the need for collaboration across all sectors and levels of government, open and meaningful dialogue between policy makers, scientists, health professionals, and Aboriginal communities, and capacity building at a local level, to plan for climate change. Ultimately, however, efforts to reduce the vulnerability of Aboriginal Canadians to climate change and intervene to prevent, reduce, and manage climate-sensitive health outcomes, will fail unless the broader determinants of socio-economic and health inequality are addressed.", "qid": 9, "docid": "5m1ch7ls", "rank": 21, "score": 7.256899833679199}, {"content": "Title: Comparing \u201cinsider\u201d and \u201coutsider\u201d news coverage of the 2014 Ebola outbreak Content: OBJECTIVES: Information provided by news media during an infectious disease outbreak can affect the actions taken to safeguard public health. There has been little evaluation of how the content of news published during an outbreak varies by location of the news outlet. This study analyzes coverage of the 2014 Ebola outbreak by one news outlet operating within a country affected by the outbreak and one country not directly affected. METHODS: A qualitative content analysis was conducted of articles published in two national news outlets, The Globe and Mail (Canada) and the Vanguard (Nigeria), between January 1 and December 31, 2014. Articles available through LexisNexis Academic were sorted by date and sampled using a stratified sampling method (The Globe and Mail n = 100; Vanguard n = 105). A coding scheme was developed and modified to incorporate emerging themes until saturation was achieved. RESULTS: There were substantial differences in outbreak coverage in terms of the topic and content of the articles, as well as the sources consulted. The Globe and Mail framed the outbreak in terms of national security and national interests, as well as presenting it as an international humanitarian crisis. In contrast, the Vanguard framed the outbreak almost exclusively in terms of public health. CONCLUSION: Our findings highlight how different geographic contexts can shape reporting on the same event. Further research is required to investigate how the political, social or economic situations of a country shape its news media, potentially influencing actions taken to control disease outbreaks.", "qid": 9, "docid": "74qmy02h", "rank": 22, "score": 7.229300022125244}, {"content": "Title: Real-time forecasts and risk assessment of novel coronavirus (COVID-19) cases: A data-driven analysis Content: The coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern affecting 201 countries and territories around the globe. As of April 4, 2020, it has caused a pandemic outbreak with more than 11,16,643 confirmed infections and more than 59,170 reported deaths worldwide. The main focus of this paper is two-fold: (a) generating short term (real-time) forecasts of the future COVID-19 cases for multiple countries; (b) risk assessment (in terms of case fatality rate) of the novel COVID-19 for some profoundly affected countries by finding various important demographic characteristics of the countries along with some disease characteristics. To solve the first problem, we presented a hybrid approach based on autoregressive integrated moving average model and Wavelet-based forecasting model that can generate short-term (ten days ahead) forecasts of the number of daily confirmed cases for Canada, France, India, South Korea, and the UK. The predictions of the future outbreak for different countries will be useful for the effective allocation of health care resources and will act as an early-warning system for government policymakers. In the second problem, we applied an optimal regression tree algorithm to find essential causal variables that significantly affect the case fatality rates for different countries. This data-driven analysis will necessarily provide deep insights into the study of early risk assessments for 50 immensely affected countries.", "qid": 9, "docid": "ba6mdgq3", "rank": 23, "score": 7.198500156402588}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: The novel coronavirus 2019 disease (COVID-19) pandemic has placed intense pressure on health care organizations around the world. Among other concerns, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with preexisting cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent and, in some cases, prolonged rehabilitation needs after acute hospitalization. This report describes the current status of post-discharge cardiac care in Canada and provides suggestions regarding steps that policymakers and health care organizations can take to prepare for the COVID-19 pandemic.", "qid": 9, "docid": "8508n0ex", "rank": 24, "score": 7.084099769592285}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: Abstract The novel coronavirus 2019 (COVID-19) pandemic has placed intense pressure on healthcare organizations around the world. Amongst others, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with pre-existing cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent, and in some cases, prolonged rehabilitation needs following acute hospitalization. This manuscript describes the current status of post-discharge cardiac care in Canada and provides suggestions with regards to steps that policymakers and healthcare organizations can take to prepare for the COVID-19 pandemic.", "qid": 9, "docid": "8obqdbh9", "rank": 25, "score": 7.084098815917969}, {"content": "Title: Canada needs to rapidly escalate public health interventions for its COVID-19 mitigation strategies Content: BACKGROUND: After the declaration of COVID-19 pandemic on March 11th(,) 2020, local transmission chains starting in different countries including Canada are forcing governments to take decisions on public health interventions to mitigate the spread of the epidemic. METHODS: We conduct data-driven and model-free estimations for the growth rates of the COVID-19 epidemics in Italy and Canada, by fitting an exponential curve to the daily reported cases. We use these estimates to predict epidemic trends in Canada under different scenarios of public health interventions. RESULTS: In Italy, the initial growth rate (0.22) has reduced to 0.1 two weeks after the lockdown of the country on March 8th(,) 2020. This corresponds to an increase of the doubling time from about 3.15 to almost 7 days. In comparison, the growth rate in Canada has increased from 0.13 between March 1st and 13th, to 0.25 between March 13th to 22nd. This current growth rate corresponds to a doubling time of 2.7 days, and therefore, unless further public health interventions are escalated in Canada, we project 15,000 cases by March 31st. However, the case number may be reduced to 4000 if escalated public health interventions could instantly reduce the growth rate to 0.1, the same level achieved in Italy. INTERPRETATION: Prompt and farsighted interventions are critical to counteract the very rapid initial growth of the COVID-19 epidemic in Canada. Mitigation plans must take into account the delayed effect of interventions by up to 2-weeks and the short doubling time of 3\u20134 days.", "qid": 9, "docid": "vwwt70mo", "rank": 26, "score": 6.991000175476074}, {"content": "Title: Pandemic Parliaments: Canadian Legislatures in a Time of Crisis Content: Canadian legislatures\u2019 responses to the COVID-19 pandemic have raised questions about whether and how parliaments should continue to meet during the pandemic (Reid, 2020; Thomas, 2020a). The purpose of this research note is twofold: (1) to document how Canadian legislatures have changed in response to the COVID-19 pandemic and (2) to assess the effect of these responses on legislatures\u2019 ability to fulfill their core functions. Through an analysis of parliamentary records from all elected federal, provincial and territorial legislatures in Canada, we find that the role of parliaments as sites of citizen representation has suffered the most, whereas the scrutinizing and legislative functions of parliaments have tended to be preserved, albeit in a significantly truncated form. We argue that patterns in legislatures' varied responses to the pandemic reveal which aspects of parliamentary functioning these bodies de facto prioritize and which are at risk of being eroded.", "qid": 9, "docid": "hxn46xnn", "rank": 27, "score": 6.979400157928467}, {"content": "Title: How Has COVID-19 Affected Our Orthopedic Implant Industry Partners? Implications for the Surgeon-Industry Relationship in 2020 and Beyond Content: BACKGROUND: The COVID-19 pandemic has had far-reaching societal and financial consequences. The purpose of this study was to evaluate how COVID-19 has affected AAHKS industry partners and the surgeon-industry relationship, emphasizing education, resource allocation, and strategic direction for the 2nd half of 2020. METHODS: AAHKS industry partners were contacted to participate in a blinded survey and optional interview with the AAHKS Industry Relations Committee. Based on the results, a group of AAHKS member surgeons with disparate practice types were asked to postulate on how the COVID-19 pandemic has and will affect their practice and relationship with Industry. RESULTS: AAHKS industry partner responses indicated decreased resource allocation for regional, \u201cother national,\u201d and AAHKS annual meetings (67%, 55%, and 30%, respectively). Web-based educational content was expected to increase in 2020 and will likely remain a point of emphasis in 2021 (100% and 70% of responders). For Q3/Q4 2020, a significant emphasis was placed on site of service/outpatient TJA and COVID-19-related safety measures (70% and 90% of responders), as well as increased availability of instrumentation and implants (40% and 60%, respectively). CONCLUSION: The COVID-19 pandemic has altered the orthopedic landscape for the foreseeable future. Survey responses by AAHKS industry partners demonstrate a continued commitment to surgeon education with and increasing shift to a web-based platform. Increased resource allocation for outpatient TJA and COVID-19-related safety measures were significant. Articulating optimal mechanisms to aid industry in supporting surgeons with different practice models to meet demand during the second half of fiscal year 2020 will be critical.", "qid": 9, "docid": "4bncbqsb", "rank": 28, "score": 6.91510009765625}, {"content": "Title: How Has COVID-19 Affected Our Orthopedic Implant Industry Partners? Implications for the Surgeon-Industry Relationship in 2020 and Beyond Content: BACKGROUND: The COVID-19 pandemic has had far-reaching societal and financial consequences. The purpose of this study was to evaluate how COVID-19 has affected AAHKS industry partners and the surgeon-industry relationship, emphasizing education, resource allocation, and strategic direction for the second half of 2020. METHODS: AAHKS industry partners were contacted to participate in a blinded survey and optional interview with the AAHKS Industry Relations Committee. Based on the results, a group of AAHKS member surgeons with disparate practice types were asked to postulate on how the COVID-19 pandemic has and will affect their practice and relationship with Industry. RESULTS: AAHKS industry partner responses indicated decreased resource allocation for regional, \"other national,\" and AAHKS annual meetings (67%, 55%, and 30%, respectively). Web-based educational content was expected to increase in 2020 and will likely remain a point of emphasis in 2021 (100% and 70% of responders). For Q3/Q4 2020, a significant emphasis was placed on site of service/outpatient TJA and COVID-19-related safety measures (70% and 90% of responders), as well as increased availability of instrumentation and implants (40% and 60%, respectively). CONCLUSION: The COVID-19 pandemic has altered the orthopedic landscape for the foreseeable future. Survey responses by AAHKS industry partners demonstrate a continued commitment to surgeon education with an increasing shift to a web-based platform. Increased resource allocation for outpatient TJA and COVID-19-related safety measures were significant. Articulating optimal mechanisms to aid industry in supporting surgeons with different practice models to meet demand during the second half of fiscal year 2020 will be critical.", "qid": 9, "docid": "8pw5r3px", "rank": 29, "score": 6.915099143981934}, {"content": "Title: \"The storm has arrived\": the impact of SARS-CoV-2 on medical students Content: In a few weeks, the global community has witnessed, and for some of us experienced first-hand, the human costs of the COVID-19 pandemic. There is incredible variability in how countries are choosing to thwart the disease's outbreak, sparking intense discussions around what it means to teach and learn in the era of COVID-19, and more specifically, the role medical students play in the midst of the pandemic. A multi-national and multi-institutional group made up of a dedicated medical student from Austria, passionate clinicians and educators from Switzerland, and a PhD scientist involved in Medical Education from Canada, have assembled to summarize the ingenious ways medical students around the world are contributing to emergency efforts. They argue that such efforts change COVID-19 from a \"disruption\" to medical students learning to something more tangible, more important, allowing students to become stakeholders in the expansion and delivery of healthcare.", "qid": 9, "docid": "fjf3dm4y", "rank": 30, "score": 6.914899826049805}, {"content": "Title: \u201cThe storm has arrived\u201d: the impact of SARS-CoV-2 on medical students Content: In a few weeks, the global community has witnessed, and for some of us experienced first-hand, the human costs of the COVID-19 pandemic. There is incredible variability in how countries are choosing to thwart the disease\u2019s outbreak, sparking intense discussions around what it means to teach and learn in the era of COVID-19, and more specifically, the role medical students play in the midst of the pandemic. A multi-national and multi-institutional group made up of a dedicated medical student from Austria, passionate clinicians and educators from Switzerland, and a PhD scientist involved in Medical Education from Canada, have assembled to summarize the ingenious ways medical students around the world are contributing to emergency efforts. They argue that such efforts change COVID-19 from a \u201cdisruption\u201d to medical students learning to something more tangible, more important, allowing students to become stakeholders in the expansion and delivery of healthcare.", "qid": 9, "docid": "pkniwunl", "rank": 31, "score": 6.914898872375488}, {"content": "Title: The impact of COVID-19 on fieldwork efforts and planning in pairfam and FReDA-GGS Content: The worldwide spread of the COVID-19 pandemic has disrupted the fieldwork of surveys. The data collection efforts via the face-to-face mode have been affected especially, including the ongoing surveys that were in the field during the COVID-19 outbreak and the planned surveys scheduled for fieldwork later in 2020. We provide an account of how COVID-19 has impacted two family studies in Germany: \u201cThe German Family Panel\u201d (pairfam) and the \u201cGenerations and Gender Survey\u201d (GGS) both of which will be part of the \u201cFamily Research and Demographic Analysis\u201d (FReDA) infrastructure. Based on pairfam, we illustrate the effects of the pandemic on ongoing data collection and the measures taken to proceed with fieldwork, and we report on a special COVID-19 survey. Based on FReDA-GGS, we outline how COVID-19 has affected our planned survey schedules, what future challenges are expected when fieldwork becomes possible again, and how we have adapted our plans accordingly.", "qid": 9, "docid": "kv16lxve", "rank": 32, "score": 6.90369987487793}, {"content": "Title: How Has COVID-19 Affected the Costs of the Surgical Fellowship Interview Process? Content: OBJECTIVE: To evaluate the effect of COVID-19 on the costs of the surgical fellowship interview process. DESIGN: A literature review of the historical costs of surgical fellowship interviews and a summary of how the shift to virtual interviews has unintended positive and negative effects on costs for applicants and training programs. RESULTS: Transitioning fellowship interviews to virtual platforms affects expenditures of finances and time. Each fellowship candidate saves close to $6,000 in interview travel expenses. Applicants require less time off from their residency programs during this critical time of need for frontline healthcare workers. However, applicants miss some of the live aspects of interviewing, and training programs invest more effort upfront altering their interviews to virtual formats. CONCLUSIONS: The COVID-19 public health crisis has had a significant impact on surgical education, including how selection is conducted. Virtual recruitment has the potential for cost savings but should continue to be refined. This is an opportune time to innovate and rethink how to recruit prospective surgical residency and fellowship candidates during the current and forthcoming interview seasons.", "qid": 9, "docid": "wizfsv6x", "rank": 33, "score": 6.846700191497803}, {"content": "Title: Surgical wait list management in Canada during a pandemic: many challenges ahead Content: Summary: The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on waits for elective operations, with tens of thousands of scheduled surgeries being cancelled or postponed across Canada. Provincial governments will likely not only reopen elective surgical capacity when it is deemed safe, but also target new funding to address the backlog of cases. There is a dearth of research on whether the provinces' approaches to managing wait lists are equitable from a patients' needs perspective or if they are associated with patients' perception of outcomes. The surgical cost models used in the past won't be useful to governments and hospital managers. New models based on hospitals' marginal costs, associated with running on weekends or off-hours and social distancing parameters, will be needed. Surgeon input, collaboration and leadership during the strategy development, implementation and management of surgical wait lists postpandemic will be imperative, as these decisions will significantly affect the health and lives of many Canadians.", "qid": 9, "docid": "483t4low", "rank": 34, "score": 6.838600158691406}, {"content": "Title: Surgical wait list management in Canada during a pandemic: many challenges ahead. Content: Summary The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on waits for elective operations, with tens of thousands of scheduled surgeries being cancelled or postponed across Canada. Provincial governments will likely not only reopen elective surgical capacity when it is deemed safe, but also target new funding to address the backlog of cases. There is a dearth of research on whether the provinces' approaches to managing wait lists are equitable from a patients' needs perspective or if they are associated with patients' perception of outcomes. The surgical cost models used in the past won't be useful to governments and hospital managers. New models based on hospitals' marginal costs, associated with running on weekends or off-hours and social distancing parameters, will be needed. Surgeon input, collaboration and leadership during the strategy development, implementation and management of surgical wait lists postpandemic will be imperative, as these decisions will significantly affect the health and lives of many Canadians.", "qid": 9, "docid": "6cipl2v3", "rank": 35, "score": 6.83859920501709}, {"content": "Title: Novel Coronavirus, Old Partisanship: COVID-19 Attitudes and Behaviours in the United States and Canada Content: The novel coronavirus reached the United States and Canada almost at the same time. The first reported American case was January 20, 2020, and in Canada it was January 15, 2020 (Canada, 2020; Holshue et al., 2020). Yet, the response to this crisis has been different in the two countries. In the US, President Donald Trump, prominent Republicans, and conservative media initially dismissed the dangers of COVID-19 (Stecula, 2020). The pandemic became politicized from the early days, and even though Trump and Republicans have walked back many of their initial claims, there continue to be media reports of partisan differences in public opinion shaped by that early response. At the same time, the response in Canada has been mostly characterized by across-the-board partisan consensus among political elites (Merkley et al., 2020).", "qid": 9, "docid": "4v3d86h3", "rank": 36, "score": 6.831099987030029}, {"content": "Title: Mathematical modelling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada. Content: BACKGROUND Physical-distancing interventions are being used in Canada to slow the spread of severe acute respiratory syndrome coronavirus 2, but it is not clear how effective they will be. We evaluated how different nonpharmaceutical interventions could be used to control the coronavirus disease 2019 (COVID-19) pandemic and reduce the burden on the health care system. METHODS We used an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada. We compared a base case with limited testing, isolation and quarantine to scenarios with the following: enhanced case finding, restrictive physical-distancing measures, or a combination of enhanced case finding and less restrictive physical distancing. Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected occupancy of intensive care unit (ICU) beds. We present medians and credible intervals from 100 replicates per scenario using a 2-year time horizon. RESULTS We estimated that 56% (95% credible interval 42%-63%) of the Ontario population would be infected over the course of the epidemic in the base case. At the epidemic peak, we projected 107 000 (95% credible interval 60 760-149 000) cases in hospital (non-ICU) and 55 500 (95% credible interval 32 700-75 200) cases in ICU. For fixed-duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive physical distancing estimated to have the greatest effect. Longer duration interventions were more effective. Dynamic interventions were projected to reduce the proportion of the population infected at the end of the 2-year period and could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity. INTERPRETATION Without substantial physical distancing or a combination of moderate physical distancing with enhanced case finding, we project that ICU resources would be overwhelmed. Dynamic physical distancing could maintain health-system capacity and also allow periodic psychological andeconomic respite for populations.", "qid": 9, "docid": "j8x384vp", "rank": 37, "score": 6.790800094604492}, {"content": "Title: Mathematical modelling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada Content: BACKGROUND: Physical-distancing interventions are being used in Canada to slow the spread of severe acute respiratory syndrome coronavirus 2, but it is not clear how effective they will be. We evaluated how different nonpharmaceutical interventions could be used to control the coronavirus disease 2019 (COVID-19) pandemic and reduce the burden on the health care system. METHODS: We used an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada. We compared a base case with limited testing, isolation and quarantine to scenarios with the following: enhanced case finding, restrictive physical-distancing measures, or a combination of enhanced case finding and less restrictive physical distancing. Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected occupancy of intensive care unit (ICU) beds. We present medians and credible intervals from 100 replicates per scenario using a 2-year time horizon. RESULTS: We estimated that 56% (95% credible interval 42%-63%) of the Ontario population would be infected over the course of the epidemic in the base case. At the epidemic peak, we projected 107 000 (95% credible interval 60 760-149 000) cases in hospital (non-ICU) and 55 500 (95% credible interval 32 700-75 200) cases in ICU. For fixed-duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive physical distancing estimated to have the greatest effect. Longer duration interventions were more effective. Dynamic interventions were projected to reduce the proportion of the population infected at the end of the 2-year period and could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity. INTERPRETATION: Without substantial physical distancing or a combination of moderate physical distancing with enhanced case finding, we project that ICU resources would be overwhelmed. Dynamic physical distancing could maintain health-system capacity and also allow periodic psychological and economic respite for populations.", "qid": 9, "docid": "lb2tuol2", "rank": 38, "score": 6.790799140930176}, {"content": "Title: Long time frames to detect the impact of changing COVID-19 control measures Content: Background: Many countries have implemented population-wide interventions such as physical distancing measures, in efforts to control COVID-19. The extent and success of such measures has varied. Many jurisdictions with declines in reported COVID-19 cases are moving to relax measures, while others are continuing to intensify efforts to reduce transmission. Aim: We aim to determine the time frame between a change in COVID-19 measures at the population level and the observable impact of such a change on cases. Methods: We examine how long it takes for there to be a substantial difference between the cases that occur following a change in control measures and those that would have occurred at baseline. We then examine how long it takes to detect a difference, given delays and noise in reported cases. We use changes in population-level (e.g., distancing) control measures informed by data and estimates from British Columbia, Canada. Results: We find that the time frames are long: it takes three weeks or more before we might expect a substantial difference in cases given a change in population-level COVID-19 control, and it takes slightly longer to detect the impacts of the change. The time frames are shorter (11-15 days) for dramatic changes in control, and they are impacted by noise and delays in the testing and reporting process, with delays reaching up to 25-40 days. Conclusion: The time until a change in broad control measures has an observed impact is longer than is typically understood, and is longer than the mean incubation period (time between exposure than onset) and the often used 14 day time period. Policy makers and public health planners should consider this when assessing the impact of policy change, and efforts should be made to develop rapid, consistent real-time COVID-19 surveillance.", "qid": 9, "docid": "ti92jbpz", "rank": 39, "score": 6.759300231933594}, {"content": "Title: Effects of memory on the shapes of simple outbreak trees Content: Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens\u2019 transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak\u2019s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.", "qid": 9, "docid": "mcdfcc8v", "rank": 40, "score": 6.734000205993652}, {"content": "Title: Can India stay immune enough to combat COVID\u201019 pandemic? An economic query Content: The COVID\u201019 pandemic has affected different sectors of the economy in an unprecedented way, and this article is an attempt to analyze the economic effect of the outbreak in India. However, before we assess the economic cost associated with the pandemic, we economists fully consider the outbreak as a human tragedy. There has not been any econometric technique that can account the countless human sufferings that the crisis has brought. Through this article, we address several important research questions and demonstrate India's strength to stay immune to combat COVID\u201019 pandemic. The research questions are as follows. First, what will be the effect of COVID\u201019 on the Indian economy and how does it affect the different sectors of the economy? Second, how does the pandemic affect the bilateral trade relation between India and China? Third, we question the role of the public health system in dealing with the outbreak of the virus in India. This article also presents the growth projection of the Indian economy by different economic agents. We finally conclude the article by mentioning a few policy recommendations for the Indian economy.", "qid": 9, "docid": "gw6zi5qn", "rank": 41, "score": 6.73390007019043}, {"content": "Title: Resilience in the time of pandemic: The experience of community pharmacists in Ontario during COVID-19 Content: BACKGROUND: As a result of the COVID-19 pandemic, there has been a significant disruption of the practice of pharmacy. Importantly, in many parts of the world, this disruption occurred literally overnight, requiring pharmacists to demonstrate significant adaptability and resiliency in order to manage continuing and in some cases expanding needs of patients. OBJECTIVES: The objective of this research was to characterize how community pharmacy in Ontario (Canada) responded to the COVID-19 pandemic of winter/spring 2020, in particula in understanding what factors may influence or predict resiliency of individual practitioners and their workplaces. METHODS: One-on-one interviews mediated through technology (Microsoft Teams) were used, following a semi-structured interview protocol. Verbatim transcripts were produced and analyzed by two independent researchers, using an inductive coding process to identify and characterize themes. RESULTS: A total of 21 pharmacists participated in this study. Six themes were identified: a) use of and comfort with technology; b) early adoption of corporate and professional guidance; c) workplaces that emphasized task-focus rather than multi-tasking were more resilient; d) scheduling methods and practices in the workplace are important for personal resilience; e) dedicated specialty staff allowed pharmacists to focus on their work; and f) provision of personal protective equipment was essential. CONCLUSIONS: Traditionally, resilience in professional practice has been characterized as a personal, not a workplace, issue. This study suggests that personal resiliency for pharmacists requires substantial workplace support; further work in this area is required to better understand how pharmacists adapt to complex and difficult situations such as pandemics.", "qid": 9, "docid": "3a1vmckt", "rank": 42, "score": 6.731200218200684}, {"content": "Title: Resilience in the time of pandemic: The experience of community pharmacists during COVID-19 Content: BACKGROUND: As a result of the COVID-19 pandemic, there has been a significant disruption of the practice of pharmacy. Importantly, in many parts of the world, this disruption occurred literally overnight, requiring pharmacists to demonstrate significant adaptability and resiliency in order to manage continuing and in some cases expanding needs of patients. OBJECTIVES: The objective of this research was to characterize how community pharmacy in Ontario (Canada) responded to the COVID-19 pandemic of winter/spring 2020, in particular in understanding what factors may influence or predict resiliency of individual practitioners and their workplaces. METHODS: One-on-one interviews mediated through technology (Microsoft Teams) were used, following a semi-structured interview protocol. Verbatim transcripts were produced and analyzed by two independent researchers, using an inductive coding process to identify and characterize themes. RESULTS: A total of 21 pharmacists participated in this study. Six themes were identified: a) use of and comfort with technology; b) early adoption of corporate and professional guidance; c) workplaces that emphasized task-focus rather than multi-tasking were more resilient; d) scheduling methods and practices in the workplace are important for personal resilience; e) dedicated specialty staff allowed pharmacists to focus on their work; and f) provision of personal protective equipment was essential. CONCLUSIONS: Traditionally, resilience in professional practice has been characterized as a personal, not a workplace, issue. This study suggests that personal resiliency for pharmacists requires substantial workplace support; further work in this area is required to better understand how pharmacists adapt to complex and difficult situations such as pandemics.", "qid": 9, "docid": "l970p9sd", "rank": 43, "score": 6.731199264526367}, {"content": "Title: Precautions and Procedures for Coronary and Structural Cardiac Interventions during the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology Content: Abstract The globe is currently in the midst of a COVID-19 pandemic resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology - Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the Cardiac Catheterization Laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients/staff and maintaining the overall healthcare resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. While some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.", "qid": 9, "docid": "hn1z0817", "rank": 44, "score": 6.691299915313721}, {"content": "Title: Precautions and Procedures for Coronary and Structural Cardiac Interventions During the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology Content: The globe is currently in the midst of a COVID-19 pandemic, resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology- Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the cardiac catheterization laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients and staff and maintaining the overall health care resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. Although some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.", "qid": 9, "docid": "v31uzr68", "rank": 45, "score": 6.691298961639404}, {"content": "Title: Canadian banks\u2019 responses to COVID-19: a strategic positioning analysis Content: The Canadian banking system is among the best in the world. Amid the COVID-19 pandemic, the world is challenged and banks are expected to rescue society. Businesses are revising, repurposing, and reinventing their products and services to address people\u2019s needs. In this context, this article seeks to understand how Canada\u2019s banks are supporting their clients and communities, during the current health crisis. Content analysis was conducted to analyse Canada\u2019s ten largest banks\u2019 supporting actions towards the pandemic, leading to 125 documents and 19 different actions consulted. Based on the data, a combination of hierarchical clustering and multidimensional scaling was conducted. Following a CSR approach, three clusters of banks are identified: sweeping actions, cautious actions, and wait & see, highlighting that while most banks are doing little to help their stakeholders, three of them have a proactive and strong commitment to their clients and communities in these times of need.", "qid": 9, "docid": "r0ach2jn", "rank": 46, "score": 6.678999900817871}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 9, "docid": "kgifmjvb", "rank": 47, "score": 6.666999816894531}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country\u2019s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world\u2019s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada\u2019s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 9, "docid": "wmfcey6f", "rank": 48, "score": 6.666998863220215}, {"content": "Title: COVID-19 and careers: On the futility of generational explanations Content: It is common to broadly group people of different ages into \"generations\" and to speak of distinctions between such groups in terms of \"generational differences.\" The problem with this practice, is that there exists no credible scientific evidence that (a) generations exist, (b) that people can be reliably classified into generational groups, and (c) that there are demonstrable differences between such groups. We have already noted an emerging generationalized rhetoric that has characterized how people of different ages have been affected by and reacted to the COVID-19 pandemic. These narratives have been especially present in discussions of how work and careers will be affected by this crisis. In this essay, we outline problems with applying the concept of generations, especially for researchers seeking explanations for how COVID-19 will affect careers and career development. We urge researchers to eschew the notion of generations and generational differences and consider alternative lifespan development theoretical frameworks that better capture age-graded processes.", "qid": 9, "docid": "6xsisjlf", "rank": 49, "score": 6.6539998054504395}, {"content": "Title: COVID-19 and careers: On the futility of generational explanations Content: Abstract It is common to broadly group people of different ages into \u201cgenerations\u201d and to speak of distinctions between such groups in terms of \u201cgenerational differences.\u201d The problem with this practice, is that there exists no credible scientific evidence that (a) generations exist, (b) that people can be reliably classified into generational groups, and (c) that there are demonstrable differences between such groups. We have already noted an emerging generationalized rhetoric that has characterized how people of different ages have been affected by and reacted to the COVID-19 pandemic. These narratives have been especially present in discussions of how work and careers will be affected by this crisis. In this essay, we outline problems with applying the concept of generations, especially for researchers seeking explanations for how COVID-19 will affect careers and career development. We urge researchers to eschew the notion of generations and generational differences and consider alternative lifespan development theoretical frameworks that better capture age-graded processes.", "qid": 9, "docid": "qorwfuqk", "rank": 50, "score": 6.653998851776123}, {"content": "Title: COVID\u201019 and Indigenous Peoples: An imperative for action Content: Every person on Earth has been affected in some way by the coronavirus disease (COVID-19) pandemic. However, there is a marked inequity in the impact and threat of the disease for the 370 million Indigenous Peoples worldwide. While honouring diversity in peoples and cultures, this editorial (written by a collaborative of Indigenous nurses from Australia, Aotearoa (New Zealand), Canada, the United States of America and Central America), explores contemporary issues raised for Indigenous communities by this latest public health emergency. Please note, while we may describe a situation about a specific Indigenous group, readers can be assured that the issues we raise are endemic across colonised Indigenous communities globally.", "qid": 9, "docid": "hqv9wi5u", "rank": 51, "score": 6.626399993896484}, {"content": "Title: Fear, affective semiosis, and management of the pandemic crisis: Covid-19 as semiotic vaccine? Content: The COVID-19 pandemic represents an extraordinary challenge to clinicians, health care institutions and policymakers. The paper outlines a psychoanalytically grounded semiotic-cultural psychological interpretation of such a scenario. First, we underline how the actual emotional reaction (mainly of fear) of our society is a marker of how the mind functions in conditions of affective activation related to heightened uncertainty: it produces global, homogenizing and generalizing embodied interpretations of reality, at the cost of more fine-grained and differentiated analytical thought. Such a process, called affective semiosis, represents an adaptive response to the emergency in the short-term. Second, we argue that this adaptive value provided by affective semiosis will be reduced when we have to deal with the process of managing the transition to the post-crisis and the governance of the medium and long-term impact of the crisis. Third, we suggest that, in order to manage the pandemic crisis on a longer temporal frame, affective semiosis has to be integrated with less generalized and more domain-specific ways of interpreting reality. To this end, semiotic capital (i.e., culturally-mediated symbolic resources) should be promoted in order to enable people to interiorize the supra-individual and collective dimension of life. Accordingly, COVID-19 is proposed as a semiotic vaccine, a disruption in our everyday life routines which has the potential of opening the way to a semiotic re-appropriation of the collective dimensions of our experience.", "qid": 9, "docid": "paqah5h6", "rank": 52, "score": 6.605800151824951}, {"content": "Title: Talk COVID to Me: Language Rights and Canadian Government Responses to the Pandemic Content: Since the COVID-19 outbreak, a gradual loosening of linguistic obligations in public institutions and governments has been observed in various jurisdictions in Canada. This article argues that in addition to legal requirements to provide minority language services, it is not justifiable for governments to suspend or curtail such services in an emergency situation, for reasons pertaining to public safety and public health. After performing a survey and analysis of government actions against their constitutional, legislative, and policy language obligations to highlight best practices and deficiencies, we discuss the policy implications of these actions. In conclusion, the article considers how governments could better uphold their language obligations in times of emergency.", "qid": 9, "docid": "cq6f8v94", "rank": 53, "score": 6.601500034332275}, {"content": "Title: Analysis of Outbreak and Global Impacts of the COVID-19 Content: Corona viruses are a large family of viruses that are not only restricted to causing illness in humans but also affect animals such as camels, cattle, cats, and bats, thus affecting a large group of living species The outbreak of Corona virus in late December 2019 (also known as COVID-19) raised major concerns when the outbreak started getting tremendous While the first case was discovered in Wuhan, China, it did not take long for the disease to travel across the globe and infect every continent (except Antarctica), killing thousands of people Since it has become a global concern, different countries have been working toward the treatment and generation of vaccine, leading to different speculations While some argue that the vaccine may only be a few weeks away, others believe that it may take some time to create the vaccine Given the increasing number of deaths, the COVID-19 has caused havoc worldwide and is a matter of serious concern Thus, there is a need to study how the disease has been propagating across continents by numbers as well as by regions This study incorporates a detailed description of how the COVID-19 outbreak started in China and managed to spread across the globe rapidly We take into account the COVID-19 outbreak cases (confirmed, recovered, death) in order to make some observations regarding the pandemic Given the detailed description of the outbreak, this study would be beneficial to certain industries that may be affected by the outbreak in order to take timely precautionary measures in the future Further, the study lists some industries that have witnessed the impact of the COVID-19 outbreak on a global scale", "qid": 9, "docid": "x51o4gyn", "rank": 54, "score": 6.577099800109863}, {"content": "Title: The Coronavirus 2019 pandemic in Canada: the impact of public health interventions on the course of the outbreak in Alberta and other provinces Content: Background: The SARS-CoV-2 disease 2019 (COVID-19) pandemic has spread across the world with varying impact on health systems and outcomes. We assessed how the type and timing of public- health interventions impacted the course of the outbreak in Alberta and other Canadian provinces. Methods: We used publicly-available data to summarize rates of laboratory data and mortality in relation to measures implemented to contain the outbreak and testing strategy. We estimated the transmission potential of SARS-CoV-2 before the state of emergency declaration for each province (R0) and at the study end date (Rt). Results: The first cases were confirmed in Ontario (January 25) and British Columbia (January 28). All provinces implemented the same health-policy measures between March 12 and March 30. Alberta had a higher percentage of the population tested (3.8%) and a lower mortality rate (3/100,000) than Ontario (2.6%; 11/100,000) or Quebec (3.1%; 31/100,000). British Columbia tested fewer people (1.7%) and had similar mortality as Alberta. Data on provincial testing strategies were insufficient to inform further analyses. Mortality rates increased with increasing rates of lab- confirmed cases in Ontario and Quebec, but not in Alberta. R0 was similar across all provinces, but varied widely from 2.6 (95% confidence intervals 1.9-3.4) to 6.4 (4.3-8.5), depending on the assumed time interval between onset of symptoms in a primary and a secondary case (serial interval). The outbreak is currently under control in Alberta, British Columbia and Nova Scotia (Rt <1). Interpretation: COVID-19-related health outcomes varied by province despite rapid implementation of similar health-policy interventions across Canada. Insufficient information about provincial testing strategies and a lack of primary data on serial interval are major limitations of existing data on the Canadian COVID-19 outbreak.", "qid": 9, "docid": "v346cpkl", "rank": 55, "score": 6.557000160217285}, {"content": "Title: Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment Content: The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue \u201cstay-at-home\u201d orders to contain the virus\u2019s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory\u2019s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.", "qid": 9, "docid": "gjdza9bh", "rank": 56, "score": 6.545400142669678}, {"content": "Title: Caring for Frail Older Adults During COVID-19: Integrating Public Health Ethics into Clinical Practice Content: During the coronavirus disease 2019 (COVID-19) pandemic, principles from both clinical and public health ethics cue clinicians and healthcare administrators to plan alternatives for frail older adults who prefer to avoid critical care, and for when critical care is not available due to crisis triaging. This article will explore the COVID-19 Ethical Decision Making Framework, published in British Columbia (BC), Canada, to familiarize clinicians and policy makers with how ethical principles can guide systems change, in the service of frail older adults. In BC, the healthcare system has launched resources to support clinicians in proactive advance care planning discussions, and is providing enhanced supportive and palliative care options to residents of long-term care facilities. If the pandemic truly overwhelms the healthcare system, frailty, but not age alone, provides a fair and evidence-based means of triaging patients for critical care and could be included into ventilator allocation frameworks.", "qid": 9, "docid": "y8zosieg", "rank": 57, "score": 6.545399188995361}, {"content": "Title: Caring for Frail Older Adults During COVID\u201019: integrating public health ethics into clinical practice Content: During the COVID\u201019 pandemic, principles from both clinical and public health ethics cue clinicians and health care administrators to plan alternatives for frail older adults who prefer to avoid critical care, and for when critical care is not available due to crisis triaging. This paper will explore the COVID\u201019 Ethical Decision Making Framework, published in British Columbia, Canada, to familiarize clinicians and policy makers with how ethical principles can guide systems change, in the service of frail older adults. In British Columbia, the health care system has launched resources to support clinicians in proactive advance care planning discussions, and is providing enhanced supportive and palliative care options to residents of long term care facilities. If the pandemic truly overwhelms the healthcare system, frailty, but not age alone, provides a fair and evidence\u2010based means of triaging patients for critical care and could be included into ventilator allocation frameworks. This article is protected by copyright. All rights reserved.", "qid": 9, "docid": "yj2wrr9t", "rank": 58, "score": 6.545398235321045}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60-95%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood.", "qid": 9, "docid": "hsr2ue28", "rank": 59, "score": 6.533299922943115}, {"content": "Title: Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazi Content: The current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.", "qid": 9, "docid": "zhcamsqa", "rank": 60, "score": 6.50029993057251}, {"content": "Title: The impact of COVID\u201019 on food retail and food service in Canada: Preliminary assessment Content: COVID\u201019 has imposed a series of unique challenges on the food retail and food service sectors in Canada. Almost overnight, the roughly 30% of the food dollar that Canadians have been spending on food away from home has shifted to retail.", "qid": 9, "docid": "lz0chxab", "rank": 61, "score": 6.48330020904541}, {"content": "Title: The COVID\u201019 Pandemic: Anticipating its Effects on Canada's Agricultural Trade Content: With the deep recession now forecast for the world economy, trade can be expected to fall even more steeply. Agricultural trade will be less significantly affected, being insulated by its relatively low income elasticities of demand. However, a drop in the range of 12 to 20 percent in real trade value should be expected. Canada can be expected to share in this, but, within agricultural exports, cereals will be least affected. This minimal expected impact to cereals stems from the risk of wheat export bans by Russia and Kazakhstan, due to the resulting increase in wheat prices. Livestock, pulses, and horticulture can be expected to face a larger decline in trade prospects and revenues. An equally large threat to falling incomes in our trade partners is their policy responses, particularly the potential increase in import restrictions. These may take the form of more costly inspections, tightened SPS and food safety regulations, and protectionist measures from competing domestic producers. This article is protected by copyright. All rights reserved", "qid": 9, "docid": "p7ig5rw2", "rank": 62, "score": 6.466300010681152}, {"content": "Title: The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda Content: Abstract International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform \u201cessential\u201d tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "qid": 9, "docid": "lc4q55ei", "rank": 63, "score": 6.464200019836426}, {"content": "Title: The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda Content: International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform \"essential\" tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "qid": 9, "docid": "yvnjspsc", "rank": 64, "score": 6.464199066162109}, {"content": "Title: Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement Content: The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L\u2019Association canadienne de g\u00e9rontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "qid": 9, "docid": "4kojv5pv", "rank": 65, "score": 6.426400184631348}, {"content": "Title: Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement Content: The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L'Association canadienne de g\u00e9rontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "qid": 9, "docid": "fbq90100", "rank": 66, "score": 6.426399230957031}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60\u201395%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-020-00367-6) contains supplementary material, which is available to authorized users.", "qid": 9, "docid": "3p9yc6ti", "rank": 67, "score": 6.424699783325195}, {"content": "Title: Syndromic Surveillance for COVID-19 in Canada Content: Background: Syndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. Methods: Data sources consisted of two distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. Results: We found that 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month over March-April 2020. Across the three surveys, SARS-CoV-2-testing was reported in 2-9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Metis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. Interpretation: The low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of current SARS-CoV-2 testing rates.", "qid": 9, "docid": "cxoom0tu", "rank": 68, "score": 6.42080020904541}, {"content": "Title: Post-Covid-19 Education and Education Technology \u2018Solutionism\u2019: a Seller\u2019s Market Content: The Covid-19 pandemic and the social distancing that followed have affected all walks of society, also education. In order to keep education running, educational institutions have had to quickly adapt to the situation. This has resulted in an unprecedented push to online learning. Many, including commercial digital learning platform providers, have rushed to provide their support and \u2018solutions\u2019, sometimes for free. The Covid-19 pandemic has therefore also created a sellers\u2019 market in ed-tech. This paper employs a critical lens to reflect on the possible problems arising from hasty adoption of commercial digital learning solutions whose design might not always be driven by best pedagogical practices but their business model that leverages user data for profit-making. Moreover, already before Covid-19, there has been increasing critique of how ed-tech is redefining and reducing concepts of teaching and learning. The paper also challenges the narrative that claims, \u2018education is broken, and it should and can be fixed with technology\u2019. Such technologization, often seen as neutral, is closely related to educationalization, i.e. imposing growing societal problems for education to resolve. Therefore, this is a critical moment to reflect how the current choices educational institutions are making might affect with Covid-19 education and online learning: Will they reinforce capitalist instrumental view of education or promote holistic human growth? This paper urges educational leaders to think carefully about the decisions they are currently making and if they indeed pave the way to a desirable future of education.", "qid": 9, "docid": "ybpy2t64", "rank": 69, "score": 6.377600193023682}, {"content": "Title: Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada Content: We explored the impact of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada using a previously described age- and health-status stratified transmission model. The model was fit to confirmed cases occupying intensive care unit (ICU) beds and mortality among hospitalized COVID-19 cases for the time period 19 March to 26 April 2020. We projected that mortality would have been 4.6-fold what was observed had physical distancing measures not been implemented in the province. Relaxation of physical distancing measures without compensatory increases in case detection, isolation, and/or contact tracing was projected to result in resurgence of disease activity. Return to normal or near-normal levels of contact would rapidly result in cases exceeding ICU capacity. Maintaining physical distancing for a longer period of time, allowing for the initial wave of infections to subside, delayed this resurgence, but the level of contacts post-restrictive distancing was the major factor determining how quickly ICU capacity was expected to be overwhelmed. Using a model, we demonstrate the marked impact strong public health measures had in reducing ICU admissions and mortality in Ontario. We also show that this hard-earned success is tenuous: relaxation of physical distancing measures in the near-term is projected to result in a rapid resurgence of disease activity.", "qid": 9, "docid": "bp2ilntr", "rank": 70, "score": 6.373199939727783}, {"content": "Title: How long will social distancing take to work? Experts weigh in on Canada's COVID-19 response Content:", "qid": 9, "docid": "ag6gwy74", "rank": 71, "score": 6.372799873352051}, {"content": "Title: How long will social distancing take to work? Experts weigh in on Canada's COVID-19 response. Content:", "qid": 9, "docid": "wb32j7s0", "rank": 72, "score": 6.372798919677734}, {"content": "Title: Proceedings of the OMS COVID-19 Response Conference Content: The coronavirus disease 2019 (COVID-19) pandemic has affected the world in unprecedented ways. It is clear that this pandemic, unlike any public health challenge in recent memory, has the potential to fundamentally alter the delivery of many healthcare services, including the practice of oral and maxillofacial surgery. In response to this global health crisis, the Oral and Maxillofacial Surgery (OMS) COVID-19 Response Conference was held virtually on April 9, 2020, organized by oral and maxillofacial surgeons (OMSs) and administrators from multiple institutions to provide a forum for OMSs to discuss how COVID-19 has affected the specialty. As evidence-based information on COVID-19 continues to emerge, the present report serves as a method to disseminate the current opinions and management strategies from a variety of experts in OMS.", "qid": 9, "docid": "h8txyoj3", "rank": 73, "score": 6.370999813079834}, {"content": "Title: Letter to the editor in response to: COVID-19 pandemic and challenges for socio-economic issues, healthcare and national programs in India (Gopalan and Misra) Content: Article by Gopalan and Misra is very informative and covers the current challenges arising due to COVID-19. Further, authors has attempted to explore the various socioeconomic and medical aspects affected during this COVID-19 pandemic. It starts with the economic issues, social impacts, cultural influences, and the health related national programs which are regularly getting impacted owing to the ongoing epidemic. The paper throws light on how the pandemic has strongly affected the jobs, businesses transportation, travel, and other sectors which ultimately influence the social-economic balance of the society. This has further led to the decrease in the GDP of the country. The daily wagers and the local business personnel are the most affected ones during this period.", "qid": 9, "docid": "380sajt9", "rank": 74, "score": 6.364099979400635}, {"content": "Title: The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study Content: BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people\u2019s mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.", "qid": 9, "docid": "8r0orhkm", "rank": 75, "score": 6.360599994659424}, {"content": "Title: The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study Content: BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people's mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.", "qid": 9, "docid": "fjss4e92", "rank": 76, "score": 6.360599040985107}, {"content": "Title: Evidence\u2010Loving Rockstar Chief Medical Officers: Female Leadership Amidst COVID\u201019 in Canada Content: This paper presents a feminist poststructuralist inquiry perspective on how news and social media discourse around the COVID\u201019 pandemic is presenting a potential shift in hegemonic representations of masculine leadership. I am informed by organizational rules and sensemaking theories, and consider how Canadian and international female leaders are showing resilience, emotion, and vulnerability as they help lead their countries through these uncertain times. I reflexively ground my observations in my own sensemaking and personal experiences. Despite reservations, I am hopeful. There are indications that the \u201crules of the game\u201d are starting to be challenged, and feminine frameworks that question traditional gender roles are disrupting conceptions around \u201cbusiness as usual.\u201d", "qid": 9, "docid": "uoxn740r", "rank": 77, "score": 6.360099792480469}, {"content": "Title: Psychiatric Training During a Global Pandemic: How COVID-19 Has Affected Clinical Care, Teaching, and Trainee Well-Being. Content: The COVID-19 pandemic has altered many aspects of personal and professional life, including how psychiatry is practiced and how trainees are taught. This Open Forum outlines the challenges faced by psychiatric training directors in adult as well as child and adolescent psychiatry in meeting the educational needs of trainees amid this international crisis. Prioritizing trainee protection and education as well as high-quality treatment for patients, the authors discuss effective communication strategies, rapid telepsychiatry expansion into clinical practice, curricular adjustments, and the importance of well-being. This Open Forum concludes with reflections and considerations for training directors as they prepare for subsequent stages of the COVID-19 pandemic.", "qid": 9, "docid": "4jgjw56d", "rank": 78, "score": 6.351399898529053}, {"content": "Title: Psychiatric Training During a Global Pandemic: How COVID-19 Has Affected Clinical Care, Teaching, and Trainee Well-Being Content: The COVID-19 pandemic has altered many aspects of personal and professional life, including how psychiatry is practiced and how trainees are taught. This Open Forum outlines the challenges faced by psychiatric training directors in adult as well as child and adolescent psychiatry in meeting the educational needs of trainees amid this international crisis. Prioritizing trainee protection and education as well as high-quality treatment for patients, the authors discuss effective communication strategies, rapid telepsychiatry expansion into clinical practice, curricular adjustments, and the importance of well-being. This Open Forum concludes with reflections and considerations for training directors as they prepare for subsequent stages of the COVID-19 pandemic.", "qid": 9, "docid": "a3z050go", "rank": 79, "score": 6.351398944854736}, {"content": "Title: COVID-19's Impact on Italian Urology. Content: The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.", "qid": 9, "docid": "2tqxj0ua", "rank": 80, "score": 6.342299938201904}, {"content": "Title: COVID-19's Impact on Italian Urology Content: The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.", "qid": 9, "docid": "j5sb8cvl", "rank": 81, "score": 6.342298984527588}, {"content": "Title: Public health in Canada: Evolution, meaning and a new paradigm for respiratory therapy Content: Chronic disease burden in Canada poses an imminent public health threat. The impact of respiratory disease in Canada alone is significant, affecting one in five and leading any other cause of repeat hospitalization in all age groups. Public health action is considered to be an important means of addressing these issues. Historical understanding of health has evolved to support the adoption of paradigms by professions that recognize the limitations of medical intervention in addressing the fundamental basis of disease when compared with the broader public health perspective. Several key historical events have shaped this understanding in the Canadian context including the Lalonde and Epp reports, and public health emergencies such as the severe acute respiratory syndrome outbreak in 2003. The profession of respiratory therapy has historically existed within a medicalized paradigm of practice; however, forces both internal and external to the profession are pressuring it to consider adopting broader social-and population-based approaches. As a rapidly evolving profession, there is a need to explore emerging areas of practice opportunities in the discipline. Investigating alternative knowledge and ideology can ensure that effective strategies for addressing the contemporary respiratory heath needs of Canadians are undertaken. The present article explores the rationale for a public health- and population-based approach to health in general, and its applicability to the respiratory therapist\u2019s role in addressing respiratory health-related issues in Canada.", "qid": 9, "docid": "7n8rrvrs", "rank": 82, "score": 6.340700149536133}, {"content": "Title: Coronavirus: Where Has All the Health Economics Gone? Content: As the coronavirus disease 2019 (COVID-19) pandemic continues to unfold there is an untold number of trade-offs being made in every country around the globe. The experience in the United Kingdom and Canada to date has not seen much uptake of health economics methods. We provide some thoughts on how this could take place, specifically in three areas. Firstly, this can involve understanding the impact of lockdown policies on national productivity. Secondly, there is great importance in studying trade-offs with respect to enhancing health system capacity and the impact of the mix of private-public financing. Finally, there are key trade-offs that will continue to be made both in terms of access to testing and ventilators which would benefit greatly from economic appraisal. In short, health economics could - and we would argue most certainly should - play a much more prominent role in policy-making as it relates to the current as well as future pandemics.", "qid": 9, "docid": "llpb13t6", "rank": 83, "score": 6.330399990081787}, {"content": "Title: Mathematical modeling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada Content: Background: We evaluated how non-pharmaceutical interventions could be used to control the COVID-19 pandemic and reduce the burden on the healthcare system Methods: Using an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada, we compared a base case with limited testing, isolation, and quarantine to scenarios with: enhanced case finding;restrictive social distancing measures;or a combination of enhanced case finding and less restrictive social distancing Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected ICU bed occupancy We present median and credible intervals (CrI) from 100 replicates per scenario using a two-year time horizon Results: We estimated that 56% (95% CrI: 42-63%) of the Ontario population would be infected over the course of the epidemic in the base case At the epidemic peak, we projected 107,000 (95% CrI: 60,760-149,000) cases in hospital and 55,500 (95% CrI: 32,700-75,200) cases in ICU For fixed duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive social distancing estimated to have the greatest effect Longer duration interventions were more effective Dynamic interventions were projected to reduce the proportion of the population infected at the end of the two-year period Dynamic social distancing interventions could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity Interpretation: Without significant social distancing or a combination of moderate social distancing with enhanced case finding, we project that ICU resources would be overwhelmed Dynamic social distancing could maintain health system capacity and also allow periodic psychological and economic respite for populations ### Competing Interest Statement The authors have declared no competing interest ### Funding Statement The research was supported by a grant to DNF from the Canadians Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360) ### Author Declarations All relevant ethical guidelines have been followed;any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials gov I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance) Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable Yes Data are available from the corresponding author on request", "qid": 9, "docid": "e4pr78n0", "rank": 84, "score": 6.276400089263916}, {"content": "Title: The legal extension of the role of pharmacists in light of the COVID-19 global pandemic Content: BACKGROUND: The COVID-19 epidemic has affected every area of life. The greatest challenge has been to adapt the functioning of the health service to prevent the spread of the epidemic and to help infected patients. This has required the involvement of not only doctors and nurses, but also pharmacists. In the face of this pandemic, governments in many countries have granted pharmacists greater authority. OBJECTIVES: The purpose of this paper is to review the legal extension of the role of pharmacists in light of the COVID-19 pandemic. The review considers recent changes in European countries, Canada, and the United States. METHODS: A literature review was performed to summarise knowledge about the extension of the role of pharmacists during the pandemic period. Key articles were retrieved mainly from PubMed and Google Scholar, using the terms \"COVID-19\", \"2019-nCoV\", \"coronavirus\", and \"pandemic\" in combination with \"pharmacist\" as keywords for our search. We included scientific publications from February 1, 2019 to May 15, 2020. RESULTS: Pharmacists have been given numerous opportunities so that they can actively join in the fight against the virus. Some of the novel legal extensions aimed at aiding overloaded healthcare systems are as follows: authorisation to prepare hand and surface disinfectants, eligibility to renew chronic treatment prescriptions, as well as filling pro auctore and pro familia prescriptions by pharmacists, performing COVID-19, influenza, and Group A Streptococcus screening tests, and vaccine administration. Moreover, many countries have facilitated Internet services, such as virtual medical consultations, e-prescriptions, and home drug delivery - to promote social distancing among patients. To mitigate drug shortages, the following strategies have been implemented: alternative sourcing, strength, generic, or therapeutic substitution, and preparing compounded formulations at the pharmacy. CONCLUSIONS: Novel legal extensions have allowed exploitation of the full potential ofpharmacists worldwide, aiding the limited resources of overloaded healthcare systems.", "qid": 9, "docid": "bec2onjt", "rank": 85, "score": 6.266600131988525}, {"content": "Title: The legal extension of the role of pharmacists in light of the COVID-19 global pandemic Content: BACKGROUND: The COVID-19 epidemic has affected every area of life. The greatest challenge has been to adapt the functioning of the health service to prevent the spread of the epidemic and to help infected patients. This has required the involvement of not only doctors and nurses, but also pharmacists. In the face of this pandemic, governments in many countries have granted pharmacists greater authority. OBJECTIVES: The purpose of this paper is to review the legal extension of the role of pharmacists in light of the COVID-19 pandemic. The review considers recent changes in European countries, Canada, and the United States. METHODS: A literature review was performed to summarise knowledge about the extension of the role of pharmacists during the pandemic period. Key articles were retrieved mainly from PubMed and Google Scholar, using the terms \u201cCOVID\u201019\u201d, \u201c2019\u2010nCoV\u201d, \u201ccoronavirus\u201d, and \u201cpandemic\u201d in combination with \u201cpharmacist\u201d as keywords for our search. We included scientific publications from February 1, 2019 to May 15, 2020. RESULTS: Pharmacists have been given numerous opportunities so that they can actively join in the fight against the virus. Some of the novel legal extensions aimed at aiding overloaded healthcare systems are as follows: authorisation to prepare hand and surface disinfectants, eligibility to renew chronic treatment prescriptions, as well as filling pro auctore and pro familia prescriptions by pharmacists, performing COVID-19, influenza, and Group A Streptococcus screening tests, and vaccine administration. Moreover, many countries have facilitated Internet services, such as virtual medical consultations, e-prescriptions, and home drug delivery \u2013 to promote social distancing among patients. To mitigate drug shortages, the following strategies have been implemented: alternative sourcing, strength, generic, or therapeutic substitution, and preparing compounded formulations at the pharmacy. CONCLUSIONS: Novel legal extensions have allowed exploitation of the full potential ofpharmacists worldwide, aiding the limited resources of overloaded healthcare systems.", "qid": 9, "docid": "qheq9lc8", "rank": 86, "score": 6.266599178314209}, {"content": "Title: Do Quarantine Experiences and Attitudes Towards COVID-19 Affect the Distribution of Mental Health in China? A Quantile Regression Analysis Content: While quarantine has become a widely used control strategy during the outbreak of the 2019 novel coronavirus disease (COVID-19), empirical research on whether and to what extent quarantine and attitudes towards COVID-19 affect mental health is scant. Using a cross-sectional online survey, this paper is the first from the Chinese outbreak to investigate how quarantine experiences and attitudes towards COVID-19 are related to mental health, and how these relationships change across the distribution of mental health scores. Using quantile regression analysis, we found that home self-quarantine is associated with a decrease in depression and an increase in happiness, while community-level quarantine is associated with decreased happiness, especially for those in the lower happiness quantile. We also found that favorable attitudes towards COVID-19 regarding the credibility of real-time updates and confidence in the epidemic control are associated with lower levels of depression and higher levels of happiness. These effects are stronger in the upper quantile of depression and the median quantile of happiness.", "qid": 9, "docid": "2pcc8dmt", "rank": 87, "score": 6.250400066375732}, {"content": "Title: Research preparedness paves the way to respond to pandemic H1N1 2009 influenza virus. Content: The international community has been preparing for an influenza pandemic because of the threat posed by H5N1 avian influenza. Over the past several years, Canada has dedicated funding to boost capacity for research, and public health and health care system readiness and response in the event of a pandemic. The current H1N1/09 influenza pandemic is now testing our readiness. From a research perspective, the present commentary discusses how have we prepared, along with the research gaps. We conclude that: sources of pandemics are not always predictable; investment in the past few years has paid off in a rapid response to pandemic H1N1/09 virus in Canada; and research to meet the challenges of infectious diseases has to be done on an ongoing long-term basis, and its funding has to be flexible, available and predictable to maintain capacity and expertise. In addition, new vaccine technologies are needed to develop and produce vaccines for public health emergencies in a timely fashion.", "qid": 9, "docid": "nwwkw2iq", "rank": 88, "score": 6.2357001304626465}, {"content": "Title: Uptrend in distress and psychiatric symptomatology in pregnant women during the COVID-19 pandemic. Content: INTRODUCTION Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development and later psychopathologies. The study aimed to determine the extent to which the Coronavirus disease 2019 (COVID-19) pandemic may aggravate pregnant women prenatal distress and psychiatric symptomatology. MATERIAL AND METHODS Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n=496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n=1258) was recruited online during the pandemic from April 2 to April 13 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II) and Positive and Negative Affect Schedule (PANAS). RESULTS The 1754 pregnant women (Mage =29.27, SD=4.23) were between 4 and 41 gestational weeks (M=24.80, SD=9.42), were generally educated (91.3% had post-high school training) and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' \u03bb=0.68, F6,1400 =108.50, p < 0.001, partial \u03b72 = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES=0.57), dissociative symptoms (ES=0.22 and 0.25), symptoms of post-traumatic stress disorder (ES=0.19), negative affectivity (ES = 0.96) and less positive affectivity (ES=0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms [OR=1.94, \u03c72(1)=10.05, p=.002]. Multiple regression analyses indicated that COVID-19 pregnant women having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. CONCLUSIONS Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.", "qid": 9, "docid": "8wb6u7dc", "rank": 89, "score": 6.234000205993652}, {"content": "Title: Statistical and Network-Based Analysis of Italian COVID-19 Data: Communities Detection and Temporal Evolution Content: The coronavirus disease (COVID-19) outbreak started in Wuhan, China, and it has rapidly spread across the world. Italy is one of the European countries most affected by COVID-19, and it has registered high COVID-19 death rates and the death toll. In this article, we analyzed different Italian COVID-19 data at the regional level for the period 24 February to 29 March 2020. The analysis pipeline includes the following steps. After individuating groups of similar or dissimilar regions with respect to the ten types of available COVID-19 data using statistical test, we built several similarity matrices. Then, we mapped those similarity matrices into networks where nodes represent Italian regions and edges represent similarity relationships (edge length is inversely proportional to similarity). Then, network-based analysis was performed mainly discovering communities of regions that show similar behavior. In particular, network-based analysis was performed by running several community detection algorithms on those networks and by underlying communities of regions that show similar behavior. The network-based analysis of Italian COVID-19 data is able to elegantly show how regions form communities, i.e., how they join and leave them, along time and how community consistency changes along time and with respect to the different available data.", "qid": 9, "docid": "ncenvbbc", "rank": 90, "score": 6.228499889373779}, {"content": "Title: Personal Protective Equipment during the COVID-19 pandemic and operative time in cesarean section: retrospective cohort study. Content: INTRODUCTION The covid-19 pandemic has meant a change in working protocols, as well as in Personal Protective Equipment (PPE). Obstetricians have had to adapt quickly to these changes without knowing how they affected their clinical practice. The aim of the present study was to evaluate how COVID-19 pandemic and PPE can affect operative time, operating room time, transfer into the operating room to delivery time and skin incision to delivery time in cesarean section. METHODS This is a single-center retrospective cohort study. Women with confirmed or suspected SARS-CoV-2 infection having a cesarean section after March 7th, 2020 during the COVID-19 pandemic were included in the study. For each woman with confirmed or suspected SARS-CoV-2 infection, a woman who had a cesarean section for the same indication during the COVID-19 pandemic and with similar clinical history but not affected by SARS-CoV-2 was included. RESULTS 42 cesarean sections were studied. The operating room time was longer in the COVID-19 confirmed or suspected women: 90 (73.0 to 110.0) versus 61 (48.0 to 70.5) minutes; p < .001. The transfer into the operating room to delivery time was longer, but not statistically significant, in urgent cesarean sections in COVID-19 confirmed or suspected women: 25.5 (17.5 to 31.75) versus 18.0 (10.0 to 26.25) minutes; p = .113. CONCLUSIONS There were no significant differences in the operative time, transfer into the operating room to delivery time and skin incision to delivery time when wearing PPE in cesarean section. The COVID-19 pandemic and the use of PPE resulted in a significant increase in operating room time.", "qid": 9, "docid": "mtap0bkz", "rank": 91, "score": 6.221199989318848}, {"content": "Title: The impact of severe acute respiratory syndrome on the use of and requirements for filters in Canada. Content: This article begins with a brief look at the epidemiology of SARS in Canada and then discusses barrier use and potential containment strategies that could be applied to the respiratory equipment and supportive procedures that have been implicated in the spread of SARS or other respiratory infections. The article ends with a discussion of how practice and regulations have changed in Canada since SARS and some suggestions on how practice or regulations could further improve.", "qid": 9, "docid": "mh23h29f", "rank": 92, "score": 6.218299865722656}, {"content": "Title: Uptrend in distress and psychiatric symptomatology in pregnant women during the coronavirus disease 2019 pandemic Content: INTRODUCTION: Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development, and later psychopathologies. The study aimed to determine the extent to which the coronavirus disease 2019 (COVID-19) pandemic may aggravate the prenatal distress and psychiatric symptomatology of pregnant women. MATERIAL AND METHODS: Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n = 496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n = 1258) was recruited online during the pandemic from 2 April to 13 April 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II), and Positive and Negative Affect Schedule (PANAS). RESULTS: The 1754 pregnant women (Mage = 29.27, SD = 4.23) were between 4 and 41 gestational weeks (M = 24.80, SD = 9.42), were generally educated (91.3% had post-high-school training), and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education, and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' &#955; = 0.68, F6,1400 = 108.50, P < .001, partial \u00ce\u00b72 = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES = 0.57), dissociative symptoms (ES = 0.22 and ES = 0.25), symptoms of post-traumatic stress disorder (ES = 0.19), and negative affectivity (ES = 0.96), and less positive affectivity (ES = 0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms (OR = 1.94, &#967;2 [1] = 10.05, P = .002). Multiple regression analyses indicated that pregnant women in the COVID-19 cohort having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. CONCLUSIONS: Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.", "qid": 9, "docid": "9ub8fgvu", "rank": 93, "score": 6.202499866485596}, {"content": "Title: Increased risk of endemic mosquito-borne diseases in Canada due to climate change. Content: There are currently over 80 species of mosquito endemic in Canada-although only a few of these carry pathogens that can cause disease in humans. West Nile virus, Eastern equine encephalitis virus and the California serogroup viruses (including the Jamestown Canyon and snowshoe hare viruses) are mosquito-borne viruses that have been found to cause human infections in North America, including in Canada. Over the last 20 years, the incidence of most of these endemic mosquito-borne diseases (MBD) has increased approximately 10% in Canada, due in large part to climate change. It is anticipated that both the mosquito lifecycle and virus transmission patterns will be affected by climate change, resulting in an increase in both the range and local abundance of several important mosquito species. Laboratory studies and mathematical modelling suggest that increased ambient temperatures, changes in precipitation and extreme weather events associated with climate change will likely continue to drive mosquito vector and MBD range expansion, increasing the duration of transmission seasons and leading to MBD-related epidemics. Furthermore, Canada's endemic MBDs have complex transmission cycles, involving multiple reservoir hosts (birds and mammals), multiple pathogens and multiple mosquito species-all of which may be sensitive to climate and other environmental changes, and making forecasting of potential emerging trends difficult. These expected climate-induced changes in mosquitoes and MBDs underline the need for continued (and expanded) surveillance and research to ensure timely and accurate evaluation of the risks to the public health of Canadians.", "qid": 9, "docid": "vyfg6c9d", "rank": 94, "score": 6.198400020599365}, {"content": "Title: Controlling SARS: a review on China\u2019s response compared with other SARS\u2010affected countries Content: Objective To summarise the major control measures implemented by severe acute respiratory syndrome (SARS)\u2010affected countries and to compare distinctive features of the Chinese approach to other affected Asian countries and Canada. Method Literature review. Results The realisation in March 2003 that SARS was spreading led affected countries to introduce measures such as rapid dissemination of information, early case detection and isolation, tracing and quarantining of SARS contacts, traveller screening, raising public awareness of risk and institution of stricter infection control in health care settings. SARS became a notifiable disease in China in mid\u2010April 2003, after which introduction of efficient nationwide control measures led to containment within 2 months. Countries differed in the timeliness of implementing control measures, the mode and extent to which these were enforced and in the resources available to do so. Conclusion SARS challenged the political and public health systems of all affected countries. It demanded rapid and decisive action to be taken, yet the comparison shows how difficult this was for an unknown new disease. Guangdong reacted rapidly but this pace was not continued by China for some time, which facilitated national and international spread. Once the Chinese government changed its policy, it developed an impressive control strategy involving the public which culminated in containment. The significance of timely information was perhaps the main lesson which the SARS epidemic taught.", "qid": 9, "docid": "1ocg0gj3", "rank": 95, "score": 6.173600196838379}, {"content": "Title: How is the lockdown affecting vet students? Content: Like most other professions in the UK, the veterinary profession has been hit hard by Covid-19. But how has it impacted on students? Alexia Yiannouli investigates.", "qid": 9, "docid": "gxqofw8x", "rank": 96, "score": 6.1616997718811035}, {"content": "Title: In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa Content: While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response.", "qid": 9, "docid": "2kyeiima", "rank": 97, "score": 6.160900115966797}, {"content": "Title: In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa. Content: While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response.", "qid": 9, "docid": "dau5bs2x", "rank": 98, "score": 6.1608991622924805}, {"content": "Title: Statistical and network-based analysis of Italian COVID-19 data: communities detection and temporal evolution Content: Coronavirus disease (COVID-19) outbreak started at Wuhan, China, and it has rapidly spread across China and many other countries. Italy is one of the European countries most affected by the COVID-19 disease, and it has registered high COVID-19 death rates and the death toll. In this article, we analyzed different Italian COVID-19 data at the regional level for the period February 24 to March 29, 2020. The analysis pipeline includes the following steps. After individuating groups of similar or dissimilar regions with respect to the ten types of available COVID-19 data using statistical test, we built several similarity matrices (reported in Supplementary file). Then, we mapped those similarity matrices into networks where nodes represent Italian regions and edges represent similarity relationships (edge length is inversely proportional to similarity). Then, network-based analysis was performed mainly discovering communities of regions that show similar behaviour. Then, network-based analysis was performed by running several community detection algorithms on those networks and by underlying communities of regions that show similar behaviour. The network-based analysis of Italian COVID-19 data is able to elegantly show how regions form communities, i.e. how they join and leave them, along time and how community consistency changes along time and with respect to the different available data.", "qid": 9, "docid": "6n88mcbf", "rank": 99, "score": 6.147500038146973}, {"content": "Title: Risk of a second wave of Covid-19 infections: using artificial intelligence to investigate stringency of physical distancing policies in North America. Content: PURPOSE Accurately forecasting the occurrence of future covid-19-related cases across relaxed (Sweden) and stringent (USA and Canada) policy contexts has a renewed sense of urgency. Moreover, there is a need for a multidimensional county-level approach to monitor the second wave of covid-19 in the USA. METHOD We use an artificial intelligence framework based on timeline of policy interventions that triangulated results based on the three approaches-Bayesian susceptible-infected-recovered (SIR), Kalman filter, and machine learning. RESULTS Our findings suggest three important insights. First, the effective growth rate of covid-19 infections dropped in response to the approximate dates of key policy interventions. We find that the change points for spreading rates approximately coincide with the timelines of policy interventions across respective countries. Second, forecasted trend until mid-June in the USA was downward trending, stable, and linear. Sweden is likely to be heading in the other direction. That is, Sweden's forecasted trend until mid-June appears to be non-linear and upward trending. Canada appears to fall somewhere in the middle-the trend for the same period is flat. Third, a Kalman filter based robustness check indicates that by mid-June the USA will likely have close to two million virus cases, while Sweden will likely have over 44,000 covid-19 cases. CONCLUSION We show that drop in effective growth rate of covid-19 infections was sharper in the case of stringent policies (USA and Canada) but was more gradual in the case of relaxed policy (Sweden). Our study exhorts policy makers to take these results into account as they consider the implications of relaxing lockdown measures.", "qid": 9, "docid": "6ar58ea6", "rank": 100, "score": 6.145100116729736}]}
{"query": "are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19?", "hits": [{"content": "Title: ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective Content: Potential but unconfirmed risk factors for coronavirus disease 2019 (COVID-19) in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, ACE (angiotensin-converting enzyme) inhibitors, and Ang II (angiotensin II) receptor blockers. Coronavirus binding to ACE2 (angiotensin-converting enzyme 2), a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus, but the reasons are unclear. This review will highlight the relationship of COVID-19 with hypertension, use of ACE inhibitors and Ang II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the ACE 2/Ang-(1-7) pathway in children and the clinical evidence for how ACE inhibitors and Ang II receptor blockers affect this important pathway. Given the importance of the ACE 2/Ang-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe COVID-19.", "qid": 20, "docid": "ohj6misb", "rank": 1, "score": 20.208099365234375}, {"content": "Title: Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon Renin-Angiotensin System Blockers Content: During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.", "qid": 20, "docid": "axvti3jw", "rank": 2, "score": 20.13960075378418}, {"content": "Title: Hypertension prevalence in human coronavirus disease: the role of ACE system in infection spread and severity Content: The prevalence of hypertension is high in patients affected by coronavirus disease 2019 (COVID-2019) and it appears to be related to an increased risk of mortality, as shown in many epidemiological studies. The angiotensin-converting enzyme (ACE) system is not uniformly expressed in all of the human races, and current differences could explain some of the geographical discrepancies in infection around the world. Furthermore, animal studies have shown that the ACE2 receptor is a potential pathway for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. As two-thirds of hypertensive patients take ACE inhibitors/angiotensin receptor blockers, several concerns have been raised about the detrimental role of current antihypertensive drugs in COVID-19. This report summarizes the recent evidence for and against the administration of ACE blockade in the COVID-19 era.", "qid": 20, "docid": "ih8oxr40", "rank": 3, "score": 20.082799911499023}, {"content": "Title: The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms Content: There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.", "qid": 20, "docid": "ux844b25", "rank": 4, "score": 20.066200256347656}, {"content": "Title: A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019) Content: There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes We reviewed the available evidence, and have not found this to be the case We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use", "qid": 20, "docid": "53107z56", "rank": 5, "score": 19.743600845336914}, {"content": "Title: A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019). Content: There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes. We reviewed the available evidence, and have not found this to be the case. We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use.", "qid": 20, "docid": "z3l6eden", "rank": 6, "score": 19.74359893798828}, {"content": "Title: Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 Content: Intravenous infusions of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in experimental animals increase the numbers of angiotensin-converting enzyme 2 (ACE2) receptors in the cardiopulmonary circulation. ACE2 receptors serve as binding sites for SARS-CoV-2 virions in the lungs. Patients who take ACEIs and ARBS may be at increased risk of severe disease outcomes due to SARS-CoV-2 infections.", "qid": 20, "docid": "240jc7l4", "rank": 7, "score": 19.69409942626953}, {"content": "Title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? Content: PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. RECENT FINDINGS: In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. SUMMARY: From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.", "qid": 20, "docid": "r426u5dz", "rank": 8, "score": 19.537700653076172}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19 Content: BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving \u22651 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.", "qid": 20, "docid": "roj3om68", "rank": 9, "score": 19.51959991455078}, {"content": "Title: [Hypertension, RAAS blockade and risk in COVID-19 patients]. Content: SARS-coronavirus 2 (SARS-CoV-2) enters the host-cells by binding the transmembraneous angiotensin converting enzyme 2 (ACE2) when causing coronavirus disease 2019 (COVID-19). The role of angiotensin converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) in COVID-19 is debated. Several well-conducted observational studies show no increased risk from RAAS blockade in COVID-19 patients and are detailed in this brief review. The Swedish Society of Hypertension, Stroke and Vascular Medicine supports current recommendations that ongoing RAAS blockade should be maintained in patients with COVID-19.", "qid": 20, "docid": "jyfcpsu6", "rank": 10, "score": 19.341100692749023}, {"content": "Title: Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes Content: Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p\u22640.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.", "qid": 20, "docid": "r8fmq65g", "rank": 11, "score": 19.14940071105957}, {"content": "Title: RAAS inhibitors do not increase the risk of COVID-19 Content: According to five new studies, therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with an increased risk of severe disease or in-hospital death among patients with COVID-19.", "qid": 20, "docid": "nxrg9fi6", "rank": 12, "score": 19.144800186157227}, {"content": "Title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients Content: The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1\u2013angiotensin II\u2013angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2\u2013angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2\u2013angiotensin(1-7)\u2013Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.", "qid": 20, "docid": "6cxndab8", "rank": 13, "score": 19.12969970703125}, {"content": "Title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients Content: The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.", "qid": 20, "docid": "f48gflvs", "rank": 14, "score": 19.129697799682617}, {"content": "Title: A Viewpoint on Angiotensin-Converting Enzyme 2, Anti-Hypertensives and Coronavirus Disease 2019 (COVID-19). Content: TO THE EDITOR, The current life threatening pandemic outbreak of coronavirus disease 2019 (COVID-19) is hitting the whole world in terms of mortality as well as economic losses [1,2]. It has thought to be originated from Wuhan, China, in December 2019. This outbreak has link to Wuhan's seafood and exotic animal wholesale markets [3,4]. As SARS-CoV-2 is highly contagious, it has now spread to each and every corner of the world [1,2]. According to the World Health Organization (WHO) situation report (77th), updated on 6 April, 2020 there have been globally 1210956 confirmed cases and 67 594 deaths of COVID-19 [2]. This viral outbreak has now posed a global threat to healthcare systems. So many, efforts are going on to find new drugs or to repurpose already existed drugs [1,5-7]. Majoritily, it has been found that most of the COVID-19 patients belong to cardiovascular comorbidities [8-10]. It is obvious that they qualify for antihypertensive therapy. Many of them are treating with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB)[8]. There has been considerable debate in scientific community and health professionals about whether angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may increase attractiveness towards the COVID-19 virus infection or not ?[9-16]. One of the important concern highlighted by these studies involving antihypertensive medications suggested that these drugs might cause increments in abundance of SARS-CoV-2 receptor henceforth causing COVID-19 by entering into cells [17,18]. This suggests plausible increase in ACE2 receptors on lung and heart cells and hence offering more entry points for SARS-CoV-2[17]. However, no strong evidence has been noted. There has been more number of commentaries published explaining both sides and still they are appearing on daily basis [12-16]. Herein, we tried to summaries, clinical aspects on ACEs and ARBs based on literature and commentaries to explain both the sides. A recent published article in Nature by Zhou et al. (2020)[19], reported that the angiotensin-converting enzyme II (ACE2) is acting as receptor for SARS Coronavirus 2.This receptors was also acted as receptors for SARS-CoV and HCoV-NL63. Zhou et al. (2020), clearly wrote that \"We show that 2019-nCoV (COVID-19) is able to use ACE2 proteins as an entry receptor to enter ACE2-expressing cells, but not cells that did not express ACE2, indicating that ACE2 is probably the cell receptor through which 2019-nCoV enters cells\". ACE2 is aminopeptidase responsible for cleaving angiotensin I and angiotensin II into the angiotensin-(1-9) and angiotensin-(1-7) peptides[20]. Normally, ACE2 have been found to be overexpressed in clinical conditions including heart failure, arterial hypertension, etc. It has also been noted that ACE2 acts as a functional receptor for SARS-CoV-2 entry. There have been several literatures supporting the role of a cardiovascular-protective ACE2-angiotensin-(1-7)-Mas receptor axis. Recent viewpoint article published in JAMA journal by author Majd AlGhatrif exaplains[15] correlations among aging, cardiovascular diseases and COVID-19 patients. He clearly concluded important fact saying, \"compared with young individuals, older persons with cardiovascular disorders (CVD); who already have reduced ACE2 levels will be expected to be more predisposed to exaggerated inflammation with further reduction in ACE2 expression in the context of COVID-19, manifesting with greater disease severity\". One of well-known Austrian scientist Prof. Josef Penninger[21], Josef Penninger noted important relationship between RAS (the renin-angiotensin system) and ACE2. He is particularly focusing on ACE2 as a potential treatment approach. In one of the article by Mourad et al., (2020), explained different effects on ACE2 levels in correlation with different administrations of RAAS inhibitors and believed that chronic treatment with ACE inhibitors has no reason to influence the course of SARS-CoV-2 infection[22]. A reply to this article has also been published by Zheng et al., (2020)[23] saying that \"although ACE2 has been identified as the functional receptor for SARS-CoV-2, the role of ACE2 in the progression of COVID-19 after SARS-CoV-2 infection is still controversial, so the benefits of aliskiren use in patients with COVID-19 needs further investigation\". Today, many healthcare societies' especially cardiovascular societies are urging the patients suffering from CVDs (cardiovascular diseases) not to discontinue their medications[24-26]. These healthcare societies give more stress upon statement saying that there is no sound evidence to correlate ACEs and ARBs leading risk of COVID-19 infection. It has also been noted that healthcare societies do not suggest immediate starting of ACEIs/ARBs in those patients having no settlements with clinical conditions like heart failure, diabetes, hypertension, etc. As these statements adheres to current state of evidences. The same conclusion has been derived from the recent article by Ankit Patel et al., (2020)[24]. This article suggested that there has been no definitive evidence to suggest ACE inhibitors and ARBs worsening of COVID-19. A study published by Vaduganathan et al., (2020) in New England Journal of Medicine discussed the uncertain effects of RAAS blockers on ACE2 levels[27]. They also derived to conclusion that ACE2 may be beneficial in COVID-19 patients with lung injury. This team also suggests that withdrawal of RAAS inhibitors may be harmful. A very recent review published by Dr. Sanchis-Gomar and his co-authors in Mayo Clinic Proceedings[14], by analysing more than 60 articles, concluded the fact that \"no studies have reported an increase in circulating ACE2 levels or expression thus far, and increased expression would not necessarily imply an increased risk of infection or disease severity\". Dr. Sanchis-Gomar, studies both articles explaining that elevated levels of angiotensin II fostering acute respiratory distress syndrome (ARDS) as well as significance of RAAS inhibitors in therapy in treating patients with COVID-19. However, authors noted that more research in this regard is needed. CONCLUSION In this regards, more laboratory and clinical evidences are required in order to decide COVID-19 treatment. In conclusion to this debate, suggesting roles of antihypertensive agents and severity leading changes in ACE2 levels, may shed more light on infectivity and outcome of COVID-19.There is an urgent need to establish whether treatments with antihypertensive (ACEI's/ ARBs) needs to be determined.", "qid": 20, "docid": "0x02bmti", "rank": 15, "score": 18.958099365234375}, {"content": "Title: Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin\u2013angiotensin\u2013aldosterone inhibitors Content: AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort). The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = \u20130.17, P = 0.002) and ARB use (estimate = \u20130.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.", "qid": 20, "docid": "4hz2yyl5", "rank": 16, "score": 18.89590072631836}, {"content": "Title: Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors Content: AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.", "qid": 20, "docid": "8d6xxjgu", "rank": 17, "score": 18.895898818969727}, {"content": "Title: ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective. Content: Potential but unconfirmed risk factors for coronavirus disease 2019 in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Coronavirus binding to angiotensin-converting enzyme 2, a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus but the reasons are unclear. This review will highlight the relationship of coronavirus disease 2019 with hypertension, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway in children and the clinical evidence for how angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers affect this important pathway. Given the importance of the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe coronavirus disease 2019.", "qid": 20, "docid": "uu1jml2c", "rank": 18, "score": 18.77039909362793}, {"content": "Title: Treatment of patients with COVID-19 and concomitant cardiovascular diseases: Do not Forget about the Principles of Evidence-based Medicine/ \u041b\u0435\u0447\u0435\u043d\u0438\u0435 \u0431\u043e\u043b\u044c\u043d\u044b\u0445 \u0441 COVID-19 \u0438 \u0441\u043e\u043f\u0443\u0442\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u043c\u0438 \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u043e\u0441\u0443\u0434\u0438\u0441\u0442\u044b\u043c\u0438 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f\u043c\u0438: \u043d\u0435 \u0437\u0430\u0431\u044b\u0432\u0430\u0442\u044c \u043e \u043f\u0440\u0438\u043d\u0446\u0438\u043f\u0430\u0445 \u0434\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044c\u043d\u043e\u0439 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u044b Content: The recent discussion about the dangers of using angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA) in patients with COVID-19 is analyzed in the article. There is controversy over the hypothesis that these drugs can be factors contributing to an unfavorable outcome of a viral disease, as well as the absence of any clinical evidence for this hypothesis. The opinion that withdrawal of ACE inhibitors and ARA in patients with COVID-19 may increase the risk of adverse outcomes is presented.", "qid": 20, "docid": "i7scw9mu", "rank": 19, "score": 18.720199584960938}, {"content": "Title: Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study Content: With the capability of inducing elevated expression of ACE2 (angiotensin-converting enzyme 2), the cellular receptor for severe acute respiratory syndrome coronavirus 2, angiotensin II receptor blockers (ARBs) or ACE inhibitors treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACE inhibitors on coronavirus disease 2019 (COVID-19) in a retrospective, single-center study. One hundred twenty-six patients with COVID-19 and preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine in Wuhan from January 5 to February 22, 2020, were retrospectively allocated to ARBs/ACE inhibitors group (n=43) and non-ARBs/ACE inhibitors group (n=83) according to their antihypertensive medication. One hundred twenty-five age- and sex-matched patients with COVID-19 without hypertension were randomly selected as nonhypertension controls. In addition, the medication history of 1942 patients with hypertension that were admitted to Hubei Provincial Hospital of Traditional Chinese Medicine from November 1 to December 31, 2019, before the COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical, and laboratory data were collected, analyzed, and compared between these groups. The frequency of ARBs/ACE inhibitors usage in patients with hypertension with or without COVID-19 were comparable. Among patients with COVID-19 and hypertension, those received either ARBs/ACE inhibitors or non-ARBs/ACE inhibitors had comparable blood pressure. However, ARBs/ACE inhibitors group had significantly lower concentrations of hs-CRP (high-sensitivity C-reactive protein; P=0.049) and PCT (procalcitonin, P=0.008). Furthermore, a lower proportion of critical patients (9.3% versus 22.9%; P=0.061) and a lower death rate (4.7% versus 13.3%; P=0.216) were observed in ARBs/ACE inhibitors group than non-ARBs/ACE inhibitors group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACE inhibitors in patients with COVID-19 and preexisting hypertension.", "qid": 20, "docid": "bwfrjrr9", "rank": 20, "score": 18.71940040588379}, {"content": "Title: A systematic review to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers Content: Introduction: Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor upregulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence but there is need for an updated systematic review of latest clinical studies. Methods: A search was conducted on PubMed, Google Scholar, EMBASE and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEI and/or ARB. Results: A total of eight studies were included in the review. There were conflicting findings reported in several studies as Meng J. et al, Liu Y. et al and Feng Y. reported that patients on ACE inhibitors/ARB had lower rates of severe outcomes whereas Richardson S. et al reported higher rates of invasive ventilation and intensive care unit (ICU) admissions in patients on ACE inhibitors/ARB as compared to non-users. However, Zhang P. et al found slightly higher rates of ICU admissions in patients on ACE inhibitors and ARB as compared to non-users. Similarly, there were conflicting results in the rate of mortality reported by the various clinical studies as well. Meng J. et al, Li J. et al and Zhang P. et al reported lower rates of mortality in ACE inhibitors/ARB users versus non-users whereas Guo J. et al reported higher rates of mortality in patients on ACE inhibitors/ARB as compared to non-users. Additionally, a large study conducted in New York by Richardson S. et al raised concerns with worse mortality outcomes in patients on ACEI/ ARB. Conclusion: It is concluded that ACEI and ARB should be continued in COVID-19 patients, albeit while exercising caution until larger clinical studies and randomized controlled trials confirm their safety. Additionally, the individual patient factors like ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "a0asoy8j", "rank": 21, "score": 18.595800399780273}, {"content": "Title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies Content: SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation. Those effects, together with the \u201ccytokine storm\u201d are involved in a worse prognosis. In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host\u2019s cells and tissues. By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases. Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme. Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients? Do they act on multiple cell types? Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes. At present, insufficient detailed data from trials have been made available.", "qid": 20, "docid": "6w13xo2a", "rank": 22, "score": 18.442699432373047}, {"content": "Title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies Content: SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation. Those effects, together with the \"cytokine storm\" are involved in a worse prognosis. In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host's cells and tissues. By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases. Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme. Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients? Do they act on multiple cell types? Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes. At present, insufficient detailed data from trials have been made available.", "qid": 20, "docid": "ppo3ryi5", "rank": 23, "score": 18.442697525024414}, {"content": "Title: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust Content: AIMS: The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 \u00b1 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.", "qid": 20, "docid": "aj1yup6a", "rank": 24, "score": 18.420499801635742}, {"content": "Title: Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement Content: Since the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has emerged from China, the infection (novel corona virus disease-2019, COVID-19) has affected many countries and led to many deaths worldwide. Like SARS-CoV, angiotencin converting enzyme (ACE)2 as a functional receptor for SARS-CoV2 is essential for the virus to make an entry into the cell. ACE2 is a part of Renin-Angiotensin-Aldosterone System, which is expressed in several organs that opposes the angiotensin (Ang) II functions by converting Ang II to Ang (1-7), the one with vasodilation effects. The death rate of COVID-19 is estimated to be approximately 3.4%; however, some comorbid conditions like underlying cardiovascular disease, hypertension, and diabetes increase the risk of mortality. In addition, cardiovascular involvement as a complication of SARS-CoV2 could be direct through either ACE2 receptors that are expressed tremendously in the heart, or by the surge of different cytokines or by acute respiratory distress syndrome-induced hypoxia. Traditional risk factors could aggravate the process of COVID-19 infection that urges the triage of these high-risk patients for SARS-CoV2. Currently, there is no effective, proven treatment or vaccination for COVID-19, but many investigators are struggling to find a treatment strategy as soon as possible. Some potential medications like chloroquine by itself or in combination with azithromycin and some protease inhibitors used for the treatment of COVID-19 have cardiovascular adverse effects, which should be kept in mind while the patients taking these medications are being closely monitored.", "qid": 20, "docid": "7gasxvwd", "rank": 25, "score": 18.415300369262695}, {"content": "Title: Renin-angiotensin system inhibition in COVID-19 patients Content: Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type\u00ad1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV\u00ad2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "qid": 20, "docid": "3l1nru0l", "rank": 26, "score": 18.388500213623047}, {"content": "Title: Renin-angiotensin system inhibition in COVID-19 patients Content: Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type\u20111 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV\u20112 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "qid": 20, "docid": "d9wfmvp8", "rank": 27, "score": 18.24650001525879}, {"content": "Title: Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients Content: Summary Background The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. Methods In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. Findings Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0.343, 95% CI 0.128-0.916, p=0.025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. Interpretation Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences", "qid": 20, "docid": "o0ot59di", "rank": 28, "score": 18.227699279785156}, {"content": "Title: Renin\u2013Angiotensin\u2013Aldosterone System Blockers and the Risk of Covid-19 Content: BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting\u2013enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case\u2013control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients\u2019 clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (\u00b1SD) age was 68\u00b113 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "qid": 20, "docid": "1pahpghb", "rank": 29, "score": 18.22170066833496}, {"content": "Title: Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19 Content: BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (\u00b1SD) age was 68\u00b113 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "qid": 20, "docid": "3twud97m", "rank": 30, "score": 18.221698760986328}, {"content": "Title: Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities Content: The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells. Thus, some health care providers and media sources have questioned the continued use of ACE inhibitors and ARBs. In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin-angiotensin-aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors. We propose that the application of RAAS inhibitors for COVID-19 patients with CVDs may be beneficial rather than harmful.", "qid": 20, "docid": "795u01zb", "rank": 31, "score": 18.132200241088867}, {"content": "Title: Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities Content: The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells. Thus, some health care providers and media sources have questioned the continued use of ACE inhibitors and ARBs. In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin\u2013angiotensin\u2013aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors. We propose that the application of RAAS inhibitors for COVID-19 patients with CVDs may be beneficial rather than harmful.", "qid": 20, "docid": "za4x9igf", "rank": 32, "score": 18.132198333740234}, {"content": "Title: Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study Content: INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged \u2265 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer\u2019s dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.", "qid": 20, "docid": "2530zdeq", "rank": 33, "score": 18.10569953918457}, {"content": "Title: Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study Content: INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged &#8805; 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer's dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.", "qid": 20, "docid": "z5uf591v", "rank": 34, "score": 18.105697631835938}, {"content": "Title: Angiotensin II Receptors \u2010 Impact for COVID\u201019 Severity Content: COVID\u201019 is an outbreak of viral pneumonia which became a global health crisis, and the risk of morbidity and mortality of people with obesity are higher. SARS\u2010CoV\u20102, the pathogen of COVID\u201019, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog\u20102 (ACE2). ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE\u2010Ang\u2010II\u2010AT1R axis and ACE2\u2010Ang 1\u20107\u2010Mas axis. Viral entry process eventuate in downregulation of ACE2 and subsequent activation of ACE\u2010Ang\u2010II\u2010AT1R axis. ACE\u2010Ang II\u2010AT1R axis increases lipid storage, reduces white\u2010to\u2010beige fat conversion and plays role in obesity. Conversely, adipose tissue is an important source of angiotensin, and obesity results in increased systemic RAS. ACE\u2010Ang\u2010II\u2010AT1R axis, which has proinflammatory, profibrotic, prothrombotic and vasoconstrictive effects, is potential mechanism of more severe SARS\u2010CoV\u20102 infection. The link between obesity and severe COVID\u201019 may be attributed to ACE2 consumption and subsequent ACE\u2010Ang\u2010II\u2010AT1R axis activation. Therefore, patients with SARS\u2010CoV\u20102 infection may benefit from therapeutic strategies that activate ACE2\u2010Ang 1\u20107\u2010Mas axis, such as Ang II reseptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2. This article is protected by copyright. All rights reserved.", "qid": 20, "docid": "bsz7ezzi", "rank": 35, "score": 18.028499603271484}, {"content": "Title: Angiotensin II Receptors - Impact for COVID-19 Severity Content: COVID-19 is an outbreak of viral pneumonia which became a global health crisis, and the risk of morbidity and mortality of people with obesity are higher. SARS-CoV-2, the pathogen of COVID-19, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog-2 (ACE2). ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE-Ang-II-AT1R axis and ACE2-Ang 1-7-Mas axis. Viral entry process eventuate in downregulation of ACE2 and subsequent activation of ACE-Ang-II-AT1R axis. ACE-Ang II-AT1R axis increases lipid storage, reduces white-to-beige fat conversion and plays role in obesity. Conversely, adipose tissue is an important source of angiotensin, and obesity results in increased systemic RAS. ACE-Ang-II-AT1R axis, which has proinflammatory, profibrotic, prothrombotic and vasoconstrictive effects, is potential mechanism of more severe SARS-CoV-2 infection. The link between obesity and severe COVID-19 may be attributed to ACE2 consumption and subsequent ACE-Ang-II-AT1R axis activation. Therefore, patients with SARS-CoV-2 infection may benefit from therapeutic strategies that activate ACE2-Ang 1-7-Mas axis, such as Ang II reseptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2. This article is protected by copyright. All rights reserved.", "qid": 20, "docid": "qrsqk2fc", "rank": 36, "score": 18.02849769592285}, {"content": "Title: Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: \u00bfAumentan el riesgo de padecer COVID-19? Content: Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "qid": 20, "docid": "ynias4ga", "rank": 37, "score": 18.0226993560791}, {"content": "Title: Diabetes and COVID-19: evidence, current status and unanswered research questions. Content: Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.", "qid": 20, "docid": "4ti8l2ea", "rank": 38, "score": 17.984899520874023}, {"content": "Title: Diabetes and COVID-19: evidence, current status and unanswered research questions Content: Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.", "qid": 20, "docid": "sjcadz5j", "rank": 39, "score": 17.98489761352539}, {"content": "Title: Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 20, "docid": "fskfnmig", "rank": 40, "score": 17.85650062561035}, {"content": "Title: Renin\u2013Angiotensin\u2013Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin\u2013angiotensin\u2013aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 20, "docid": "oapjfamm", "rank": 41, "score": 17.85649871826172}, {"content": "Title: Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic. Content: COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "qid": 20, "docid": "vv9ssqb8", "rank": 42, "score": 17.854299545288086}, {"content": "Title: Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic Content: COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "qid": 20, "docid": "wumtwdi5", "rank": 43, "score": 17.854297637939453}, {"content": "Title: COVID 19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Content: Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID\u201019) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID\u201019 with higher percentages, 25%\u201335% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by the exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID\u201019. A key role may be that of the renin\u2013angiotensin\u2010aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infects human cells binding to angiotensin\u2010converting\u2010enzyme 2 (ACE2), an enzyme responsible of the cleavage of angiotensin II into angiotensin 1\u20137, which has vasodilating and anti\u2010inflammatory effects. Virus\u2010mediated downregulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper\u2010inflammatory reaction of COVID\u201019. On the other hand, ACE2 may be upregulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 upregulation may increase the susceptibility to COVID\u201019 but may be also protective versus angiotensin II mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID\u201019 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects. This article is protected by copyright. All rights reserved.", "qid": 20, "docid": "17hyh3n5", "rank": 44, "score": 17.852699279785156}, {"content": "Title: COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Content: Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.", "qid": 20, "docid": "5svfhlzh", "rank": 45, "score": 17.852697372436523}, {"content": "Title: Angiotensin\u2010converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor Content: Angiotensin\u2010converting enzyme 2 (ACE2) is thought to act in an opposing manner to its homologue, angiotensin\u2010converting enzyme (ACE), by inactivating the vasoconstrictor peptide angiotensin II and generating the vasodilatory fragment, angiotensin(1\u20137). Both ACE and ACE2 are membrane\u2010bound ectoenzymes and may circulate in plasma as a consequence of a proteolytic shedding event. In this study, we show that ACE2 circulates in human plasma, but its activity is suppressed by the presence of an endogenous inhibitor. Partial purification of this inhibitor indicated that the inhibitor is small, hydrophilic and cationic, but not a divalent metal cation. These observations led us to develop a method for removal of the inhibitor, thus allowing detection of plasma ACE2 levels using a sensitive quenched fluorescent substrate\u2010based assay. Using this technique, ACE2 activity measured in plasma from healthy volunteers (n= 18) ranged from 1.31 to 8.69 pmol substrate cleaved min(\u22121) ml(\u22121) (mean \u00b1s.e.m., 4.44 \u00b1 0.56 pmol min(\u22121) ml(\u22121)). Future studies of patients with cardiovascular, renal and liver disease will determine whether plasma ACE2 is elevated in parallel with increased tissue levels observed in these conditions.", "qid": 20, "docid": "rq94lma3", "rank": 46, "score": 17.678600311279297}, {"content": "Title: Relationship between ACE-inhibitors, ARBs and SARS-CoV-2 infection: where are we? Content: SARS-CoV-2 is spreading rapidly all over the world. The case fatality rate seems higher in cardiovascular disease and hypertension. Other comorbidities do not seem to confer the same risk, therefore the understanding of the relationship between infection and cardiovascular system could be a crucial point for the fight against the virus. A great interest is currently directed towards the angiotensin 2 converting enzyme (ACE 2) which is the SARS-CoV-2 receptor and creates important connections between the virus replication pathway, the cardiovascular system and blood pressure. All cardiovascular conditions share an imbalance of the renin angiotensin system (RAAS) in which ACE 2 plays a central role. In the last few days, much confusion has appeared about the management of therapy with angiotensin converting enzyme inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) in infected patients and in those at risk of critical illness in case of infection. In this article we will try to reorder the major opinions currently emerging on this topic.", "qid": 20, "docid": "43th3c20", "rank": 47, "score": 17.66469955444336}, {"content": "Title: Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis. Content: Background The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19. Methods Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19. Results 22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0). Conclusion This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents. Keywords: COVID-19; Angiotensin-converting enzyme inhibitor; Angiotensin-receptor blockers; risk; systematic review; meta-analysis", "qid": 20, "docid": "7necpu7c", "rank": 48, "score": 17.506999969482422}, {"content": "Title: [Role of age, comorbidity and renin- angiotensin-aldosterone system in COVID-19. Effects of ACE inhibitors and angiotensin receptor blockers]. Content: The review addressed the relationship of coronavirus disease 2019 (COVID-19) with functioning of the renin-angiotensin-aldosterone axis and the causes for unfavorable prognosis depending on patients' age and comorbidities. The authors discussed in detail potential effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on the risk of infection and the course of COVID-2019 as well as the effect of SARS-COV2 virus on the cardiovascular system.", "qid": 20, "docid": "04h53wjz", "rank": 49, "score": 17.499900817871094}, {"content": "Title: [Role of age, comorbidity and renin- angiotensin-aldosterone system in COVID-19. Effects of ACE inhibitors and angiotensin receptor blockers] Content: The review addressed the relationship of coronavirus disease 2019 (COVID-19) with functioning of the renin-angiotensin-aldosterone axis and the causes for unfavorable prognosis depending on patients' age and comorbidities. The authors discussed in detail potential effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on the risk of infection and the course of COVID-2019 as well as the effect of SARS-COV2 virus on the cardiovascular system.", "qid": 20, "docid": "8nn7lja8", "rank": 50, "score": 17.49989891052246}, {"content": "Title: SARS-CoV2: should inhibitors of the renin\u2013angiotensin system be withdrawn in patients with COVID-19? ;European Heart Journal ;Oxford Academic Content: In a rapid response published online by the British Medical Journal, Sommerstein and Gr\u00e4ni1 pushed forward the hypothesis that angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) could act as a potential risk factor for fatal Corona virus disease 2019 (COVID-19) by up-regulating ACE2 This notion was quickly picked up by the lay press and sparked concerns among physicians and patients regarding the intake of inhibitors of the renin\u2013angiotensin\u2013aldosterone system (RAAS) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infected individuals 1 In this article, we try to shed light on what is known and unknown regarding the RAAS and SARS-CoV2 interaction We find translational evidence for diverse roles of the RAAS, which allows to formulate also the opposite hypothesis, i e that inhibition of the RAAS might be protective in COVID-19 [Truncated]", "qid": 20, "docid": "vzwsgfn9", "rank": 51, "score": 17.475799560546875}, {"content": "Title: Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease Content: BACKGROUND: Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3\u20135 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. METHODS: Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. RESULTS: In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. CONCLUSIONS: Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event.", "qid": 20, "docid": "nxx22lcu", "rank": 52, "score": 17.41950035095215}, {"content": "Title: Ramipril in High Risk Patients with COVID-19 Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). This interaction has been proposed as a potential risk factor in patients treated with RAAS-inhibitors. OBJECTIVES: To analyze if RAAS-inhibitors modify the risk for COVID-19. METHODS: RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain. We performed a non-pre-specified interim analysis to evaluate its impact on COVID-19 risk in this vulnerable population. RESULTS: As in April 1st 2020, 102 patients (50 Ramipril and 52 controls) were included in the trial. Mean age was 82.3\u00b16.1 years, 56.9% males. Median time of Ramipril treatment was 6 months [IQR:2.9-11.4]. Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving Ramipril, HR=1.150 [95%CI: 0.351-3.768]). The risk of COVID-19 was increased in older patients (p=0.019), those with atrial fibrillation (p=0.066), lower hematocrit (p=0.084), and more comorbidities according to Society of thoracic surgeons score (p=0.065). Admission and oxygen supply was required in 4.9% (2 patients in the Ramipril and 3 in control), and 4 of them died (two in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p=0.039). CONCLUSIONS: In a high risk population of old patients with cardiovascular disease, randomization to Ramipril had no impact in the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS-inhibitor treatment during COVID-19 crisis.", "qid": 20, "docid": "67psg92z", "rank": 53, "score": 17.2007999420166}, {"content": "Title: Ramipril in High Risk Patients with COVID-19 Content: Abstract Background The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). This interaction has been proposed as a potential risk factor in patients treated with RAAS-inhibitors. Objectives To analyze if RAAS-inhibitors modify the risk for COVID-19. Methods RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain. We performed a non-pre-specified interim analysis to evaluate its impact on COVID-19 risk in this vulnerable population. Results As in April 1st 2020, 102 patients (50 Ramipril and 52 controls) were included in the trial. Mean age was 82.3\u00b16.1 years, 56.9% males. Median time of Ramipril treatment was 6 months [IQR:2.9-11.4]. Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving Ramipril, HR=1.150 [95%CI: 0.351-3.768]). The risk of COVID-19 was increased in older patients (p=0.019), those with atrial fibrillation (p=0.066), lower hematocrit (p=0.084), and more comorbidities according to Society of thoracic surgeons score (p=0.065). Admission and oxygen supply was required in 4.9% (2 patients in the Ramipril and 3 in control), and 4 of them died (two in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p=0.039). Conclusions In a high risk population of old patients with cardiovascular disease, randomization to Ramipril had no impact in the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS-inhibitor treatment during COVID-19 crisis.", "qid": 20, "docid": "uxv06hen", "rank": 54, "score": 17.20079803466797}, {"content": "Title: Modeling the molecular impact of the SARS-CoV-2 infection on the renin-angiotensin system Content: Infection by the SARS-CoV-2 virus is mediated by the binding of its spike protein to the membrane-bound angiotensin converting enzyme 2 (ACE2), which plays a pivotal role in the renin-angiotensin system (RAS). The understanding of RAS dysregulation due to this viral infection is of fundamental importance to better understand the pathogenic mechanisms and risk factors of the coronavirus disease COVID-19, and to design effective therapeutic strategies. To address this issue, we built a mathematical model of RAS based on data about protein and peptide concentrations in normotensive and hypertensive individuals. We first tested our model on clinical data on the action of antihypertensive RAS-blocking drugs in control individuals. Despite the simplicity of our model, it reproduces very well, without any fitting of additional parameters, the impact of a series of drugs, i.e. angiotensin-converting enzyme inhibitors (ACE-I), direct renin inhibitors (DRI) and angiotensin II receptor blockers (ARB). We applied our model to analyze the impact of SARS-CoV-2 infection on the RAS system, which we modeled through a downregulation of ACE2 related to viral load. Moreover, we analyzed the effect of RAS-blockers and other RAS-targeting drugs, i.e. human recombinant ACE2 (rhACE2) and angiotensin 1-7 peptide (Ang1-7), on the RAS system of normotensive and hypertensive COVID-19 patients. We found that while ACE-I, DRI, rhACE2 and Ang1-7 tend to improve the clinical outcomes in a tension-dependent manner, the use of ARB appears to worsen it. The mathematical model that we developed offers the interesting possibility of testing in silico the RAS dysregulation upon SARS-CoV-2 infection and of predicting how risk factors as well as different drugs, alone or in combination, impact on RAS and disease severity.", "qid": 20, "docid": "ble3xfa3", "rank": 55, "score": 17.197500228881836}, {"content": "Title: Identification of angiotensin converting enzyme 2 in the rodent retina. Content: PURPOSE An active renin-angiotensin system has been found in the retina of rats and humans. Angiotensin-converting enzyme 2 (ACE2) is a recently discovered enzymatic homologue of Angiotensin-converting enzyme (ACE) that may be an important new component of the renin-angiotensin system (RAS). This study assesses the involvement of ACE2 in the normal and diabetic rodent retina and its modulation by ACE inhibition. METHODS Sprague-Dawley rats were randomised into three groups, control, diabetes, and diabetes plus ramipril, with diabetes induced with the cell toxin streptozocin and the study run for 24 weeks. ACE2 and ACE gene levels were measured using quantitative real-time polymerase chain reaction (QRT-PCR), ACE2 protein expression was confirmed by Western blotting, and ACE and ACE2 catalytic activity were measured using specific activity assays in the rat retina. Localisation of ACE2 mRNA and protein were determined by in situ hybridisation and immunohistochemistry, respectively. RESULTS ACE mRNA levels were decreased to approximately 50% in the diabetic retina, but ACE2 mRNA levels were not significantly changed. ACE but not ACE2 gene expression was influenced by ramipril treatment. Following immunostaining, both ACE2 and ACE protein were localised predominantly to the inner nuclear layer (INL) but also to photoreceptors. In the diabetic retina, ACE enzyme activity was decreased, whereas ACE2 enzyme activity was increased. CONCLUSIONS This study has identified ACE2 gene and catalytically active protein in the rodent retina. In diabetes, the major changes were a decrease in ACE but an increase in ACE2 enzymatic activity. The ACE inhibitor ramipril did not reduce ACE2 enzymatic activity.", "qid": 20, "docid": "ufvn688w", "rank": 56, "score": 17.194799423217773}, {"content": "Title: Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study Content: INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. METHODS: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. RESULTS: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 \u2013 1.14), nor any difference for mono/combination use (1.01; 0.90 \u2013 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 \u2013 1.05) and marginally significant for mono/combination users (0.88; 0.79 \u2013 0.99). We observed, however, no significant difference between drug-classes for COVID-19 hospitalization or pneumonia risk across all comparisons. CONCLUSION: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.", "qid": 20, "docid": "7jzsj3xl", "rank": 57, "score": 17.166400909423828}, {"content": "Title: The role of angiotensin-converting enzyme 2 in the pathogenesis of COVID-19: the villain or the hero? Content: Angiotensin-converting enzyme 2 (ACE 2) is the entry receptor for the novel coronavirus SARS-CoV-2, the aetiological agent of COVID-19. At the same time, ACE 2 expression decreases during COVID-19. Two seemingly contradictory relationships between the expression of ACE 2 and COVID-19 have been reported. Increased level of expression of ACE 2 may be a risk factor for the development of COVID-19 infection, while reduced ACE 2 expression during COVID-19 leads to acute respiratory distress syndrome. This article provides a comprehensive overview of available scientific knowledge about the role of ACE 2 in the pathogenesis of COVID-19, which is available up to current day. Also, it discusses unknown factors that we will have to reveal in order to understand the whole role of ACE 2 in the pathogenesis of COVID-19.", "qid": 20, "docid": "y94y4v58", "rank": 58, "score": 17.159000396728516}, {"content": "Title: Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome Content: BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1\u20137. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. METHODS: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. RESULTS: Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). CONCLUSION: These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.", "qid": 20, "docid": "ijbrhsl7", "rank": 59, "score": 17.136499404907227}, {"content": "Title: Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19 Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown. METHODS: A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of &#8805;14 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age &#8805;18 years) with COVID-19 admitted to the Istanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated. RESULTS: In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57\u00b115 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27-1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15-0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem). CONCLUSION: Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.", "qid": 20, "docid": "3qs8mnf1", "rank": 60, "score": 17.120500564575195}, {"content": "Title: Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown. METHODS A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of \u226514 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age \u226518 years) with COVID-19 admitted to the \u0130stanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated. RESULTS In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57\u00b115 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27-1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15-0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem). CONCLUSION Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.", "qid": 20, "docid": "z82u8dik", "rank": 61, "score": 17.120498657226562}, {"content": "Title: The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis Content: Background: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. Methods: We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Findings: Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB. Interpretation: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death. Funding Source: None", "qid": 20, "docid": "dwcu6vyp", "rank": 62, "score": 17.0841007232666}, {"content": "Title: Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019 Content: Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "qid": 20, "docid": "7lonkj5p", "rank": 63, "score": 17.072999954223633}, {"content": "Title: Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "qid": 20, "docid": "kxtxzt9f", "rank": 64, "score": 17.072998046875}, {"content": "Title: Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation Content: Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE(2) has been discovered. Both ACE and ACE(2) are emerging as key enzymes of the RAS, where ACE(2) may play a role as negative regulator of ACE. Moreover, ACE(2) appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE(2), and their substrates and by-products are presently still unclear. ACE-inhibitors reduce angiotensin II formation and bradykinin degradation, but do not inhibit ACE(2) activity. Moreover, ACE-inhibitors differ in their affinity for tissue ACE, and it has been suggested that tissue ACE affinity might be responsible for some of the beneficial properties of these drugs. ACE-inhibitors also increase nitric oxide availability, and activate several kinases that may regulate protein synthesis by interacting with the nucleus of the cells (outside-in signaling). The outside-in signaling may also be activated by bradykinin itself. Although, the precise significance of the outside-in signaling is still unclear, this new role of ACE-inhibitors may represent a discriminant factor versus angiotensin II receptors antagonists. This mini review will summarize some new aspects concerning the recently discovered biological functions of RAS and in particular of ACE, ACE(2) and ACE-inhibitors in cardiovascular system.", "qid": 20, "docid": "6xlb7bfa", "rank": 65, "score": 17.069299697875977}, {"content": "Title: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 Content: BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those &#8804;65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.).", "qid": 20, "docid": "4rgwfmht", "rank": 66, "score": 17.014999389648438}, {"content": "Title: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 Content: BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting\u2013enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those \u226465 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women\u2019s Hospital.)", "qid": 20, "docid": "h1mo3bs8", "rank": 67, "score": 17.014997482299805}, {"content": "Title: Brain angiotensin\u2010converting enzymes: role of angiotensin\u2010converting enzyme 2 in processing angiotensin II in mice Content: Angiotensin (Ang)\u2010converting enzyme 2 (ACE2) metabolizes Ang II to the vasodilatory peptide Ang(1\u20137), while neprilysin (NEP) generates Ang(1\u20137) from Ang I. Experiments used novel Surface Enhanced Laser Desorption Ionization\u2010Time of Flight (SELDI\u2010TOF) mass spectroscopic (MS) assays to study Ang processing. Mass spectroscopy was used to measure proteolytic conversion of Ang peptide substrates to their specific peptide products. We compared ACE/ACE2 activity in plasma, brain and kidney from C57BL/6 and NEP (\u2212/\u2212) mice. Plasma or tissue extracts were incubated with Ang I or Ang II (1296 or 1045, m/z, respectively), and generated peptides were monitored with MS. Angiotensin\u2010converting enzyme 2 activity was detected in kidney and brain, but not in plasma. Brain ACE2 activity was highest in hypothalamus. Angiotensin\u2010converting enzyme 2 activity was inhibited by the specific ACE2 inhibitor, DX600 (10 \u03bcm, 99% inhibition), but not by the ACE inhibitor, captopril (10 \u03bcm). Both MS and colorimetric assays showed high ACE activity in plasma and kidney with low levels in brain. To extend these findings, ACE measurements were made in ACE overexpressing mice. Angiotensin\u2010converting enzyme four\u2010copy mice showed higher ACE activity in kidney and plasma with low levels in hypothalamus. In hypothalamus from NEP (\u2212/\u2212) mice, generation of Ang(1\u20137) from Ang I was decreased, suggesting a role for NEP in Ang metabolism. With Ang II as substrate, there was no difference between NEP (\u2212/\u2212) and wild\u2010type control mice, indicating that other enzymes may contribute to generation of Ang(1\u20137). The data suggest a predominant role of hypothalamic ACE2 in the processing of Ang II, in contrast to ACE, which is most active in plasma.", "qid": 20, "docid": "7tg62meg", "rank": 68, "score": 17.001100540161133}, {"content": "Title: The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study Content: Background: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use is associated with the rate of Covid-19 confirmed cases and deaths. Methods: We conducted a geospatial study using publicly available county-level data. The Medicare ACEIs and ARBs prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population. Results: The ACEI use had no effect on Covid-19 confirmed case rate. An average ACEIs use (compared to no-use) was associated with a higher Covid-19 death rate by 1.1 (95%CI 0.4-1.8)%. If the use of ACEIs increases by 0.5% for all counties, the Covid-19 death rate will drop by 0.4% to 0.7(95%CI 0.3-1.1)%; P<0.0001. An average ARBs use (compared to no-use) was associated with a higher Covid-19 confirmed case rate (by 4.2; 95%CI 4.1-4.3 %) and death rate (by 1.1; 95%CI 0.7-1.5 %). Each percent increase in ARBs use was associated with an increase in confirmed case rate by 0.2(0.03-0.4)% and death rate by 0.14(0.08-0.21)%. Conclusions: ARBs, but not ACEIs use rate, is associated with Covid-19 confirmed case rate.", "qid": 20, "docid": "34uorjgw", "rank": 69, "score": 16.99850082397461}, {"content": "Title: Structure and Function of Angiotensin Converting Enzyme and Its Inhibitors Content: Abstract Angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II by removing the two C-terminal amino acids. ACE is well known to be a key part of the rennin-angiotensin system that regulates blood pressure. The inhibitors of ACE have the potency of treating hypertension. This article reviews the structure-function relationship of ACE as well as its gene polymorphism and inhibitor development. In particular, it has been found that the catalytic mechanisms of the two active sites of somatic ACE in the cleavage of angiotensin I and bradykin are different. Therefore, by specifically targeting the individual active sites of somatic ACE, it will likely offer a new way to develop novel ACE inhibitors with fewer side effects.", "qid": 20, "docid": "hui5jaiu", "rank": 70, "score": 16.962799072265625}, {"content": "Title: Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced lung injury by regulating the balance between angiotensin-converting enzyme and angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase activation. Content: Activation of the renin-angiotensin system (angiotensin-converting enzyme [ACE]/angiotensin II [Ang II] and angiotensin-converting enzyme 2 [ACE2]/Ang-1-7) has been implicated in the pathophysiology of inflammatory response and acute lung injury (ALI). Previous studies have shown that the ACE inhibitor captopril (Cap) may be a potent therapeutic drug for ALI. However, the mechanisms of its protective effects on ALI are still largely unknown. In this study, we evaluated the effects of Cap on preventing lipopolysaccharide (LPS)-induced lung injury and further investigated the underlying mechanisms of these protective effects. Rats were intraperitoneally pretreated with Cap (50 mg/kg) 30 min prior to an intravenous administration of LPS (7.5 mg/kg). Furthermore, following a 30-min pretreatment with Cap (10 mol/mL) or combined with the ACE2 inhibitor MLN4760 (10 mol/mL), rat pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS (1 mg/mL). Captopril pretreatment significantly attenuated LPS-induced pathophysiological changes in the lung, inhibited secretion of tumor necrosis factor \u03b1 and interleukin 6, reduced the ratio of Ang II to Ang-1-7, and reversed the increased ratio of ACE to ACE2, which was remarkably decreased from 7.07 (LPS only) to 1.71 (LPS + Cap). The protective effects of Cap on ALI were also confirmed by in vitro studies, in which Cap suppressed LPS-induced secretion of proinflammatory cytokines and modulated the expression levels of ACE and ACE2. After Cap pretreatment, the ratio of ACE to ACE2 expression was remarkably decreased from 5.18 (LPS alone) to 1.52 (LPS + Cap). Furthermore, Cap given before LPS administration led to inhibition of p38 mitogen-activated protein kinase (MAPK), ERK (extracellular signal-regulated kinase) 1/2, and JNK (c-Jun N-terminal kinase) phosphorylation in PMVECs, whereas MLN4760 abolished the protective effects of Cap on LPS-induced secretion of proinflammatory cytokines and abolished Cap-induced blockade of p38MAPK, ERK1/2, and JNK phosphorylation. Our findings reveal that Cap exerts protective effects on LPS-induced lung injury and the cytotoxicity of PMVECs, and these effects may, at least in part, regulate the balance of ACE and ACE2 expression and inhibit the activation of MAPKs.", "qid": 20, "docid": "mfp453tb", "rank": 71, "score": 16.879499435424805}, {"content": "Title: Subchapter 29D Angiotensin Converting Enzymes Content: Abstract Angiotensin converting enzyme (ACE) is well known for its dual actions in converting inactive Ang I to active Ang II and degrade active bradykinin (BK), which play an important role in the control of blood pressure. Since the bottle neck step is the production of pressor Ang II, this was targeted pharmacologically in 1970s and successful ACE inhibitors such as captopril were produced to treat hypertension. Researches on domain specific ACE inhibitors are continuing to produce effective hypertension controlling drugs with fewer side effects. ACE2 was discovered in 2000; it converts Ang II into Ang(1\u20137), thereby reducing the concentration of Ang II as well as increasing that of Ang(1\u20137), an important enzyme for Ang(1\u20137)/Mas receptor signaling. ACE2 also acts as the receptor in the lung for the coronavirus causing the infamous severe acute respiratory syndrome (SARS) in 2003.", "qid": 20, "docid": "fexs1dm6", "rank": 72, "score": 16.869600296020508}, {"content": "Title: Residues affecting the chloride regulation and substrate selectivity of the angiotensin\u2010converting enzymes (ACE and ACE2) identified by site\u2010directed mutagenesis Content: Angiotensin\u2010converting enzyme (ACE) and its homologue angiotensin\u2010converting enzyme 2 (ACE2) are critical counter\u2010regulatory enzymes of the renin\u2013angiotensin system, and have been implicated in cardiac function, renal disease, diabetes, atherosclerosis and acute lung injury. Both ACE and ACE2 have catalytic activity that is chloride sensitive and is caused by the presence of the CL1 and CL2 chloride\u2010binding sites in ACE and the CL1 site in ACE2. The chloride regulation of activity is also substrate dependent. Site\u2010directed mutagenesis was employed to elucidate which of the CL1 and CL2 site residues are responsible for chloride sensitivity. The CL1 site residues Arg186, Trp279 and Arg489 of testicular ACE and the equivalent ACE2 residues Arg169, Trp271 and Lys481 were found to be critical to chloride sensitivity. Arg522 of testicular ACE was also confirmed to be vital to the chloride regulation mediated by the CL2 site. In addition, Arg514 of ACE2 was identified as a residue critical to substrate selectivity, with the R514Q mutant, relative to the wild\u2010type, possessing a fourfold greater selectivity for the formation of the vasodilator angiotensin\u2010(1\u20137) from the vasoconstrictor angiotensin II. The enhancement of angiotensin II cleavage by R514Q ACE2 was a result of a 2.5\u2010fold increase in V (max) compared with the wild\u2010type. Inhibition of ACE2 was also found to be chloride sensitive, as for testicular ACE, with residues Arg169 and Arg514 of ACE2 identified as influencing the potency of the ACE2\u2010specific inhibitor MLN\u20104760. Consequently, important insights into the chloride sensitivity, substrate selectivity and inhibition of testicular ACE and ACE2 were elucidated.", "qid": 20, "docid": "x21zlgyb", "rank": 73, "score": 16.843700408935547}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) \u2014a homologue of ACE\u2014to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 20, "docid": "1aal6njl", "rank": 74, "score": 16.824600219726562}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 20, "docid": "ubhntliy", "rank": 75, "score": 16.82459831237793}, {"content": "Title: Risks of ACE Inhibitor and ARB Usage in COVID\u201019: Evaluating the Evidence Content: Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID\u201019), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID\u201019. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "3ysa4twk", "rank": 76, "score": 16.82459831237793}, {"content": "Title: Risks of ACE Inhibitor and ARB Usage in COVID-19: Evaluating the Evidence Content: Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID-19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "xnu55d2t", "rank": 77, "score": 16.824596405029297}, {"content": "Title: ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS. Content: The intrapulmonary renin-angiotensin system via tissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients. In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls. Mortality was increased in the ACE DD genotype compared with the I allele, and the ACE I/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7-19.2) compared with the II genotype. In contrast, the AGT (-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome. In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.", "qid": 20, "docid": "uo1p1rim", "rank": 78, "score": 16.824399948120117}, {"content": "Title: Dangers of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence Content: Background: Concerns have been raised regarding the safety of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) in patients with COVID-19, based on the hypothesis that such medications may raise expression of ACE2, the receptor for SARS-CoV-2. Methods: We conducted a literature review of studies (n=12) in experimental animals and human subjects (n=11) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. Results: The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses than typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Conclusion: Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "mgp38mdz", "rank": 79, "score": 16.79050064086914}, {"content": "Title: Covid-19 and cardiovascular risk: Susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system. An evidence-based viewpoint Content: The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.", "qid": 20, "docid": "nfjkcmxu", "rank": 80, "score": 16.78260040283203}, {"content": "Title: Covid-19 and cardiovascular risk: susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system. An evidence-based viewpoint Content: Abstract The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.", "qid": 20, "docid": "ym8ue50x", "rank": 81, "score": 16.7825984954834}, {"content": "Title: ACE-inibitori, sartani e sindrome respiratoria acuta da coronavirus 2./ [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus] Content: Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.", "qid": 20, "docid": "mi0pmyo4", "rank": 82, "score": 16.760499954223633}, {"content": "Title: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 Content: RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.", "qid": 20, "docid": "h3xwg8uy", "rank": 83, "score": 16.744300842285156}, {"content": "Title: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 Content: RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55\u201368] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57\u201369]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19\u20130.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15\u20130.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12\u20130.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.", "qid": 20, "docid": "zmk8bbcd", "rank": 84, "score": 16.744298934936523}, {"content": "Title: Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts Content: BACKGROUND: Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas. METHODS: Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O(2)/5% CO(2)) or normoxic (21% O(2)/5% CO(2)) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein. RESULTS: Hyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-\u03b1\u2212converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05). CONCLUSION: These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2015.27) contains supplementary material, which is available to authorized users.", "qid": 20, "docid": "5n7hxhbg", "rank": 85, "score": 16.73259925842285}, {"content": "Title: Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis. Content: Earlier work from this laboratory showed that local generation of angiotensin (ANG) II is required for the pathogenesis of experimental pulmonary fibrosis and that ANG peptides are expressed robustly in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Angiotensin converting enzyme-2 (ACE-2) degrades the octapeptide ANG II to form the heptapeptide ANG1-7 and thereby limits ANG II accumulation. On this basis, we hypothesized that ACE-2 would be protective against experimental lung fibrogenesis and might be downregulated in human and experimental lung fibrosis. In lung biopsy specimens from patients with IPF, ACE-2 mRNA and enzyme activity were decreased by 92% (P<0.01) and 74% (P<0.05), respectively. ACE-2 mRNA and activity were also decreased similarly in the lungs of bleomycin-treated rats and C57-BL6 mice. In mice exposed to low doses of bleomycin, lung collagen accumulation was enhanced by intratracheal administration of either ACE-2-specific small interfering RNAs (siRNAs) or the peptide DX(600), a competitive inhibitor of ACE-2 (P<0.05). Administration of either ACE-2 siRNA or DX(600) significantly increased the ANG II content of mouse lung tissue above the level induced by bleomycin alone. Coadministration of the ANG II receptor antagonist saralasin blocked the DX(600)-induced increase in lung collagen. Moreover, purified recombinant human ACE-2, delivered to mice systemically by osmotic minipump, attenuated bleomycin-induced lung collagen accumulation. Together, these data show that ACE-2 mRNA and activity are severely downregulated in both human and experimental lung fibrosis and suggest that ACE-2 protects against lung fibrogenesis by limiting the local accumulation of the profibrotic peptide ANG II.", "qid": 20, "docid": "aiwuumcg", "rank": 86, "score": 16.71780014038086}, {"content": "Title: Local renin-angiotensin II systems, angiotensin-converting enzyme and its homologue ACE2: their potential role in the pathogenesis of chronic obstructive pulmonary diseases, pulmonary hypertension and acute respiratory distress syndrome. Content: Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, local renin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability to act as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. In the present paper, we review data from studies of the past decade that implicate AngII and functional polymorphisms of the ACE gene that increase ACE activity with increased susceptibility for asthma and chronic obstructive pulmonary disease (COPD) and for pulmonary hypertension. Moreover, drugs that inhibit the synthesis of AngII (ACE inhibitors) or that antagonize its actions on its receptors (Angiotensin II receptor blockers -ARBs) have been shown to provide beneficial effects. Another recent discovery reviewed is the presence of a homologue of ACE, ACE2, which cleaves a single amino acid from AngII and forms a heptapeptide with vasodilatory actions, Ang 1-7. The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE and ACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally, mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.", "qid": 20, "docid": "qjigokde", "rank": 87, "score": 16.706600189208984}, {"content": "Title: [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus]. Content: Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.", "qid": 20, "docid": "mclozg5p", "rank": 88, "score": 16.699800491333008}, {"content": "Title: Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes: systematic review and meta-analysis Content: Introduction: The effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies. This meta-analysis was undertaken to provide more conclusive evidence. Methods: A systematic search for published articles was performed in PubMed and EMBASE from January 5 2020 till May 5 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). Results: A total of 6,997 patients with COVID-19 were included, and all of them had hypertension. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). In addition, comparison of ACEIs to the rest of non-ACEI antihypertensives gave a consistently decreased risk of poor COVID-19 outcome (OR=0.77, 95% CI: [0.63-0.93]; P=0.002). However, ARBs did not decrease the risk of poor COVID-19 outcomes compared to all other non-ARB antihypertensives (OR=1.13, 95% CI: [0.95-1.35]). Conclusion: The risk of developing severe illness or death from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. ACEIs might be better in decreasing the severity and mortality of COVID-19 than ARBs.", "qid": 20, "docid": "ewf8wvge", "rank": 89, "score": 16.68950080871582}, {"content": "Title: Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial Content: Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN: BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.", "qid": 20, "docid": "7byl5jre", "rank": 90, "score": 16.689199447631836}, {"content": "Title: Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Content: BACKGROUND: Angiotensin-converting enzyme-2 (ACE2) may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 32 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from vascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, troponin, B-type natriuretic peptide, N-terminal-pro hormone and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.", "qid": 20, "docid": "ci0g1dno", "rank": 91, "score": 16.689197540283203}, {"content": "Title: Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China Content: Importance: Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective: To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants: Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures: COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results: Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance: This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "qid": 20, "docid": "m6pth0tu", "rank": 92, "score": 16.624300003051758}, {"content": "Title: Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. Content: Importance Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "qid": 20, "docid": "p10cya94", "rank": 93, "score": 16.624298095703125}, {"content": "Title: Activation of renin\u2013angiotensin\u2013aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats Content: OBJECTIVES: To explore the role of the renin\u2013angiotensin\u2013aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. METHODS: 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. RESULTS: After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (P<0.05), and ACE2 expression levels significantly increased. CONCLUSION: Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH.", "qid": 20, "docid": "ytzmvasb", "rank": 94, "score": 16.59830093383789}, {"content": "Title: COVID-19: Updated Data and its Relation to the Cardiovascular System. Content: In December 2019, a new human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) by the World Health Organization, emerged in the city of Wuhan, China. Spreading globally, it is now considered pandemic, with approximately 3 million cases worldwide at the end of April. Its symptoms include fever, cough, and headache, but the main one is shortness of breath. In turn, it is believed that there is a relationship between COVID-19 and damage to the heart muscle, and hypertensive and diabetic patients, for example, seem to have worse prognosis. Therefore, COVID-19 may worsen in individuals with underlying adverse conditions, and a not negligible number of patients hospitalized with this virus had cardiovascular or cerebrovascular diseases. Systemic inflammatory response and immune system disorders during disease progression may be behind this association. In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell. There is, however, no scientific evidence to support the interruption of these drugs. Since they are fundamental for certain chronic diseases, the risk and benefit of their withdrawal in this scenario should be carefully weighed. Finally, cardiologists and health professionals should be aware of the risks of infection and protect themselves as much as possible, sleeping properly and avoiding long working hours.", "qid": 20, "docid": "8hvv7gsm", "rank": 95, "score": 16.555299758911133}, {"content": "Title: Role of Drugs Affecting the Renin-Angiotensin-Aldosterone System on Susceptibility and Severity of COVID-19: A Large Case-Control Study from Zheijang Province, China. Content: Background. Medical editorials have suggested that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should not be given to people with arterial hypertension during the coronavirus disease 2019 (COVID-19) pandemic because of a potential increased risk of worse clinical outcomes and that calcium channel blockers (CCBs) should be used as an alternative. Methods Using a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China we have tested the role of usage of ACEIs, ARBs, CCBs and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Findings: Higher BMI, diabetes and cardio/ cerebrovascular disease as independent risk factors for the development of COVID-19. Individuals with hypertension taking CCBs had significantly increased risk [odds ratio (OR)= 1.67 (95% CI 1.2-2.9)) of manifesting symptoms of COVID-19 whereas those taking ARBs and diuretics had significantly lower disease risk (OR=0.24; 95%CI 0.17-0.34 and OR=0.32; 95%CI 0.19-0.57 respectively). Other antihypertensive drugs were not associated with increased risk of severe or critical form of the infection. Use of glucocorticoids was significantly associated with a severe/critical form of COVID-19 (OR= 7.56; 95%CI 1.17-48.93). Interpretation: we found no evidence to alter ARBs or ACEIs therapy in the context of the pandemic. Patients on corticosteroids with COVID-19 are at higher risk of developing a severe form of COVID-19and therefore should be monitored closely.", "qid": 20, "docid": "llzfc1r7", "rank": 96, "score": 16.52280044555664}, {"content": "Title: Role of Dipeptidyl Peptidase 4 Inhibitors in Diabetic Patients with Coronavirus-19 Infection. Content: The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It's reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin converting enzymes 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting with viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase 4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in diabetic patients. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.", "qid": 20, "docid": "dzvo9v01", "rank": 97, "score": 16.50659942626953}, {"content": "Title: Role of Dipeptidyl Peptidase 4 Inhibitors in Diabetic Patients with Coronavirus-19 Infection Content: The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It's reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin converting enzymes 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting with viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase 4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in diabetic patients. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.", "qid": 20, "docid": "wxhpo17g", "rank": 98, "score": 16.5065975189209}, {"content": "Title: [Drugs that aggravate the course of COVID-19 : really ?] Content: The safety of NSAIDs, corticosteroids and renin-angiotensin inhibitors in COVID-19 is challenged NSAIDs may interfere with the defense process against viral infection and are best avoided Systemic corticosteroids have not shown benefit in viral infection, including other coronavirus;thus they should be avoided, unless prescribed for another indication The benefit-risk ratio is however clearly in favor of continuing inhaled corticosteroids in patients with asthma or COPD ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2 Any possible clinical impact of these treatments on COVID-19 infection remains to be clarified;in the meantime, they should be continued", "qid": 20, "docid": "jxw6lr8d", "rank": 99, "score": 16.503999710083008}, {"content": "Title: [Drugs that aggravate the course of COVID-19 : really ?] Content: The safety of NSAIDs, corticosteroids and renin-angiotensin inhibitors in COVID-19 is challenged. NSAIDs may interfere with the defense process against viral infection and are best avoided. Systemic corticosteroids have not shown benefit in viral infection, including other coronavirus; thus they should be avoided, unless prescribed for another indication. The benefit-risk ratio is however clearly in favor of continuing inhaled corticosteroids in patients with asthma or COPD. ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2. Any possible clinical impact of these treatments on COVID-19 infection remains to be clarified; in the meantime, they should be continued.", "qid": 20, "docid": "xpfhf0gc", "rank": 100, "score": 16.503997802734375}]}
{"query": "what are the mortality rates overall and in specific populations", "hits": [{"content": "Title: Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns Content: For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.", "qid": 21, "docid": "0ie6tkgm", "rank": 1, "score": 8.981100082397461}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u20112 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 21, "docid": "e6k1bp9n", "rank": 2, "score": 8.719599723815918}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u00ad2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 21, "docid": "zt9mxom1", "rank": 3, "score": 8.719598770141602}, {"content": "Title: Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0\u00b75% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86\u00b79 years (95% UI 86\u00b77-87\u00b72), and for men in Singapore, at 81\u00b73 years (78\u00b78-83\u00b77) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. INTERPRETATION Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.", "qid": 21, "docid": "eet3v4cs", "rank": 4, "score": 8.656000137329102}, {"content": "Title: EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN. Content: Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.", "qid": 21, "docid": "0o3wjvpx", "rank": 5, "score": 8.522299766540527}, {"content": "Title: Global Mortality Impact of the 1957\u20131959 Influenza Pandemic Content: Background. Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. Methods. We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic. Results. The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2\u20132.6 cases/10 000 population) on average during 1957\u20131959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1\u20132 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%\u201377% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million\u20131.5 million excess deaths) globally to the 1957\u20131959 pandemic. Conclusions. The global mortality rate of the 1957\u20131959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.", "qid": 21, "docid": "ao5676lc", "rank": 6, "score": 8.508399963378906}, {"content": "Title: Mortality of Life\u2010Insured Swedish Cats during 1999\u20132006: Age, Breed, Sex, and Diagnosis Content: Background: A cat life insurance database can potentially be used to study feline mortality. Hypothesis: The aim was to describe patterns of mortality in life\u2010insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999\u20132006 were included. Methods: Age\u2010standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. Results: The total number of cats insured was 49,450 and the number of cat\u2010years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431\u2013493). Sex\u2010specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed\u2010specific (for most breeds) survival increased with time when analyzed by 2\u2010year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.", "qid": 21, "docid": "al3p52uj", "rank": 7, "score": 8.402999877929688}, {"content": "Title: Mortality among dentists in Taiwan, 1985\u20132009 Content: Background/Purpose Controversy exists in the literature regarding whether dentists with multiple occupational exposures suffer from premature mortality. A cohort mortality study was conducted to evaluate the survival outcome and determine if potential exposure to harmful agents leads to premature mortality among dentists. Methods Using the Life Table Analysis System, we calculated standardized mortality ratios (SMRs) for a cohort of 11,700 dentists affiliated with the Taiwan Dental Association. These dentists were followed from 1985\u20132009. Reference rates were derived from cause-, gender-, and age-specific mortality rates of the general population of Taiwan and 18,664 Taiwanese internists, who were considered to be more socioeconomically proximal to dentists. A Cox proportional hazard model was also constructed to determine multiple risk factors associated with mortality. Results Compared with the general population, dentists in Taiwan consistently demonstrated reduced from all-cause mortality. However, compared with internists, significant and excess mortality were observed in dentists for overall mortality (SMR=1.13; 95% confidence interval [CI]=1.00\u20131.26), drowning (SMR=6.62; 95% CI=2.15\u201315.45), and heart diseases (SMR=1.66; 95% CI=1.22\u20132.21). After adjusting for other risk factors, the Cox model showed an increased hazard ratio of 1.17 (95% CI=1.01\u20131.37) for dentists. Conclusion Taiwanese dentists demonstrated significant elevated SMRs for overall causes, drowning, and heart diseases. Careful precaution should be taken to reduce these trends. Future studies are also needed for in-depth exploration of the mechanisms regarding how professional stress and exposure contribute to the increased risk of mortality in Taiwanese dentists.", "qid": 21, "docid": "lr4l368z", "rank": 8, "score": 8.370200157165527}, {"content": "Title: Explaining the Neolithic Demographic Transition Content: Three main questions are raised in this chapter. 1. The part of the signal of the NDT which is demographically identifiable, based on the proportion of the immature skeletons in cemeteries, shows that a baby-boom occurred and, beyond that, with the onset of the change in the economic system, a fertility transition towards high values also occurred. What was the biodemographic cause of this fertility explosion, beyond the proxy variable represented by sedentarism? The cause is a major shift in the maternal energetics of farming communities relative to mobile foragers. In the energy balance there was (i) on the intake side, an underlying trend towards a reduction in low-calorie food from hunting and fishing, and a correlative increase in high-calorie food from agriculture, (ii) on the expenditure side, a reduction in the physical energy devoted to mobility and the maternal stress of child transportation. 2. The NDT is detectable from a signal representing a fertility transition, but the transition relating to mortality is missing and must be inferred. If, during the fertility transition, mortality had remained the same as in the preceding forager period, then the population would have grown infinitely. The assumption of unchanged mortality during the entire fertility transition is therefore not realistic. Mortality, in its turn, must have begun to rise well before the end of the fertility transition. But when? Why? One of the answers consists of a model where, except at the start of the process, birth and mortality rates rise more or less simultaneously, bringing about a typical rate of increase for pre-industrial populations of slightly above zero. 3. According to the level and speed of the population growth, what should we expect in terms of population structure? What are the expected effects of this growth, not only on the population in numbers but also on age distribution, the distribution and structure of families, the distribution of households and on family systems?", "qid": 21, "docid": "7655ggxz", "rank": 9, "score": 8.233099937438965}, {"content": "Title: Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020) Content: Objective. Scrutiny of COVID-19 mortality in Belgium over the period 8 March-9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates. Data. Publicly available COVID-19 mortality (2020); overall mortality (2009-2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020. Statistical methods. Reweighing, missing-data handling, rate estimation, visualization. Results. Belgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were similar in magnitude. Using various sero-prevalence estimates, infection fatality rates (IFRs; fraction of deaths among infected cases) are estimated at 0.38-0.73% for males and 0.20-0.39% for females in the non-nursing home population (non-NHP), and at 0.79-1.52% for males and 0.88-1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR and number of deaths per million is strongly influenced by extensive reporting and the fact that 66.0% of the deaths concerned NH residents. At 764 (our re-estimation of the figure 735, presented by \"Our World in Data\"), the number of COVID-19 deaths per million led the international ranking on May 9, 2020, but drops to 262 in the non-NHP. The NHP is very specific: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers and favor clustered outbreaks; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which is likely to contribute to this result.", "qid": 21, "docid": "qzb8a22l", "rank": 10, "score": 8.11460018157959}, {"content": "Title: The confounded crude case-fatality rates for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted rates between six countries Content: Background The reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude rates for comparisons are sometimes overlooked. In this paper we examined to what extent the age distribution of the cases is responsible for the differences in CFRs between countries. Methods Data on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population. Findings The age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest to that with the lowest, was reduced substantially from 7.4 to 2.3 for the age-adjusted rates. Conclusions The age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. Comparisons should be based on age-specific and age-adjusted rates. Key words: COVID-19, case-fatality rates, age-specific rates, age-adjusted rates, confounding", "qid": 21, "docid": "2apo9imk", "rank": 11, "score": 8.08430004119873}, {"content": "Title: The COVID-19 mortality effects of underlying health conditions in India: a modelling study Content: Objective: To model how known COVID-19 comorbidities will affect mortality rates and the age distribution of mortality in a large lower middle income country (India), as compared with a high income country (England), and to identify which health conditions drive any differences. Design: Modelling study. Setting: England and India. Participants: 1,375,548 respondents aged 18 to 99 to the District Level Household Survey-4 and Annual Health Survey in India. Additional information on health condition prevalence on individuals aged 18 to 99 was obtained from the Health Survey for England and the Global Burden of Diseases, Risk Factors, and Injuries Studies (GBD). Main outcome measures: The primary outcome was the proportional increase in age-specific mortality in each country due to the prevalence of each COVID-19 mortality risk factor (diabetes, hypertension, obesity, chronic heart disease, respiratory illness, kidney disease, liver disease, and cancer, among others). The combined change in overall mortality and the share of deaths under 60 from the combination of risk factors was estimated in each country. Results: Relative to England, Indians have higher rates of diabetes (10.6% vs. 8.5%), chronic respiratory disease (4.8% vs. 2.5%), and kidney disease (9.7% vs. 5.6%), and lower rates of obesity (4.4% vs. 27.9%), chronic heart disease (4.4% vs. 5.9%), and cancer (0.3% vs. 2.8%). Population COVID-19 mortality in India relative to England is most increased by diabetes (+5.4%) and chronic respiratory disease (+2.3%), and most reduced by obesity (-9.7%), cancer (-3.2%), and chronic heart disease (-1.9%). Overall, comorbidities lower mortality in India relative to England by 9.7%. Accounting for demographics and population health explains a third of the difference in share of deaths under age 60 between the two countries. Conclusions: Known COVID-19 health risk factors are not expected to have a large effect on aggregate mortality or its age distribution in India relative to England. The high share of COVID-19 deaths from people under 60 in low- and middle-income countries (LMICs) remains unexplained. Understanding mortality risk associated with health conditions prevalent in LMICs, such as malnutrition and HIV/AIDS, is essential for understanding differential mortality. Keywords: COVID-19, India, low- and middle-income countries, comorbidity", "qid": 21, "docid": "ekaqbruo", "rank": 12, "score": 8.067000389099121}, {"content": "Title: Human agency and infection rates: implications for social distancing during epidemics Content: Social distancing is an important measure in controlling epidemics. This paper presents a simple theoretical model focussed on the implications of the wide range in interaction rates between individuals, both within the workplace and in the social setting. The model is based on well-mixed populations and so is not intended for studying geographic spread. The model shows that epidemic growth rate is largely determined by the upper interactivity quantiles of society, implying that the most efficient methods of epidemic control are interaction capping approaches rather than overall reductions in interaction. The theoretical model can also be applied to look at the dynamics of epidemic progression under various scenarios. The theoretical model suggests that with no intervention herd immunity would be achieved with a lower overall infection rate than if variation in interaction rate is ignored, because by this stage almost all the most interactive members of society would have had the infection; however the overall mortality with such an approach is very high. Scenarios for mitigation and suppression suggest that, by using interactivity capping, it should be possible to control an epidemic without extreme sanctions on the majority of the population if R0 of the uncontrolled infection is 2.4. However to control the infection rate to a specific level will always require the switching on and off of measures and for this reason eradication is likely to be a less costly policy in the long run. While social distancing alone can be used for eradication it is not be a good mechanism on its own to prevent reinfection. The use of robust testing, quarantining, and contact tracing would strengthen any social distancing measures, speed up eradication, and be a better tool for prevention of infection or reinfection.", "qid": 21, "docid": "dcmcog6l", "rank": 13, "score": 7.922100067138672}, {"content": "Title: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units Content: This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.", "qid": 21, "docid": "vpakh3jk", "rank": 14, "score": 7.895699977874756}, {"content": "Title: Behavioural responses to influenza pandemics: what do we know? Content: The emergence of the novel A/H1N1 virus has made pandemic preparedness a crucial issue for public health worldwide. Although the epidemiological aspects of the three 20th century influenza pandemics have been widely investigated, little is known about population behaviour in a pandemic situation. Such knowledge is however critical, notably for predicting population compliance with non pharmaceutical interventions. This paper reviews the relevant scientific literature for the 1918-1920, 1957-1958, 1969-1969 influenza epidemics and the 2003 SARS outbreak. Although the evidence base of most non pharmaceutical interventions (NPIs) and personal protection measures is debated, it appears on the basis of past experience that NPIs implemented the most systematically, the earliest, and for the longest time could reduce overall mortality rates and spread out epidemic peaks. Adequate, transparent, and targeted communication on the part of public health authorities would be also of crucial importance in the event of a serious influenza pandemic.", "qid": 21, "docid": "92o213bg", "rank": 15, "score": 7.8379998207092285}, {"content": "Title: Viet Nam. Content: Attention in this discussion of Viet Nam focuses on the following: history of the demographic situation; the government's overall approach to population problems; population data systems and development planning; institutional arangements for the integration of population within development planning; the government's view of the importance of population policy in achieving development objectives; population size, growth, and natural increase; morbidity and mortality; fertility; international migration; and spatial distribution. Relatively little information has been available on demographic trends in Viet Nam due to the absence of any major survey or census until the last few decades. The government increasingly has been concerned about the high rate of population growth and is working to change the situation through programs directed at fertility reduction. As part of its program for overall social and economic restructuring, the government seeks to give special attention to health problems, particularly those relating to maternal and child health and environmental sanitation. Population censuses in Viet Nam have been undertaken only in the last 2 decades, with censuses conducted in the North in 1960 and 1974. No population census was undertaken in the South, and any population information available was based upon the periodic population and household surveys conducted alternately in different provinces, cities, and rural areas during 1962, 1967, 1971, and 1974. The government considers the formulation and implementation of population policy to be a critical variable for realizing national development objectives. The population of Viet Nam has grown considerably since the 1950s, increasing from over 30 million in 1950 to 35.4 million in 1960 and reaching 43.1 million by 1970, according to UN estimates. 1979 census results indicate that the population of Viet Nam had reached 52.7 million. The current rate of growth is estimated at 2.2%. The government perceives the current rate of population growth as unsatisfactory because it is too high. The official government policy is to take steps to reduce the rate of population growth as rapidly as possible. All 3 demographic factors--mortality, fertility, and spatial distribution--are viewed as subject to direct policy intervention to achieve this goal. Rates of morbidity and mortality have declined considerably in the past few decades. The government reports a decline in the crude death rate from 12.2 in 1957 to 7.0 in 1980 and an increase in the life expectancy at birth from 34 years in 1936 to 60 in 1978. UN estimates are considerably higher. According to UN estimates, the infant mortality rate was 90.3/1000 live births during 1975-80 for Viet Nam as a whole. The current mortality and morbidity situation is considered to be unacceptable. The government estimates the crude birthrate as 29.3/1000 in 1980, an unsatisfactory level. The government perceives the present levels and trends of immigration as not significant and satisfactory and the spatial distribution as inappropriate.", "qid": 21, "docid": "ir77zvrr", "rank": 16, "score": 7.828000068664551}, {"content": "Title: Is investing in religious institutions a viable pathway to reduce mortality in the population? Content: There is established and consistent findings from epidemiologic studies, among individuals, that religion\u2014 broadly assessed through frequency of attending worship services\u2014is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.", "qid": 21, "docid": "l42w2jyk", "rank": 17, "score": 7.818399906158447}, {"content": "Title: Male mortality and the German response: lessons from COVID\u201019 Content: The current COVID\u201019 outbreak has raised many questions, amongst them the higher mortality rates in men and the low overall mortality rates in Germany compared to other European countries. Here the authors explore some of the reasons behind both these phenomena and outline what we can learn from them for the future.", "qid": 21, "docid": "2vxnmiyj", "rank": 18, "score": 7.761899948120117}, {"content": "Title: Determinants of COVID-19 incidence and mortality: A cross-country analysis Content: Objective: We undertook this study to explore the role of important determinants affecting global COVID-19 incidence and mortality taking multifactorial disease dynamics into consideration. Design: Secondary data as on March 28, 2020 were obtained for 97 countries. Association of COVID-19 cumulative incidence and mortality measures were assessed with ten indictors representing health system characteristics, climate, demography, promptness of international travel restriction and population movement using Generalized Linear Modelling. Main outcome measures: Country-specific COVID-19 cumulative incidence, cumulative cause-specific mortality and case fatality rate. Results: Significant inter-country variation in incidence and mortality rates were observed. Five variables were found to be associated with cumulative incidence: testing rate per 1000 population ({beta} = 0.119, p < 0.01), UHC index ({beta} = 0.043, p = 0.04), percentage elderly population ({beta} = 0.122, p < 0.01), percentage below-poverty line population ({beta} = -0.048, p < 0.01) and disability adjusted life years due to NCDs ({beta} = -0.013, p < 0.01). Case fatality rate was observed to be associated with testing rate per 1000 population ({beta} = -0.058, p = 0.03) and population density ({beta} = 0.002, p = 0.02), while the cumulative cause-specific mortality was associated with only percentage elderly population ({beta} = 0.096, p = 0.04) in the country. Conclusions: Health system response, population susceptibility and demography were the most important factors determining the progression. Policy response should focus towards increasing testing, primarily targeting high population density areas. Health system strengthening and reduction in population risk factors should be long term goals for a better response to such epidemics.", "qid": 21, "docid": "u72yj5kx", "rank": 19, "score": 7.673699855804443}, {"content": "Title: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters Content: OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus \u226565 years old; absolute risk of COVID-19 death in people <65 and in those \u226580 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5\u201311.2% of all COVID-19 deaths in European countries and Canada, 8.3\u201322.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those \u226565 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people \u226580 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106\u2013483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7\u20133.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.", "qid": 21, "docid": "f3eogz0n", "rank": 20, "score": 7.546800136566162}, {"content": "Title: Pediatrician, watch out for corona-phobia Content: The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians\u2019 everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call \u201cCorona-phobia\u201d. These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon. In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration.", "qid": 21, "docid": "gi4t0dpt", "rank": 21, "score": 7.537899971008301}, {"content": "Title: When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico Content: During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60\u201370% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.", "qid": 21, "docid": "vokdqskd", "rank": 22, "score": 7.445499897003174}, {"content": "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain Content: Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic. We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates. Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty. Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups. The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk. Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919. Little evidence was found to support a \u201cW\u201d-shaped, age-specific excess mortality curve. Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.", "qid": 21, "docid": "36fljyl2", "rank": 23, "score": 7.440400123596191}, {"content": "Title: Impact of Political Economy on Population Health: A Systematic Review of Reviews. Content: Background. Although there is a large literature examining the relationship between a wide range of political economy exposures and health outcomes, the extent to which the different aspects of political economy influence health, and through which mechanisms and in what contexts, is only partially understood. The areas in which there are few high-quality studies are also unclear. Objectives. To systematically review the literature describing the impact of political economy on population health. Search Methods. We undertook a systematic review of reviews, searching MEDLINE, Embase, International Bibliography of the Social Sciences, ProQuest Public Health, Sociological Abstracts, Applied Social Sciences Index and Abstracts, EconLit, SocINDEX, Web of Science, and the gray literature via Google Scholar. Selection Criteria. We included studies that were a review of the literature. Relevant exposures were differences or changes in policy, law, or rules; economic conditions; institutions or social structures; or politics, power, or conflict. Relevant outcomes were any overall measure of population health such as self-assessed health, mortality, life expectancy, survival, morbidity, well-being, illness, ill health, and life span. Two authors independently reviewed all citations for relevance. Data Collection and Analysis. We undertook critical appraisal of all included reviews by using modified Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria and then synthesized narratively giving greater weight to the higher-quality reviews. Main Results. From 4912 citations, we included 58 reviews. Both the quality of the reviews and the underlying studies within the reviews were variable. Social democratic welfare states, higher public spending, fair trade policies, extensions to compulsory education provision, microfinance initiatives in low-income countries, health and safety policy, improved access to health care, and high-quality affordable housing have positive impacts on population health. Neoliberal restructuring seems to be associated with increased health inequalities and higher income inequality with lower self-rated health and higher mortality. Authors' Conclusions. Politics, economics, and public policy are important determinants of population health. Countries with social democratic regimes, higher public spending, and lower income inequalities have populations with better health. There are substantial gaps in the synthesized evidence on the relationship between political economy and health, and there is a need for higher-quality reviews and empirical studies in this area. However, there is sufficient evidence in this review, if applied through policy and practice, to have marked beneficial health impacts. Public Health Implications. Policymakers should be aware that social democratic welfare state types, countries that spend more on public services, and countries with lower income inequalities have better self-rated health and lower mortality. Research funders and researchers should be aware that there remain substantial gaps in the available evidence base. One such area concerns the interrelationship between governance, polities, power, macroeconomic policy, public policy, and population health, including how these aspects of political economy generate social class processes and forms of discrimination that have a differential impact across social groups. This includes the influence of patterns of ownership (of land and capital) and tax policies. For some areas, there are many lower-quality reviews, which leave uncertainties in the relationship between political economy and population health, and a high-quality review is needed. There are also areas in which the available reviews have identified primary research gaps such as the impact of changes to housing policy, availability, and tenure.", "qid": 21, "docid": "nn3q1hw5", "rank": 24, "score": 7.428699970245361}, {"content": "Title: Influenza and the challenge for immunology. Content: The continued westward dissemination of H5N1 influenza A viruses in avian populations and the nearly 50% mortality rate of humans infected with H5N1 are a source of great international concern. A mutant H5N1 virus with the capability to spread rapidly between humans could cause a global catastrophe. Governments have reacted by developing national response plans, stockpiling antiviral drugs and speeding up the development and approval of vaccines. Here we summarize what is known about the interaction between influenza A viruses and the mammalian host response, specifically emphasizing issues that might be of interest to the broader immunology community.", "qid": 21, "docid": "53bw4z9u", "rank": 25, "score": 7.418900012969971}, {"content": "Title: High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety. Content: OBJECTIVE To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.", "qid": 21, "docid": "z957wfop", "rank": 26, "score": 7.417200088500977}, {"content": "Title: The epidemiology of invasive meningococcal disease and the utility of vaccination in Malta Content: Invasive meningococcal disease (IMD) is a vaccine-preventable devastating infection that mainly affects infants, children and adolescents. We describe the population epidemiology of IMD in Malta in order to assess the potential utility of a meningococcal vaccination programme. All cases of microbiologically confirmed IMD in the Maltese population from 2000 to 2017 were analysed to quantify the overall and capsular-specific disease burden. Mean overall crude and age-specific meningococcal incidence rates were calculated to identify the target age groups that would benefit from vaccination. Over the 18-year study period, 111 out of the 245 eligible notified cases were confirmed microbiologically of which 70.3% had septicaemia, 21.6% had meningitis, and 6.3% had both. The mean overall crude incidence rate was 1.49/100,000 population with an overall case fatality rate of 12.6%. Meningococcal capsular groups (Men) B followed by C were the most prevalent with W and Y appearing over the last 6 years. Infants had the highest meningococcal incidence rate of 18.9/100,000 followed by 6.1/100,000 in 1\u20135 year olds and 3.6/100,000 in 11\u201315 year old adolescents. The introduction of MenACWY and MenB vaccines on the national immunization schedule in Malta would be expected to reduce the disease burden of meningococcal disease in children and adolescents in Malta.", "qid": 21, "docid": "a5q15dq1", "rank": 27, "score": 7.402699947357178}, {"content": "Title: Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan Content: Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.", "qid": 21, "docid": "3jmxamtj", "rank": 28, "score": 7.384500026702881}, {"content": "Title: Epidemiology of Human and Animal Viral Diseases Content: Viral disease epidemiology is the study of the determinants, dynamics, and distribution of viral diseases in populations. The risk of infection or disease in a population is determined by characteristics of the virus, the host, and the host population, as well as behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Information on incidence, prevalence, and morbidity and mortality rates contributes directly to the establishment of priorities for prevention and control programs, whether this involves vaccine or drug development and delivery, environmental and hygienic improvements, enhancement of nutritional status, personal or community behavior, agricultural and food processing enhancements, reservoir host and vector control, and international cooperation and communication.", "qid": 21, "docid": "nquov2i0", "rank": 29, "score": 7.383399963378906}, {"content": "Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK\u2013CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1\u00b75, 2\u00b70, and 3\u00b70 at differing infection rate scenarios, including full suppression (0\u00b7001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50\u00b77%] women and 1 904 077 [49\u00b73%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13\u00b77% were older than 70 years and 6\u00b73% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4\u00b746% (95% CI 4\u00b741\u20134\u00b751). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1\u00b75, four with an RR of 2\u00b70, and seven with an RR of 3\u00b70. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1\u00b75, 36 749 with an RR of 2\u00b70, and 73 498 with an RR of 3\u00b70. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1\u00b75, 293 991 with an RR of 2\u00b70, and 587 982 with an RR of 3\u00b70. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.", "qid": 21, "docid": "ml4fpf2o", "rank": 30, "score": 7.379700183868408}, {"content": "Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1\u00b75, 2\u00b70, and 3\u00b70 at differing infection rate scenarios, including full suppression (0\u00b7001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3\u00e2\u0080\u0088862\u00e2\u0080\u0088012 individuals (1\u00e2\u0080\u0088957\u00e2\u0080\u0088935 [50\u00b77%] women and 1\u00e2\u0080\u0088904\u00e2\u0080\u0088077 [49\u00b73%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13\u00b77% were older than 70 years and 6\u00b73% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4\u00b746% (95% CI 4\u00b741-4\u00b751). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1\u00b75, four with an RR of 2\u00b70, and seven with an RR of 3\u00b70. In a mitigation scenario, we estimated 18\u00e2\u0080\u0088374 excess deaths with an RR of 1\u00b75, 36\u00e2\u0080\u0088749 with an RR of 2\u00b70, and 73\u00e2\u0080\u0088498 with an RR of 3\u00b70. In a do nothing scenario, we estimated 146\u00e2\u0080\u0088996 excess deaths with an RR of 1\u00b75, 293\u00e2\u0080\u0088991 with an RR of 2\u00b70, and 587\u00e2\u0080\u0088982 with an RR of 3\u00b70. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.", "qid": 21, "docid": "qsk9lmsc", "rank": 31, "score": 7.379699230194092}, {"content": "Title: Injecting epidemiology into population viability analysis: avian cholera transmission dynamics at an arctic seabird colony. Content: Infectious diseases have the potential to spread rapidly and cause high mortality within populations of immunologically na\u00efve hosts. The recent appearance of avian cholera, a highly virulent disease of birds caused by the bacterium Pasteurella multocida, at remote Arctic seabird colonies is an emerging conservation concern. Determining disease risk to population viability requires a quantitative understanding of transmission potential and the factors that regulate epidemic persistence. Estimates of the basic (R0 ) and real-time (Rt ) reproductive number are critical in this regard - enumerating the number of secondary infections caused by each primary infection in a newly invaded host population and the decline in transmission rate as susceptible individuals are removed via mortality or immunized recovery. Here, we use data collected at a closely monitored common eider (Somateria mollissima) breeding colony located in the Canadian Arctic to examine transmission and host population dynamics. Specifically, we infer epidemic curves from daily mortality observations and use a likelihood-based procedure to estimate changes in the reproductive number over a series of annual outbreaks. These data are interpreted in relation to concurrent changes in host numbers to assess local extinction risk. Consistent with expectations for a novel pathogen invasion, case incidence increased exponentially during the initial wave of exposure (R0 = 2\u00b75; generation time = 6\u00b75 days \u00b1 1\u00b71 SD). Disease conditions gradually abated, but only after several years of smouldering infection (Rt \u2248 1). In total, 6194 eider deaths were recorded during outbreaks spanning eight consecutive breeding seasons. Breeding pair abundance declined by 56% from the pre-outbreak peak; however, a robust population of >4000 pairs remained intact upon epidemic fade-out. Overall, outbreak patterns were consistent with herd immunity acting as a mitigating factor governing in the extent and duration of mortality. Disease mortality is frequently modelled as a form of stochastic catastrophe in wildlife population assessments, whereas our approach gives shape to the functional response between transmission and host population dynamics. We conclude that increased emphasis on integrating epidemiological and population processes is essential to predicting the conservation impact of emerging infectious diseases in wildlife.", "qid": 21, "docid": "wc3gas1k", "rank": 32, "score": 7.360899925231934}, {"content": "Title: Impacts of Early Interventions on the Age-Specific Incidence of COVID-19 in New York, Los Angeles, Daegu and Nairobi Content: Background COVID-19 has caused an unprecedented public health crisis and economic shock to the global economy. While many countries were affected, regions with an older population and weaker public health interventions tended to suffer more morbidity and mortality. Here we model and quantify the age-specific incidence of COVID-19 in four pandemic cities under different interventions. Methods We developed an age-specific and multiple-stage susceptible-exposed-infected-recovered-hospitalized-quarantined-dead (SEIR-HQD) dynamical systems model expanded from the more basic SEIR model by incorporating location- and age-specific contact matrices to estimate the outcomes of COVID-19. Utilizing latest estimates of epidemiological parameters and demographic data, we model the potential effects of various interventions in four representative cities with different population structures - New York, Los Angeles, Daegu and Nairobi. We compared the effects of different interventions in the age-structure populations specific to each city. These policy options are then applied to determine the potential for effective containment. We model these dynamic policy scenarios to assess the risks of less-stringent social distancing, as has been proposed by those arguing to enhance economic activity over public health and safety. Finally, we explored the health impacts of different policy action timelines to understand the benefits of early interventions. Findings We find the spread of COVID-19 to be dramatically different in the regions modeled, with the primary drivers the variation of population age structures, and the dynamics of interactions of the younger demographics, whose higher interaction rates can lead to increasing transmission rates across these communities. A city with younger citizens may also have fewer hospitalized cases and deaths. Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities. The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections. Interpretation Moderate social distancing together with high quarantine rates was effective in each of the four cities. COVID-19 caused more deaths and hospitalization in cities with an ageing population than those with a younger population. However, in the cities with a younger population, there is a clear need to implement a social distancing strategy that is even more strict due to the higher transmission rates among younger people. Cities with more older people should prepare more hospital beds and healthcare facilities to save people who are in critical conditions. Cities with ageing population should take targeted action for the elderly to avoid the severe impacts on the vulnerable populations. Increasing quarantine rate is an effective strategy to avoid the substantial infection while also does not influence the economy fiercely. We recommend countries or regions experiencing, or likely to experience the rapid spread of COVID-19, to implement combination of multiple strategies in the early stage of the breakout which can avoid over 90% of infected cases.", "qid": 21, "docid": "5zg3xr69", "rank": 33, "score": 7.344799995422363}, {"content": "Title: Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto Content: BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93\u20131.06] compared to 2002 and 0.96 [95% CI 0.90\u20131.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.", "qid": 21, "docid": "ou3wj4rz", "rank": 34, "score": 7.308199882507324}, {"content": "Title: Effects of latency and age structure on the dynamics and containment of COVID-19 Content: In this paper we develop an SEIR-type model of COVID-19, with account for two particular aspects: non-exponential distribution of incubation and recovery periods, as well as age structure of the population. For the mean-field model, which does not distinguish between different age groups, we demonstrate that including a more realistic Gamma distribution of incubation and recovery periods may not have an effect on the total number of deaths and the overall size of an epidemic, but it has a major effect in terms of increasing the peak numbers of infected and critical care cases, as well as on changing the timescales of an epidemic, both in terms of time to reach the peak, and the overall duration of an outbreak. In order to obtain more accurate estimates of disease progression and investigate different strategies for introducing and lifting the lockdown, we have also considered an age-structured version of the model, which has allowed us to include more accurate data on age-specific rates of hospitalisation and COVID-19 related mortality. Applying this model to three comparable neighbouring regions in the UK has delivered some fascinating insights regarding the effect of quarantine in regions with different population structure. We have discovered that for a fixed quarantine duration, the timing of its start is very important in the sense that the second epidemic wave after lifting the quarantine can be significantly smaller or larger depending on the specific population structure. Also, the later the fixed-duration quarantine is introduced, the smaller is the resulting final number of deaths at the end of the outbreak. When the quarantine is introduced simultaneously for all regions, increasing quarantine duration postpones and slightly reduces the epidemic peak, though without noticeable differences in peak magnitude between different quarantine durations.", "qid": 21, "docid": "rv06wb3x", "rank": 35, "score": 7.301199913024902}, {"content": "Title: Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome Content: PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients. METHODS: We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling. RESULTS: Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51\u20134.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86\u20132.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58\u20131.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6\u201341) by day 30 (risk difference 4.4, 95 % CI 1.1\u20137.9). CONCLUSION: CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-4071-z) contains supplementary material, which is available to authorized users.", "qid": 21, "docid": "n2d5fw2f", "rank": 36, "score": 7.287099838256836}, {"content": "Title: Association of Bacille Calmette-Guerin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries Content: Introduction Non-specific effects of vaccines have gained increasing interest during the Covid-19 pandemic. In particular, population use of BCG vaccine has been associated with improved outcomes. This study sought to determine the association of population use of BCG, adult pneumococcal and adult seasonal influenza vaccination with Covid-19 mortality when adjusted for a number of confounding variables. Methods: Using publicly available data, mortality adjusted for the timeframe of crisis, population size and population characteristics was calculated. The primary analysis was the relationship between each of the day 15 and day 30 standardised mortality rates and BCG, adult pneumococcal and influenza vaccination scores using unadjusted measures and with adjustment for population structure and case fatality rates. Secondary analyses were measures of case increases and mortality increases from day 15 to day 30 for each of the relative vaccination scores. Finally, we also analysed the peak Z score reflecting increases in total mortality from historical averages reported by EuroMOMO (Euromomo.eu), Results: Following adjustment for the effects of population size, median age, population density, the proportion of population living in an urban setting, life-expectancy, the elderly dependency ratio (or proportion over 65 years), net migration, days from day 1 to lockdown and case-fatality rate, only BCG vaccination score remained significantly associated with Covid-19 mortality at day 30. In the best fit model, BCG vaccination score was associated with a 64% reduction in log(10) mortality per 10 million population (OR 0.362 reduction [95% CI 0.188 to 0.698]), following adjustment for population size, median age, density, urbanization, elderly dependency ratio, days to lockdown, yearly migration and case fatality rate. Conclusion BCG vaccine was associated with reduced mortality rates in level 4 countries while adult pneumococcal and adult seasonal influenza vaccines were not when adjusted for a number of confounding variables. A number of trials are ongoing to determine if BCG is protective against severe Covid-19 infection.", "qid": 21, "docid": "leu2hygk", "rank": 37, "score": 7.168300151824951}, {"content": "Title: The potential effect of the African population age structure on COVID-19 mortality Content: Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.", "qid": 21, "docid": "vzmn6zep", "rank": 38, "score": 7.142399787902832}, {"content": "Title: Addressing inequities in COVID-19 morbidity and mortality: research and policy recommendations Content: The COVID-19 pandemic is the greatest global public health crisis since the 1918 influenza outbreak. As of early June, the novel coronavirus has infected more than 6.3 million people worldwide and more than 1.9 million in the United States (US). The total number of recorded deaths due to COVID-19 are growing at an alarming rate globally (\u00b3383,000) and nationally (\u00b3109,000) Evidence is mounting regarding the heavier burden of COVID-19 infection, morbidity, and mortality on the underserved populations in the US. This commentary focuses on this global health pandemic and how mitigation of the virus relies heavily on health behavior change to slow its spread, highlighting how the pandemic specifically affects the most socially and economically disadvantaged populations in the US. The commentary also offers short, intermediate and long-term research and policy focused recommendations. Both the research and policy recommendations included in this commentary emphasize equity-driven: (1) research practices, including applying a social determinants and health equity lens on monitoring, evaluation, and clinical trials activities on COVID-19; and (2) policy actions, such as dedicating resources to prioritize high-risk communities for testing, treatment, and prevention approaches and implementing organizational, institutional, and legislative policies that address the social and economic barriers to overall well-being that these populations face during a pandemic. It is our hope that these recommendations will generate momentum in delivering timely, effective, and lifesaving changes.", "qid": 21, "docid": "n5b1kzlw", "rank": 39, "score": 7.133600234985352}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 21, "docid": "ekxz577j", "rank": 40, "score": 7.114699840545654}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015\u20132019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID\u201319 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 21, "docid": "t9qdiz7n", "rank": 41, "score": 7.114698886871338}, {"content": "Title: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons Content: CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1\u2014the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (\u2212.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also \u2212.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.", "qid": 21, "docid": "peg0m87x", "rank": 42, "score": 7.097499847412109}, {"content": "Title: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach Content: Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.", "qid": 21, "docid": "8hvve871", "rank": 43, "score": 7.089099884033203}, {"content": "Title: Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population Content: COVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.", "qid": 21, "docid": "afbvbgq5", "rank": 44, "score": 7.065899848937988}, {"content": "Title: Burden of serious fungal infections in the Netherlands Content: BACKGROUND: Fungal diseases have an ever\u2010increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. OBJECTIVES: Here, we report the current annual burden of life\u2010threatening and debilitating fungal diseases in the Netherlands. METHODS: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. RESULTS: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo\u2010vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. CONCLUSION: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality.", "qid": 21, "docid": "qabil0vc", "rank": 45, "score": 7.034900188446045}, {"content": "Title: Confinement strategies in a simple SIR model Content: We propose a simple SIR model in order to investigate the impact of various confinement strategies on a most virulent epidemic. Our approach is motivated by the current COVID-19 pandemic. The main hypothesis is the existence of two populations of susceptible persons, one which obeys confinement and for which the infection rate does not exceed 1, and a population which, being non confined for various imperatives, can be substantially more infective. The model, initially formulated as a differential system, is discretised following a specific procedure, the discrete system serving as an integrator for the differential one. Our model is calibrated so as to correspond to what is observed in the COVID-19 epidemic. Several conclusions can be reached, despite the very simple structure of our model. First, it is not possible to pinpoint the genesis of the epidemic by just analysing data from when the epidemic is in full swing. It may well turn out that the epidemic has reached a sizeable part of the world months before it became noticeable. Concerning the confinement scenarios, a universal feature of all our simulations is that relaxing the lockdown constraints leads to a rekindling of the epidemic. Thus we sought the conditions for the second epidemic peak to be lower than the first one. This is possible in all the scenarios considered (abrupt, progressive or stepwise exit) but typically a progressive exit can start earlier than an abrupt one. However, by the time the progressive exit is complete, the overall confinement times are not too different. From our results, the most promising strategy is that of a stepwise exit. And in fact its implementation could be quite feasible, with the major part of the population (minus the fragile groups) exiting simultaneously but obeying rigorous distancing constraints.", "qid": 21, "docid": "zy1608lw", "rank": 46, "score": 7.020400047302246}, {"content": "Title: Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador Content: Abstract Background: The SARS-CoV-2 virus has spread all over the world infecting more than 3,585,936 people from over 210 countries and caused more than 245,803 deaths worldwide. We report the first epidemiological, socio-demographic, and clinical findings for the first 9,468 confirmed COVID-19 cases in Ecuador. Methods: We conducted a descriptive cross-sectional analysis of 9,468 COVID-19 confirmed cases in Ecuador from 27 February to 18 April 2020. The overall incidence, mortality, and case fatality rate was computed according to the entire population at risk living in a canton or a province. Disability adjusted life years, attack and crude mortality rates as well as relative risk and odds ratios were computed as an outcome. Results: Since the first case reported in Ecuador on 27 Feb 2020, at least 9,468 positive COVID-19 cases of which 474 deaths were officially registered over a 54-day period. Men accounted for 55.40% (n = 5, 247) of the overall cases with an incidence rate of 60.5 per 100,000 while women accounted for 44.60 % (n = 4, 221) representing 47.2 per 100,000. The mortality rate per canton showed that cantons with a lower attack rate had higher mortality rates. Coastal cantons have a lower attack rate than the highlands and living above >2,500 m seems to be linked with a lower risk of dying (RR: 0.63 [CI 95% 0.50 - 0.79]). Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: This study is the first of its kind in Ecuador. The results of this analysis show that men are at higher risk of dying from COVID-19 than women, which increases as with age and the presence of comorbidities. Areas with better testing capabilities reported lower CFR% and mortality, additionally cantons located above 2,500 m have lower attack and mortality rates although the risk of dying is greater among highlanders. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America", "qid": 21, "docid": "rrohv3to", "rank": 47, "score": 6.9934000968933105}, {"content": "Title: Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome Content: Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in \u201cat risk\u201d populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.", "qid": 21, "docid": "o7qfugjw", "rank": 48, "score": 6.990799903869629}, {"content": "Title: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Content: We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.", "qid": 21, "docid": "xr4flvzx", "rank": 49, "score": 6.955999851226807}, {"content": "Title: An empirical estimate of the infection fatality rate of COVID-19 from the first Italian outbreak Content: Background: The coronavirus 2019 (COVID-19) pandemic has been spread-ing globally for months, yet the infection fatality ratio of the disease is still uncertain. This is partly because of inconsistencies in testing and death reporting standards across countries. Our purpose is to provide accurate estimates which do not rely on testing and death count data directly but only use population level statistics. Methods: We collected demographic and death records data from the Italian Institute of Statistics. We focus on the area in Italy that experienced the initial outbreak of COVID-19 and estimated a Bayesian model fitting age-stratified mortality data from 2020 and previous years. We also assessed the sensitivity of our estimates to alternative assumptions on the proportion of population infected. Findings: We estimate an overall infection fatality rate of 1.29% (95% credible interval [CrI] 0.89 - 2.01), as well as large differences by age, with a low infection fatality rate of 0.05% for under 60 year old (CrI 0-.19) and a substantially higher 4.25% (CrI 3.01-6.39) for people above 60 years of age. In our sensitivity analysis, we found that even under extreme assumptions, our method delivered useful information. For instance, even if only 10% of the population were infected, the infection fatality rate would not rise above 0.2% for people under 60. Interpretation: Our empirical estimates based on population level data show a sharp difference in fatality rates between young and old people and firmly rule out overall fatality ratios below 0.5% in populations with more than 30% over 60 years old.", "qid": 21, "docid": "86l1xixa", "rank": 50, "score": 6.950399875640869}, {"content": "Title: The overall mortality caused by COVID-19 in the European region is highly associated with demographic composition: A spatial regression-based approach Content: The demographic factors have a substantial impact on the overall casualties caused by the COVID-19. In this study, the spatial association between the key demographic variables and COVID-19 cases and deaths were analyzed using the spatial regression models. Total 13 (for COVID-19 case factor) and 8 (for COVID-19 death factor) key variables were considered for the modelling. Total five spatial regression models such as Geographically weighted regression (GWR), Spatial Error Model (SEM), Spatial Lag Model (SLM), Spatial Error_Lag model (SEM_SLM), and Ordinary Least Square (OLS) were performed for the spatial modelling and mapping of model estimates. The local R2 values, which suggesting the influences of the selected demographic variables on overall casualties caused by COVID-19, was found highest in Italy and the UK. The moderate local R2 was observed for France, Belgium, Netherlands, Ireland, Denmark, Norway, Sweden, Poland, Slovakia, and Romania. The lowest local R2 value for COVID-19 cases was accounted for Latvia and Lithuania. Among the 13 variables, the highest local R2 was calculated for total population (R2 = 0.92), followed by death crude death rate (R2 = 0.9), long time illness (R2 = 0.84), population with age>80 (R2 = 0.59), employment (R2 = 0.46), life expectancy at 65 (R2 = 0.34), crude birth rate (R2 = 0.31), life expectancy (R2 = 0.31), Population with age 65-80 (R2 = 0.29), Population with age 15-24 (R2 = 0.27), Population with age 25-49 (R2 = 0.27), Population with age 0-14 (R2 = 0.23), and Population with age 50-65 (R2 = 0.23), respectively.", "qid": 21, "docid": "pil10k4i", "rank": 51, "score": 6.948500156402588}, {"content": "Title: On case-fatality rate: review and hypothesis. Content: The relationship between log cumulative number of patients (X) and that of deaths (Y) in an epidemic follows the equation logY = klogX - klogN(0), where k is a constant determining the slope and N(0) is the value of X when Y = 1. Diseases with k = 1 are Ebola hemorrhagic fever, avian influenza H5N1, cholera, and hand, foot, and mouth disease; those with k > 1 are the influenza H1N1 2009 pandemic in countries other than Mexico and the SARS epidemic in some countries; and those with k < 1 include the influenza H1N1 2009 pandemic in Mexico. Epidemics with k > 1 can be simulated by postulating two subpopulations (normal population [NP] and vulnerable population [VP]), where the epidemic proceeds at higher speed and at higher mortality in VP than in NP. Epidemics with k < 1 can be simulated by postulating coexisting high virulence virus (HVV) and low virulence virus (LVV), with the former being propagated at slower speed and with a higher mortality rate than the latter. An epidemic with k > 1 was simulated using parameters that are fractions of subpopulations NP or VP from the total population (f) and NP- or VP-specific patient multiplication (M) and mortality (D) rates. An epidemic with k < 1 was simulated using parameters that are fractions of HVV- or LVV-infected human populations (f), and HVV- or LVV-specific M and D.", "qid": 21, "docid": "h0plbvg3", "rank": 52, "score": 6.946300029754639}, {"content": "Title: Trends in Infectious Disease Mortality, South Korea, 1983\u20132015 Content: We used national statistics from 1983\u20132015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies.", "qid": 21, "docid": "osyoizng", "rank": 53, "score": 6.938899993896484}, {"content": "Title: Differential mortality in COVID-19 patients from India and western countries Content: BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as \u2018COVID-19\u2019, \u2018Pandemics\u2019, \u2018disease outbreaks\u2019 and \u2018India\u2019 on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.", "qid": 21, "docid": "q3pqo3iu", "rank": 54, "score": 6.916600227355957}, {"content": "Title: Differential mortality in COVID-19 patients from India and western countries Content: BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'Pandemics', 'disease outbreaks' and 'India' on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.", "qid": 21, "docid": "v4yto9p3", "rank": 55, "score": 6.916599273681641}, {"content": "Title: Age- and Sex-Specific Risk Profiles and In-Hospital Mortality in 13,932 Spanish Stroke Patients. Content: BACKGROUND In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. METHODS We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality. RESULTS The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively. CONCLUSION Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.", "qid": 21, "docid": "8g3vfjka", "rank": 56, "score": 6.910399913787842}, {"content": "Title: Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma. Content: BACKGROUND The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC). OBJECTIVE Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC. DESIGN, SETTING, AND PARTICIPANTS A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m(2), albumin <3.5 g/dl, or preoperative weight loss \u2265 5% of body weight. INTERVENTION All patients underwent radical or partial nephrectomy. MEASUREMENTS Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method. RESULTS AND LIMITATIONS Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p<0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40-4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17-6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature. CONCLUSIONS ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.", "qid": 21, "docid": "f15uh4id", "rank": 57, "score": 6.886899948120117}, {"content": "Title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID-19 pandemic Content: BACKGROUND: Data on the development of Covid-19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017-2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID-care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID-cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID-specific causes. CONCLUSIONS: During the 2017-2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.", "qid": 21, "docid": "hdfn60bt", "rank": 58, "score": 6.885499954223633}, {"content": "Title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID\u201019 pandemic Content: BACKGROUND: Data on the development of Covid\u201019 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017\u20132018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID\u2010care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID\u2010cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID\u2010specific causes. CONCLUSIONS: During the 2017\u20132018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.", "qid": 21, "docid": "rmcsjck3", "rank": 59, "score": 6.885499000549316}, {"content": "Title: The projected impact of mitigation and suppression strategies on the COVID-19 epidemic in Senegal: A modelling study Content: Background: Physical distancing measures that reduce social contacts have formed a key part of national COVID-19 containment and mitigation strategies. Many Sub-Saharan African nations are now facing increasing numbers of cases of COVID-19 and there is a need to understand what levels of measures may be required to successfully reduce transmission. Methods: We collated epidemiological data along with information on key COVID-19 specific response policies and health system capacity estimates for services needed to treat COVID-19 patients in Senegal. We calibrated an age-structured SEIR model to these data to capture transmission dynamics accounting for demography, contact patterns, hospital capacity and disease severity. We simulated the impact of mitigation and suppression strategies focussed on reducing social contact rates. Results: Senegal acted promptly to contain the spread of SARS-CoV-2 and as a result has reduced the reproduction number from 1.9 (95% CI 1.7-2.2) to 1.3 (95% CI 1.2-1.5), which has slowed but not fully interrupted transmission. We estimate that continued spread is likely to peak in October, and to overwhelm the healthcare system with an estimated 77,400 deaths(95% CI 55,270-100,700). Further reductions in contact rates to suppress transmission (Rt<1) could significantly reduce this burden on healthcare services and improve overall health outcomes. Conclusions: Our results demonstrate that Senegal has already significantly reduced transmission. Enhanced physical distancing measures and rapid scale up of hospital capacity is likely to be needed to reduce mortality and protect healthcare infrastructure from high levels of demand.", "qid": 21, "docid": "x40l8ljx", "rank": 60, "score": 6.863500118255615}, {"content": "Title: Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Content: RAPID COMMUNICATION 22 March 2020 Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Background: The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods: Using population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged \u226530 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings: 20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged \u226470 years with \u22651 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of \u22652 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with \u22653 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population (do-nothing), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. Interpretation: We provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected (do nothing) scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.", "qid": 21, "docid": "11hi1jel", "rank": 61, "score": 6.85890007019043}, {"content": "Title: Incidence of cervical cancer and age-specific survival of small cell cervical carcinoma in Taiwan. Content: OBJECTIVE To determine the incidence of cervical cancer and the age-specific survival from small cell cervical carcinoma in Taiwan. DESIGN Retrospective study. Setting. Taiwan. POPULATION Women diagnosed with cervical cancer from 1991 to 2005. METHODS Analysis of data from the National Cancer Registration System and National Death Certification System. MAIN OUTCOME MEASURES Incidence and age at diagnosis of cervical carcinoma and age-specific and overall survival from small cell cervical carcinoma. RESULTS During the study period, 36 122 women were diagnosed with cervical cancer, and 81.8% had squamous cell carcinoma (SCC). For the periods 1991-1995, 1996-2000 and 2001-2005, the mean age at diagnosis increased from 53.9 \u00b1 13.3 to 55.0 \u00b1 14.9 and then to 56.7 \u00b1 14.7 years, respectively. The incidence of SCC decreased from 1991 to 2005. During the same period, non-significant increases of adenocarcinoma and small cell carcinoma were noted. For SCC, occurrence peaked in 1991-1995 in patients 50-59 years of age. From 1996 to 2005, it peaked in patients 40-49 years of age. For cervical adenocarcinoma, occurrence peaked in patients 40-49 years of age, with a steady increase in this age group from 1991 to 2005. Occurrence of small cell cervical carcinoma peaked in the period 1991-1995 in patients 30-39 years of age. During the 15 years of the study, the overall mortality rate of the 198 patients with small cell cervical carcinoma was 65.7%. CONCLUSIONS In Taiwan, the incidence of small cell cervical carcinoma and adenocarcinoma tended to increase, but the incidence of squamous cell cervical carcinoma significantly decreased during the period 1991-2005.", "qid": 21, "docid": "n1iy1n7h", "rank": 62, "score": 6.854599952697754}, {"content": "Title: Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination Content: BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3735-7) contains supplementary material, which is available to authorized users.", "qid": 21, "docid": "dk4snw9r", "rank": 63, "score": 6.839099884033203}, {"content": "Title: Epidemiology of the 2020 pandemic of COVID\u201019 in the state of Georgia: Inadequate critical care resources and impact after 7 weeks of community spread Content: OBJECTIVES: Novel coronavirus (COVID\u201019) is a global pandemic currently spreading rapidly across the United States. We provide a comprehensive look at COVID\u201019 epidemiology across the state of Georgia, which includes vast rural communities that may be disproportionately impacted by the spread of this infectious disease. METHODS: All 159 Georgia counties were included in this study. We examined the geographic variation of COVID\u201019 in Georgia from March 3 through April 24, 2020 by extracting data on incidence and mortality from various national and state datasets. We contrasted county\u2010level mortality rates per 100,000 population (MRs) by county\u2010level factors. RESULTS: Metropolitan Atlanta had the overall highest number of confirmed cases; however, the southwestern rural parts of Georgia, surrounding the city of Albany, had the highest bi\u2010weekly increases in incidence rate. Among counties with >10 cases, MRs were highest in the rural counties of Randolph (233.2), Terrell (182.5), Early (136.3), and Dougherty (114.2). Counties with the highest MRs (22.5\u20132332 per 100,000) had a higher proportion of: non\u2010Hispanic Blacks residents, adults aged 60+, adults earning <$20,000 annually, and residents living in rural communities when compared with counties with lower MRs. These counties also had a lower proportion of the population with a college education, lower number of ICU beds per 100,000 population, and lower number of primary care physicians per 10,000 population. CONCLUSIONS: While urban centers in Georgia account for the bulk of COVID\u201019 cases, high mortality rates and low critical care capacity in rural Georgia are also of critical concern.", "qid": 21, "docid": "ynpqzu5l", "rank": 64, "score": 6.829999923706055}, {"content": "Title: Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19 Content: Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.", "qid": 21, "docid": "4f6h7agt", "rank": 65, "score": 6.7932000160217285}, {"content": "Title: Urban Air Pollution May Enhance COVID-19 Case-Fatality and Mortality Rates in the United States Content: BACKGROUND: The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 240,000 lives worldwide, causing tremendous public health, social, and economic damages. While the risk factors of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis. METHODS: We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010\u20132016) county-level exposures to NO(2), PM(2.5) and O(3) and county-level COVID-19 case-fatality and mortality rates in the US. We used both single and multipollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level healthcare capacity, phase-of-epidemic, population mobility, sociodemographic, socioeconomic status, behavior risk factors, and meteorological factors. RESULTS: 1,027,799 COVID-19 cases and 58,489 deaths were reported in 3,122 US counties from January 22, 2020 to April 29, 2020, with an overall observed case-fatality rate of 5.8%. Spatial variations were observed for both COVID-19 death outcomes and long-term ambient air pollutant levels. County-level average NO(2) concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models (p-values<0.05). Per inter-quartile range (IQR) increase in NO(2) (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 7.1% (95% CI 1.2% to 13.4%) and 11.2% (95% CI 3.4% to 19.5%), respectively. We did not observe significant associations between long-term exposures to PM(2.5) or O(3) and COVID-19 death outcomes (p-values>0.05), although per IQR increase in PM(2.5) (3.4 ug/m(3)) was marginally associated with 10.8% (95% CI: \u22121.1% to 24.1%) increase in COVID-19 mortality rate. DISCUSSIONS AND CONCLUSIONS: Long-term exposure to NO(2), which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM(2.5) and O(3) exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO(2) levels. Moreover, continuation of current efforts to lower traffic emissions and ambient air pollution levels may be an important component of reducing population-level risk of COVID-19 deaths.", "qid": 21, "docid": "14ftgh6k", "rank": 66, "score": 6.789400100708008}, {"content": "Title: Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study Content: Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.", "qid": 21, "docid": "92ipp5ge", "rank": 67, "score": 6.786900043487549}, {"content": "Title: Cefepime Efficacy and Safety in Children: A Systematic Review and Meta-analysis. Content: Background Cefepime is a fourth-generation cephalosporin antibiotic used to treat a variety of infections. The US Food and Drug Administration approved its use in certain types of infections among pediatric patients, and yet there have been mixed data about its efficacy and safety in this population. Objective The objective of this review is to compare efficacy and all-cause mortality of cefepime to other clinically indicated antibiotics among children. Methods We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, LILACS, and clinicaltrials.gov databases through February 8, 2016. We included randomized controlled trials comparing cefepime to other clinical antibiotics, placebo, or no treatment in children aged 0-19 years in the inpatient setting with clinical signs of infection. The primary outcome of interest was all-cause mortality. The secondary outcomes were success rate, treatment failure, and incidence of adverse events. Study quality was assessed using the Cochrane Risk of Bias Assessment Tool. Results Seventeen studies met the inclusion criteria. There was a total of 1,285 participants included, 624 participants in the cefepime arm and 661 in the comparison arm. A random effects meta-analysis for all-cause mortality showed no difference in rates of mortality between cefepime and comparator antibiotics with a mortality risk ratio of 0.88 (95% CI: 0.71-1.08). For the secondary outcomes of success rate and treatment failure, a random effects model meta-analysis conducted of the studies showed no difference in rate between cefepime and comparator antibiotics with an overall risk ratio of 0.98 (95% CI: 0.92-1.05) and 1.04 (95% CI: 0.91-1.19), respectively. Adverse events were not statistically assessed given widespread heterogeneity. Overall, the studies had unclear risk of bias and were limited by high heterogeneity and methodological flaws. Conclusion The efficacy and safety of cefepime in pediatric patients remain unclear despite the inclusion of newer trials since the last index systematic review conducted a decade ago.", "qid": 21, "docid": "bgptydsb", "rank": 68, "score": 6.776000022888184}, {"content": "Title: Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S. Content: Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.", "qid": 21, "docid": "0j6a5xqc", "rank": 69, "score": 6.761000156402588}, {"content": "Title: The effect of public health measures on the 1918 influenza pandemic in U.S. cities. Content: During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10-30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30-50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.", "qid": 21, "docid": "6ulvk9hv", "rank": 70, "score": 6.7418999671936035}, {"content": "Title: Association of BCG vaccination policy with prevalence and mortality of COVID-19 Content: There is some evidence that tuberculosis vaccine bacillus Calmette-Gu\u00e9rin (BCG) has non-specific beneficial effects against non-related infections. Here, we examined the possible association between BCG vaccination with prevalence and mortality by COVID-19 by using publicly available data of COVID-19 in 199 countries/regions and the BCG World Atlas. By using linear regression modeling, we found that the number of total cases and deaths per one million population were significantly associated with the country's policy concerning BCG vaccine administration. The amount of variance in cases and deaths explained by BCG vaccination policy ranged between 12.5% and 38%. Importantly, this effect remained significant after controlling for the country's life expectancy and the average temperature in February and March 2020, which themselves are significantly correlated with the cases and deaths indices, respectively. By contrast, the ratio between deaths and cases was weakly affected. This latter outcome suggested that BCG vaccination may have hindered the overall spread of the virus or progression of the disease rather than reducing mortality rates (i.e., deaths/cases ratio). Finally, by roughly dividing countries into three categories showing high, middle, or low growth rate of the cases, we found a highly significant difference between the slope categories among the BCG groups, suggesting that the time since the onset of the spread of the virus was not a major confounding factor. While this study potentially suffers from a number of unknown confounding factors, these associations support the idea that BCG vaccination may provide protection against SARS-CoV-2, which, together with its proven safety, encourages consideration of further detailed epidemiological studies, large-scale clinical trials on the efficacy of this vaccine on COVID-19, and/or re-introduction of BCG vaccination practice in the countries which are currently devoid of the practice.", "qid": 21, "docid": "93b2ivio", "rank": 71, "score": 6.731200218200684}, {"content": "Title: High-Frequency Oscillatory Ventilation in Pediatric Acute Hypoxemic Respiratory Failure: Disease-Specific Morbidity Survival Analysis Content: BACKGROUND: Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity. METHODS: A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality. RESULTS: A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05). CONCLUSION: High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.", "qid": 21, "docid": "8od8vhob", "rank": 72, "score": 6.718500137329102}, {"content": "Title: COVID-19: Modelling Local Transmission and Morbidity effects to provide an estimate of overall Relative Healthcare Resource Impact by General Practice Granularity Content: Introduction Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus that has not been previously identified in humans. Methods Two key factors were analysed which when multiplied together would give an estimate of relative demand on healthcare utilisation. These factors were case incidence and case morbidity. GP Practice data was used as this provided the most geographically granular source of published public population data. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, % age >16 at fulltime work/education, % age over 60, % BME ethnicity, social deprivation as IMD 2019, Location as latitude/longitude, and patient engagement as % self-confident in their own long term condition management. Average case morbidity was calculated by applying the international mortality Odds Ratio to the local population relevant age and disease prevalences and then summing and dividing by the equivalent national figure. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. Results The case incidence regression is a dynamic situation with the significance of specific factors moderating over time as the balance between external infection, community transmission and impact of mitigation measures feeds through to the number of cases. It showed that currently Urban, % Working and age >60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative HC impact was wide with 80% of practices falling between 20%-250% of the national median. Once practice population numbers were included it showed that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. Conclusion Covid-19 is impacting on the utilisation of health and social care resources across the country. This model provides a method for predicting relative local levels of disease burden based on defined criteria and thereby providing a method for targeting limited (and perhaps soon to be scarce) care resources to optimise national, regional and local responses to the COVID-19 outbreak.", "qid": 21, "docid": "5242ns8i", "rank": 73, "score": 6.706999778747559}, {"content": "Title: A population-based analysis of emergent versus elective paraesophageal hernia repair using the Nationwide Inpatient Sample. Content: BACKGROUND As the life expectancy in the United States continues to increase, more elderly, sometimes frail patients present with sub-acute surgical conditions such as a symptomatic paraesophageal hernia (PEH). While the outcomes of PEH repair have improved largely due to the proliferation of laparoscopic surgery, there is still a defined rate of morbidity and mortality. We sought to characterize the outcomes of both elective and emergent PEH repair using a large population-based data set. METHODS The Nationwide Inpatient Sample was queried for primary ICD-9 codes associated with PEH repair (years 2006-2008). Outcomes were in-hospital mortality and the occurrence of a pre-identified complication. Multivariate analysis was performed to determine the risk factors for complications and mortality following both elective and emergent PEH repair. RESULTS A total of 8,462 records in the data, representing 41,723 patients in the US undergoing PEH repair in the study interval, were identified. Of these procedures, 74.2% was elective and 42.4% was laparoscopic. The overall complication and mortality rates were 20.8 and 1.1%, respectively. Emergent repair was associated with a higher rate of morbidity (33.4 vs. 16.5%, p < 0.001) and mortality (3.2 vs. 0.37%, p < 0.001) than elective repair. Emergent repair patients were more likely to be male, were older, and more likely to be minority. Logistic modeling revealed that younger age, elective case status, and a laparoscopic approach were independently associated with a lower probability of complications and mortality. CONCLUSIONS Patients undergoing emergent PEH repair in the United States tend to be older, more likely a racial minority, and less likely to undergo laparoscopic repair. Elective repair, younger age, and a laparoscopic approach are associated with improved outcomes. Considering all of the above, we recommend that patients consider elective repair with a surgeon experienced in the laparoscopic approach, especially when symptoms related to the hernia are present.", "qid": 21, "docid": "ejrcf63p", "rank": 74, "score": 6.704800128936768}, {"content": "Title: Long-Term Survival after Radiofrequency Ablation of Lung Oligometastases from Five Types of Primary Lesions: A Retrospective Evaluation. Content: PURPOSE To conduct a retrospective evaluation of long-term survival after radiofrequency (RF) ablation for lung oligometastases from 5 types of primary lesions. MATERIALS AND METHODS The study population consisted of 123 patients with lung oligometastases from colorectal cancer (CRC), non-small-cell lung cancer, hepatocellular carcinoma, esophageal cancer, and renal-cell carcinoma treated with RF ablation. Lung oligometastases were defined as 1-5 metastases confined to the lung while the primary cancer and other metastases were eradicated. Overall survival (OS) and recurrence-free survival (RFS) were estimated for the overall study population and for patients with each type of primary lesion. The OS and RFS rates were compared with those of the patients with any of the other four primary lesion types. Finally, various variables were analyzed to determine what factors influenced OS and RFS. RESULTS The median follow-up was 45.7 months, and the 5-year OS and RFS rates for all 123 patients were 62% and 25%, respectively. The OS time for patients with metastases from CRC was significantly longer (P = .042); it was significantly shorter (P = .022) in patients with metastases from esophageal cancer. Longer disease-free interval was significantly (P = .015) associated with better OS. There was no variable significantly associated with OS and RFS on multivariate analyses. CONCLUSIONS Data from this single-center study appear promising in terms of long-term survival after RF ablation of lung oligometastases from 5 primary lesions.", "qid": 21, "docid": "9ru3gzdc", "rank": 75, "score": 6.70389986038208}, {"content": "Title: Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients Content: BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women\u2019s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient\u2019s CXR was assigned an opacification score of 0\u20134 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score\u2019s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05\u20131.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07\u20131.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04\u20131.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02\u20131.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient\u2019s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.", "qid": 21, "docid": "b5s67twk", "rank": 76, "score": 6.694699764251709}, {"content": "Title: Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis. Content: In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).", "qid": 21, "docid": "0wyn97y9", "rank": 77, "score": 6.6819000244140625}, {"content": "Title: Systematic review on the outcomes of poller screw augmentation in intramedullary nailing of long bone fracture. Content: Various technical tips have been described on the placement of poller screws during intramedullary (IM) nailing; however studies reporting outcomes are limited. Overall there is no consistent conclusion about whether intramedullary nailing alone, or intramedullary nails augmented with poller screws is more advantageous.We conducted a systematic review of PubMed, EMBASE, and Cochrane databases. Seventy-five records were identified, of which 13 met our inclusion criteria. In a systematic review we asked: (1) What is the proportion of nonunions with poller screw usage? (2) What is the proportion of malalignment, infection and secondary surgical procedures with poller screw usage? The overall outcome proportion across the studies was computed using the inverse variance method for pooling.Thirteen studies with a total of 371 participants and 376 fractures were included. Mean follow-up time was 21.1 months. Mean age of included patients was 40.0 years. Seven studies had heterogenous populations of nonunions and acute fractures. Four studies included only acute fractures and two studies examined nonunions only.The results of the present systematic review show a low complication rate of IM nailing augmented with poller screws in terms of nonunion (4%, CI: 0.03-0.07), coronal plane malunion (5%, CI: 0.03-0.08), deep (5%, CI: 0.03-0.11) and superficial (6%, CI: 0.03-0.11) infections, and secondary procedures (8%, CI: 0.04-0.18).When compared with the existing literature our review suggests intramedullary nailing with poller screws has lower rates of nonunion and coronal malalignment when compared with nailing alone. Prospective randomized control trial is necessary to fully determine outcome benefits. Cite this article: EFORT Open Rev 2020;5:189-203. DOI: 10.1302/2058-5241.5.190040.", "qid": 21, "docid": "r6ks279o", "rank": 78, "score": 6.6803998947143555}, {"content": "Title: The effects of environmental stressors on the mortality of the oldest old male population in Hong Kong, 1977-2006. Content: Although age-sex-specific mortality rates were decreasing over the years, such a trend was not observed for the male population aged 85 or above (the oldest old) in Hong Kong. Despite literature suggesting that environmental stressors were associated with higher mortality, the adverse effects of socioeconomic and political events were seldom included. Hence, this study explored the relationship between environmental stressors covering adverse weather conditions as well as key socioeconomic and political events and fluctuations in the oldest old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old mortality rates in Hong Kong were observed to have a likelihood of being associated with these environmental stressors. Furthermore, men appeared to be more susceptible to these risk factors than did women. More care and attention should be given to the oldest old men, in particular, during periods of socioeconomic or political upheavals. A cohort study would be useful to study these stressors in greater detail.", "qid": 21, "docid": "l855jlqu", "rank": 79, "score": 6.6793999671936035}, {"content": "Title: Molecular diagnosis of infectious diseases in S\u00e3o Miguel Island (Azores, Portugal): A hospital-based descriptive study. Content: INTRODUCTION We performed a descriptive analysis of molecular diagnosis of infectious agents in the S\u00e3o Miguel Island population, in order to address questions like what is the frequency of clinical requests, is it observable seasonality of pathogens, and what is the positive rate for the clinical diagnosis. METHODOLOGY This was a retrospective and descriptive study based on 878 individuals suspected of harboring infectious diseases during two consecutive years, 2012-2013. More than 25 different pathogens were investigated by polymerase chain reaction (PCR)-based methods. The individuals were stratified into gender, occupation, and age groups. RESULTS The pathogen with more clinical requests was hepatitis C virus, investigated in 225 individuals (30.0%), followed by Leptospira spp., in 187 (24.9%). Overall, data demonstrated a gender distribution bias, where 72.9% of cases were males. The age group of 25 to 44 years was the class with more clinical requests. Regarding occupation, a predominance of construction workers (12.0%) was observed, followed by retired workers (11.0%). Patient distribution per year showed a higher number of patients in the fall months. Diagnoses of leptospirosis and respiratory virus infections presented seasonality. CONCLUSIONS The present study provides a valid contribution to the knowledge of the epidemiology of infectious diseases in the S\u00e3o Miguel Island (Azores, Portugal) population.", "qid": 21, "docid": "poh6if0r", "rank": 80, "score": 6.67549991607666}, {"content": "Title: Burden and changes in HIV/AIDS morbidity and mortality in Southern Africa Development Community Countries, 1990\u20132017 Content: BACKGROUND: The 16 Southern Africa Development Community (SADC) countries remain the epicentre of the HIV/AIDS epidemic with the largest number of people living with HIV/AIDS. Anti-retroviral treatment (ART) has improved survival and prevention of mother-to-child transmission (PMTCT) of HIV, but the disease remains a serious cause of mortality. We conducted a descriptive epidemiological analysis of HIV/AIDS burden for the 16 SADC countries using secondary data from the Global Burden of Diseases, Injuries and Risk Factor (GBD) Study. METHODS: The GBD study is a systematic, scientific effort by the Institute for Health Metrics and Evaluation (IHME) to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. We analyzed the following outcomes: mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to HIV/AIDS for SADC. Input data for GBD was extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service utilisation, disease notifications, and other sources. Country- and cause-specific HIV/AIDS-related death rates were calculated using the Cause of Death Ensemble model (CODEm) and spatiotemporal Gaussian process regression (ST-GPR). Deaths were multiplied by standard life expectancy at each age-group to calculate YLLs. Cause-specific mortality was estimated using a Bayesian meta-regression modelling tool, DisMod-MR. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases to calculate YLDs. Crude and age-adjusted rates per 100,000 population and changes between 1990 and 2017 were determined for each country. RESULTS: In 2017, HIV/AIDS caused 336,175 deaths overall in SADC countries, and more than 20 million DALYs. This corresponds to a 3-fold increase from 113,631 deaths (6,915,170 DALYs) in 1990. The five leading countries with the proportion of deaths attributable to HIV/AIDS in 2017 were Botswana at the top with 28.7% (95% UI; 23.7\u201335.2), followed by South Africa 28.5% (25.8\u201331.6), Lesotho, 25.1% (21.2\u201330.4), eSwatini 24.8% (21.3\u201328.6), and Mozambique 24.2% (20.6\u201329.3). The five countries had relative attributable deaths that were at least 14 times greater than the global burden of 1.7% (1.6\u20131.8). Similar patterns were observed with YLDs, YLLs, and DALYs. Comoros, Seychelles and Mauritius were on the lower end, with attributable proportions less than 1%, below the global proportion. CONCLUSIONS: Great progress in reducing HIV/AIDS burden has been achieved since the peak but more needs to be done. The post-2005 decline is attributed to PMTCT of HIV, resources provided through the US President\u2019s Emergency Plan For AIDS Relief (PEPFAR), and behavioural change. The five countries with the highest burden of HIV/AIDS as measured by proportion of death attributed to HIV/AIDS and age-standardized mortaility rate were Botswana, South Africa, Lesotho, eSwatini, and Mozambique. SADC countries should cooperate, work with donors, and embrace the UN Fast-Track approach, which calls for frontloading investment from domestic or other sources to prevent and treat HIV/AIDS. Robust tracking, testing, and early treatment are required, as well as refinement of individual treatment strategies for transient individuals in the region.", "qid": 21, "docid": "hs9cfdsu", "rank": 81, "score": 6.669400215148926}, {"content": "Title: How many lives can be saved? A global view on the impact of testing, herd immunity and demographics on COVID-19 fatality rates Content: In this work, we assess the global impact of COVID-19 showing how demographic factors, testing policies and herd immunity are key for saving lives. We extend a standard epidemiological SEIR model in order to: (a) identify the role of demographics (population size and population age distribution) on COVID-19 fatality rates; (b) quantify the maximum number of lives that can be saved according to different testing strategies, different levels of herd immunity, and specific population characteristics; and (d) infer from the observed case fatality rates (CFR) what the true fatality rate might be. Different from previous SEIR model extensions, we implement a Bayesian Melding method in our calibration strategy which enables us to account for data limitation on the total number of deaths. We derive a distribution of the set of parameters that best replicate the observed evolution of deaths by using information from both the model and the data.", "qid": 21, "docid": "2epo3a4r", "rank": 82, "score": 6.634200096130371}, {"content": "Title: Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Content: We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received \u22651 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was \u22654 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.", "qid": 21, "docid": "rzj773h8", "rank": 83, "score": 6.63070011138916}, {"content": "Title: Untangling factors associated with country-specific COVID-19 incidence, mortality and case fatality rates during the first quarter of 2020 Content: At early stages of the COVID-19 pandemic which we are experiencing, the publicly reported incidence, mortality and case fatality rates (CFR) vary significantly between countries. Here we aim to untangle factors that are associated with the differences during the first quarter of the year 2020. Number of performed COVID-19 tests has a strong correlation with country-specific incidence (p <2\u00d710-16) and mortality rate (p = 5.1\u00d710-8). Using multivariate linear regression we show that incidence and mortality rates correlate significantly with GDP per capita (p = 2.6\u00d710-15 and 7.0\u00d710-4, respectively), country-specific duration of the outbreak (2.6\u00d710-4 and 0.0019), fraction of citizens over 65 years old (p = 0.0049 and 3.8\u00d710-4) and level of press freedom (p = 0.021 and 0.019) which cumulatively explain 80% of variability of incidence and more than 60% of variability of mortality of the disease during the period analyzed. Country hemisphere demonstrated significant correlation only with mortality (p = 0.17 and 0.036) whereas population density (p = 0.94 and p = 0.75) and latitude (p = 0.61 and 0.059) did not reach significance in our model. Case fatality rate is shown to rise as the outbreak progresses (p = 0.028). We rank countries by COVID-19 mortality corrected for incidence and the factors that were shown to affect it, and by CFR corrected for outbreak duration, yielding very similar results. Among the countries where the outbreak started after the 15th of February and with at least 1000 registered patients during the period analyzed, the lowest corrected CFR are seen in Israel, South Africa and Chile. The ranking results should be considered with caution as they do not consider all confounding factors or data reporting biases.", "qid": 21, "docid": "huyl21vz", "rank": 84, "score": 6.6097002029418945}, {"content": "Title: Microvascular Disease Confers Additional Risk to COVID-19 Infection Content: The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin \u201cCOVID-19 Clinical Guidance for the CV Care Team\u201d, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% \u226580 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention. MVD And COVID Abstract The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) results in COVID-19 which can lead to severe illness and death. The majority of fatalities thus far in the pandemic have been attributed to pneumonia. The overall mortality risk reported as of March 28, 2020 varies from 2.3% in China, 2.7% in Iran, and 0.5% in South Korea. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin \u201cCOVID-19 Clinical Guidance for the CV Care Team\u201d, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79; 14.8% \u226580), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a reason for the higher mortality risk in these populations that is not apparent. We further present a set of pathophysiological reasons for the heightened danger could lead to therapies for enhanced management and prevention.", "qid": 21, "docid": "cmcv1k62", "rank": 85, "score": 6.601500034332275}, {"content": "Title: Comparative use of the Ages and Stages Questionnaires in the USA and Scandinavia: a systematic review. Content: AIM The aim of this systematic review was to investigate screening practices with the Ages and Stages Questionnaires (ASQ) and the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) in the USA and Scandinavia and to identify practical lessons and research opportunities. METHOD The review was performed for ASQ- and ASQ:SE-related studies in children from birth to 5 years. From nine databases and 1689 references (published from 1988-2018), 127 articles were included and categorized using Covidence online software. The Critical Appraisal Skills Programme Checklists were used before data synthesis. RESULTS US studies primarily use the ASQ/ASQ:SE to detect delays in general and at-risk populations in medical settings, which increases early detection, clinician-referral, and intervention rates. Scandinavian studies commonly use the ASQ/ASQ:SE to monitor developmental-behavioural differences in intervention/exposure-based cohorts. Pre-visit screening yields completion/return rates of 83% to more than 90% and fosters same-day interpretation. When referrals are indicated, systemwide care coordination or colocation with a developmental-behavioural specialist is beneficial. INTERPRETATION Practical implementation lessons are reviewed. Research opportunities include investigating and measuring the ASQ/ASQ:SE's 'overall' sections. Danish, Norwegian, and Swedish translations are available but up-to-date norming and validation studies are needed throughout Scandinavia. Randomized controlled trials are needed to investigate outcomes in screened versus unscreened cohorts. WHAT THIS PAPER ADDS General and at-risk populations broadly benefited from periodic Ages and Stages Questionnaires (ASQ) and/or Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) screening. Pre-visit ASQ and/or ASQ:SE screenining implementation systems work best. The ASQ and ASQ:SE 'overall' sections are not quantifiable and under-researched.", "qid": 21, "docid": "zj2ihmgb", "rank": 86, "score": 6.590199947357178}, {"content": "Title: Health impact of hospital restrictions on seriously ill hospitalized patients: lessons from the Toronto SARS outbreak. Content: BACKGROUND Restrictions on non-urgent hospital care imposed to control the 2003 Toronto severe acute respiratory syndrome outbreak led to substantial disruptions in hospital clinical practice, admission, and transfer patterns. OBJECTIVES We assessed whether there were unintended health consequences to seriously ill hospitalized patients. STUDY DESIGN, SETTING, AND POPULATION: Population-based longitudinal cohort study of patients residing in Toronto or an urban control region with an incident admission for 1 of 7 serious conditions in the 3 years before, or the 4 months during or after restrictions. OUTCOME MEASURES Short-term mortality, overall readmissions, cardiac readmissions for acute myocardial infarction patients, serious complications for very low birth weight babies, and quality of care measures, comparing adjusted rates across time periods within regions. RESULTS Mortality, readmission, and complication rates did not change for any condition during or after severe acute respiratory syndrome restrictions. Although rates of invasive cardiac procedures for acute myocardial infarction patients decreased 11-37% in Toronto, rates of nonfatal cardiac outcomes did not change. CONCLUSIONS Restrictions on non-urgent hospital utilization and hospital transfers may be a safe public health strategy to employ to control nosocomial outbreaks or provide hospital surge capacity for up to several months, in large, well-developed healthcare systems with good availability of community-based care.", "qid": 21, "docid": "ou7o700t", "rank": 87, "score": 6.569799900054932}, {"content": "Title: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy Content: PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999\u20132006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280\u20131,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.", "qid": 21, "docid": "j5p5mtiq", "rank": 88, "score": 6.569200038909912}, {"content": "Title: Controlled Avalanche: A Regulated Voluntary Exposure Approach for Addressing Covid19 Content: Background: The ongoing Covid-19 pandemic has driven many countries to take radical suppression measures. While reducing mortality, these measures result in severe economic repercussions, and inhibit the development of herd immunity. Until an effective vaccine will be available, we propose an alternative approach, akin to avalanche control at ski resorts, a practice which intentionally triggers small avalanches in order to prevent a singular catastrophic one. Its main goal is to approach herd immunity faster than the current alternatives, with lower mortality rates and lower demand for critical health-care resources. According to this approach, individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued 'immunity certificates' if they are confirmed to have developed SARS-CoV-2 antibodies. Methods: Using a compartmental model we examine the implications of the controlled avalanche (CA) strategy over the population in Israel. We compare four scenarios: in two scenarios the CA program is applied to the low-risk population (with the rest of the population subject to mitigation measures), followed by mitigation for the entire population or by uncontrolled spread. These are compared to mitigated and uncontrolled scenarios without the CA program. We discuss the economic, ethical and public health implications of the CA strategy. Findings: We show that compared to mitigation of the entire population, the CA strategy reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62% and decreases the time required for release of 50% of the low-risk population by more than 2 months. Interpretation: This study suggests an ethically acceptable practice, that enables reaching herd immunity faster than the current alternatives, with low mortality and minimal economic damage.", "qid": 21, "docid": "6k4brmx2", "rank": 89, "score": 6.5680999755859375}, {"content": "Title: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe Content: COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (\u2265 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population \u2265 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = \u22120.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.", "qid": 21, "docid": "9p0dsyqx", "rank": 90, "score": 6.5559000968933105}, {"content": "Title: Urban Scaling of COVID-19 epidemics Content: Susceptible-Invective-Recovered (SIR) mathematical models are in high demand due to the COVID-19 pandemic. They are used in their standard formulation, or through the many variants, trying to fit and hopefully predict the number of new cases for the next days or weeks, in any place, city, or country. Such is key knowledge for the authorities to prepare for the health systems demand or to apply restrictions to slow down the infectives curve. Even when the model can be easily solved ---by the use of specialized software or by programming the numerical solution of the differential equations that represent the model---, the prediction is a non-easy task, because the behavioral change of people is reflected in a continuous change of the parameters. A relevant question is what we can use of one city to another; if what happened in Madrid could have been applied to New York and then, if what we have learned from this city would be of use for S\\~ao Paulo. With this idea in mind, we present an analysis of a spreading-rate related measure of COVID-19 as a function of population density and population size for all US counties, as long as for Brazilian cities and German cities. Contrary to what is the common hypothesis in epidemics modeling, we observe a higher {\\em per-capita} contact rate for higher city's population density and population size. Also, we find that the population size has a more explanatory effect than the population density. A contact rate scaling theory is proposed to explain the results.", "qid": 21, "docid": "1ttt1fgr", "rank": 91, "score": 6.551300048828125}, {"content": "Title: COVID-19: intensive care units, mechanical ventilators, and latent mortality profiles associated with case-fatality in Brazil. Content: In response to the accelerated increase in the number of COVID-19 cases, countries must increase their supply of beds in intensive care units (ICUs). Respiratory diseases, neoplasms, cardiopathies and hypertension, and diabetes are associated with higher COVID-19 case-fatality. The study aimed to identify the regions of Brazil with higher specific mortality rates from these comorbidities and the regions with the greatest shortage of ICU beds and mechanical ventilators. A cross-sectional ecological study was performed in which the units of analysis were the country's Health Regions. Data were obtained from Brazilian Health Informatics Department - DATASUS (National Registry of Healthcare Establishments - 2019, Mortality Information Systems - 2017, and Population Projections - 2017). We calculated the disease group-specific mortality rates for hypertension, neoplasms, diabetes, cardiac diseases, respiratory diseases and the rates of total ICU beds, private ICU beds, ICU beds in the Brazilian Unified National Health System (SUS), and ventilators in the SUS, per 100,000 inhabitants. The mortality profile was determined by latent profiles analysis, and the cluster analysis of ICU beds and ventilators used the spatial scan method. Kernel maps were constructed for the data's visualization. Level of significance was set at 5%. Four latent mortality profiles were observed. The Health Regions with the highest mean mortality rates were located in regions with shortages of ICU beds and ventilators, especially in parts of the Northeast, Southeast, and South of Brazil. The spatial localization of regions with both the highest mortality and shortages of ICU beds/ventilators requires attention by policymakers and public planners to deal efficiently and fairly with the COVID-19 epidemic in Brazil.", "qid": 21, "docid": "trwbfefy", "rank": 92, "score": 6.534800052642822}, {"content": "Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "qid": 21, "docid": "uc37poce", "rank": 93, "score": 6.533299922943115}, {"content": "Title: What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study Content: OBJECTIVE: To describe the daily practice of mechanical ventilation (MV), and secondarily, its outcome in pediatric intensive care units (PICUs). DESIGN: Prospective cohort of infants and children who received MV for at least 12 h. SETTING: Thirty-six medical surgical PICUs. PATIENTS: All consecutive patients admitted to the PICUs during 2-month period. MEASUREMENTS AND MAIN RESULTS: Of the 1893 patients admitted, 659 (35%) received MV for a median time of 4 days (25th percentile, 75%: 2, 6). Median of age was 13 months (25th percentile, 75%: 5, 48). Common indications for MV were acute respiratory failure (ARF) in 72% of the patients, altered mental status in 14% of the patients, and ARF on chronic pulmonary disease in 10% of the patients. Median length of stay in the PICUs was 8 days (25th percentile, 75%: 5, 13). Overall mortality rate in the PICUs was 15% (confidence interval 95%: 13\u201318) for the entire population, 50% (95% CI: 25\u201374) in patients who received MV because of acute respiratory distress syndrome, 24% (95% CI: 16\u201335) in patients who received MV for altered mental status and 16% (95% CI: 9\u201329) in patients who received MV for ARF on chronic pulmonary disease. CONCLUSION: One in every 3 patients admitted to the PICUs requires ventilatory support.. The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2225-5", "qid": 21, "docid": "lcbqxeck", "rank": 94, "score": 6.532700061798096}, {"content": "Title: Nonpharmaceutical interventions implemented by US cities during the 1918-1919 influenza pandemic. Content: CONTEXT A critical question in pandemic influenza planning is the role nonpharmaceutical interventions might play in delaying the temporal effects of a pandemic, reducing the overall and peak attack rate, and reducing the number of cumulative deaths. Such measures could potentially provide valuable time for pandemic-strain vaccine and antiviral medication production and distribution. Optimally, appropriate implementation of nonpharmaceutical interventions would decrease the burden on health care services and critical infrastructure. OBJECTIVES To examine the implementation of nonpharmaceutical interventions for epidemic mitigation in 43 cities in the continental United States from September 8, 1918, through February 22, 1919, and to determine whether city-to-city variation in mortality was associated with the timing, duration, and combination of nonpharmaceutical interventions; altered population susceptibility associated with prior pandemic waves; age and sex distribution; and population size and density. DESIGN AND SETTING Historical archival research, and statistical and epidemiological analyses. Nonpharmaceutical interventions were grouped into 3 major categories: school closure; cancellation of public gatherings; and isolation and quarantine. MAIN OUTCOME MEASURES Weekly excess death rate (EDR); time from the activation of nonpharmaceutical interventions to the first peak EDR; the first peak weekly EDR; and cumulative EDR during the entire 24-week study period. RESULTS There were 115,340 excess pneumonia and influenza deaths (EDR, 500/100,000 population) in the 43 cities during the 24 weeks analyzed. Every city adopted at least 1 of the 3 major categories of nonpharmaceutical interventions. School closure and public gathering bans activated concurrently represented the most common combination implemented in 34 cities (79%); this combination had a median duration of 4 weeks (range, 1-10 weeks) and was significantly associated with reductions in weekly EDR. The cities that implemented nonpharmaceutical interventions earlier had greater delays in reaching peak mortality (Spearman r = -0.74, P < .001), lower peak mortality rates (Spearman r = 0.31, P = .02), and lower total mortality (Spearman r = 0.37, P = .008). There was a statistically significant association between increased duration of nonpharmaceutical interventions and a reduced total mortality burden (Spearman r = -0.39, P = .005). CONCLUSIONS These findings demonstrate a strong association between early, sustained, and layered application of nonpharmaceutical interventions and mitigating the consequences of the 1918-1919 influenza pandemic in the United States. In planning for future severe influenza pandemics, nonpharmaceutical interventions should be considered for inclusion as companion measures to developing effective vaccines and medications for prophylaxis and treatment.", "qid": 21, "docid": "b3bphr0j", "rank": 95, "score": 6.531199932098389}, {"content": "Title: Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study Content: Background The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. Methods We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. Results We predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R 0 . The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. Discussion In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.", "qid": 21, "docid": "xtpa84h2", "rank": 96, "score": 6.5254998207092285}, {"content": "Title: Deaths from Covid-19: Who are the forgotten victims? Content: Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.", "qid": 21, "docid": "pn516wom", "rank": 97, "score": 6.501500129699707}, {"content": "Title: Who is going to pay the price of Covid-19? Reflections about an unequal Brazil Content: The COVID-19 pandemic has caused high mortality rates among older people, and in order to avoid a healthcare system crisis, almost all countries worldwide have adopted social isolation measures to prevent the spread of the disease. However, in Brazil, a country demarcated by economic inequalities, in which approximately 25% of the population live below the poverty line, these measures will cost severe economic losses and accentuated starvation. For this reason, the underprivileged population should be immediately prioritized and well informed through good practice to avoid the virus. Since, government discrepancies in dealing with the COVID-19 outbreak leaves the population without congruent guidelines on how to react or what to believe, allowing the spread of fake news and political crises. Here, we discuss who will pay the price of the Brazilian government denying the impact of COVID-19 pandemic and suggest some measures to ensure that clear information and protection reach this population.", "qid": 21, "docid": "fri9zun5", "rank": 98, "score": 6.500899791717529}, {"content": "Title: Central Hepatectomy versus Extended Hepatectomy for Malignant Tumors: A Propensity Score Analysis of Postoperative Complications. Content: BACKGROUND The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 \u00b1 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). METHODS All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. RESULTS The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CONCLUSIONS CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.", "qid": 21, "docid": "aoo3t0iw", "rank": 99, "score": 6.485099792480469}, {"content": "Title: Risk factors associated with mortality after Roux-en-Y gastric bypass surgery. Content: OBJECTIVE We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery. BACKGROUND Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers. METHODS Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed. RESULTS The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P<0.0001), increasing age (P<0.005), male gender (P<0.001), pulmonary hypertension (P<0.0001), congestive heart failure (P=0.0008), and liver disease (P=0.038). When the RYGB risk score was applied, a significant trend (P<0.0001) between increasing risk score and mortality rate is found. CONCLUSIONS Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.", "qid": 21, "docid": "zn3l6lgc", "rank": 100, "score": 6.471499919891357}]}
{"query": "are cardiac complications likely in patients with COVID-19?", "hits": [{"content": "Title: Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19 Content: BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7\u201328% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.", "qid": 22, "docid": "1hvihwkz", "rank": 1, "score": 9.672300338745117}, {"content": "Title: Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19 Content: BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7-28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.", "qid": 22, "docid": "p3fi4yej", "rank": 2, "score": 9.6722993850708}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 22, "docid": "ejsqsn59", "rank": 3, "score": 9.065799713134766}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 22, "docid": "lfjud2aq", "rank": 4, "score": 9.06579875946045}, {"content": "Title: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and Decision tree analysis Content: BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID-19 patients. RESULTS: A meta-analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73-7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84-4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.", "qid": 22, "docid": "0zxj41xe", "rank": 5, "score": 8.765399932861328}, {"content": "Title: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID\u201019 patients: A meta\u2010regression and Decision tree analysis Content: BACKGROUND: Coronavirus disease\u20102019 (COVID\u201019) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID\u201019 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID\u201019 patients. RESULTS: A meta\u2010analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73\u20107.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84\u20104.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID\u201019 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.", "qid": 22, "docid": "g9qlo3xh", "rank": 6, "score": 8.765398979187012}, {"content": "Title: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and decision tree analysis Content: BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.", "qid": 22, "docid": "omplxafd", "rank": 7, "score": 8.765398025512695}, {"content": "Title: Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications Content: The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 22, "docid": "wkp58iov", "rank": 8, "score": 8.583399772644043}, {"content": "Title: Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Content: OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.", "qid": 22, "docid": "hia1me9i", "rank": 9, "score": 8.545900344848633}, {"content": "Title: Spectrum of Neurological Manifestations in Covid-19: A Review. Content: COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache \"personal protection equipment-related headache\" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barr\u00e9 syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barr\u00e9 syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.", "qid": 22, "docid": "qt02t6tf", "rank": 10, "score": 8.515600204467773}, {"content": "Title: Spectrum of Neurological Manifestations in Covid-19: A Review Content: COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache \"personal protection equipment-related headache\" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barr\u00e9 syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barr\u00e9 syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.", "qid": 22, "docid": "tu36aisz", "rank": 11, "score": 8.515599250793457}, {"content": "Title: The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact. Content: SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed.", "qid": 22, "docid": "2cv0p9lb", "rank": 12, "score": 8.482399940490723}, {"content": "Title: The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact Content: SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed.", "qid": 22, "docid": "rkve2z4j", "rank": 13, "score": 8.482398986816406}, {"content": "Title: Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia Content: COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events. The patient described experienced unusually rapid development of pulmonary hypertension (PH) and right ventricular failure after recent severe COVID-19 pneumonia with cytokine release syndrome, which initially was successfully treated with methylprednisolone and tocilizumab. The development of pulmonary hypertension and right ventricular failure \u2013 in the absence of emboli on multiple CT angiograms \u2013 was most likely caused by progressive pulmonary parenchymal abnormalities combined with microvascular damage of the pulmonary arteries (group III and IV pulmonary hypertension, respectively). To the best of our knowledge, these complications have not previously been described and therefore awareness of PH as a complication of COVID-19 is warranted. LEARNING POINTS: COVID-19 increasingly presents with systemic and multi-organ involvement with vascular, thromboembolic and cardiac events. Patients with severe COVID-19 pneumonia and concomitant cytokine release syndrome may be particularly at risk for the development of secondary pulmonary hypertension and right ventricular failure. Pulmonary hypertension can develop unusually rapidly following COVID-19 pneumonia and probably results from progressive pulmonary interstitial and microvascular abnormalities due to COVID-19.", "qid": 22, "docid": "7xqmuoye", "rank": 14, "score": 8.397600173950195}, {"content": "Title: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic Content: Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "qid": 22, "docid": "scddzn5t", "rank": 15, "score": 8.391599655151367}, {"content": "Title: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic Content: ABSTRACT Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "qid": 22, "docid": "ynt2koko", "rank": 16, "score": 8.39159870147705}, {"content": "Title: Coronavirus disease 2019 (COVID-19) and cardiovascular complications Content: Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 22, "docid": "v3qgqfwr", "rank": 17, "score": 8.343899726867676}, {"content": "Title: Cardiac involvement in COVID-19 patients: Risk factors, predictors, and complications: A review Content: BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID-19. RESULTS: Notably, COVID-19 patients with pre-existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID-19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID-19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID-19 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "qid": 22, "docid": "0ec1cu8q", "rank": 18, "score": 8.312999725341797}, {"content": "Title: Cardiac involvement in COVID\u201019 patients: Risk factors, predictors, and complications: A review Content: BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS\u2010CoV\u20102/COVID\u201019), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID\u201019. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID\u201019. RESULTS: Notably, COVID\u201019 patients with pre\u2010existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID\u201019, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID\u201019 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID\u201019 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "qid": 22, "docid": "qsy2kex1", "rank": 19, "score": 8.31299877166748}, {"content": "Title: SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know Content: There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "qid": 22, "docid": "2k1n07on", "rank": 20, "score": 8.277799606323242}, {"content": "Title: SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know. Content: There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "qid": 22, "docid": "8ysfaww2", "rank": 21, "score": 8.277798652648926}, {"content": "Title: Acute Myocardial Injury of Patients with Coronavirus Disease 2019 Content: Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.", "qid": 22, "docid": "jg6v644y", "rank": 22, "score": 8.223199844360352}, {"content": "Title: Management of COVID-19 in people with epilepsy: drug considerations Content: People with epilepsy (PWE) are neither more likely to be infected by the coronavirus nor are they more likely to have severe COVID-19 manifestations because they suffer from epilepsy. However, management of COVID-19 in PWE may be more complicated than that in other individuals. Drug-drug interactions could pose significant challenges and cardiac, hepatic, or renal problems, which may happen in patients with severe COVID-19, may require adjustment to antiepileptic drugs (AEDs). In this review, we first summarize the potential drug-drug interactions between AEDs and drugs currently used in the management of COVID-19. We then summarize other challenging issues that may happen in PWE, who have COVID-19 and are receiving treatment.", "qid": 22, "docid": "x9t3o95c", "rank": 23, "score": 8.07699966430664}, {"content": "Title: Cardiac and arrhythmic complications in patients with COVID-19 Content: In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Although coronavirus disease (COVID-19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2-receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID-19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID-19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID-19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS-CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "qid": 22, "docid": "rmio55bx", "rank": 24, "score": 8.058899879455566}, {"content": "Title: Cardiac and arrhythmic complications in patients with COVID\u201019 Content: In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102). Although coronavirus disease (COVID\u201019) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2\u2010receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID\u201019 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID\u201019 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID\u201019 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS\u2010CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "qid": 22, "docid": "xhum1ykr", "rank": 25, "score": 8.05889892578125}, {"content": "Title: One train may hide another: Acute cardiovascular diseases could be neglected because of the COVID-19 pandemic Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is likely to have significant implications for the cardiovascular care of patients. In most countries, containment has already started (on 17 March 2020 in France), and self-quarantine and social distancing are reducing viral contamination and saving lives. However, these considerations may only be the tip of the iceberg; most resources are dedicated to the struggle against COVID-19, and this unprecedented situation may compromise the management of patients admitted with cardiovascular conditions. AIM: We aimed to assess the effect of COVID-19 containment measures on cardiovascular admissions in France. METHODS: We asked nine major cardiology centres to give us an overview of admissions to their nine intensive cardiac care units for acute myocardial infarction or acute heart failure, before and after containment measures. RESULTS: Before containment (02-16 March 2020), the nine participating intensive cardiac care units admitted 4.8\u00b11.6 patients per day, versus 2.6\u00b11.5 after containment (17-22 March 2020) (rank-sum test P=0.0006). CONCLUSIONS: We confirm here, for the first time, a dramatic drop in the number of cardiovascular admissions after the establishment of containment. Many hypotheses might explain this phenomenon, but we feel it is time raise the alarm about the risk for patients presenting with acute cardiovascular disease, who may suffer from lack of attention, leading to severe consequences (an increase in the number of ambulatory myocardial infarctions, mechanical complications of myocardial infarction leading to an increase in the number of cardiac arrests, unexplained deaths, heart failure, etc.). Similar consequences can be feared for all acute situations, beyond the cardiovascular disease setting.", "qid": 22, "docid": "0yuq7vym", "rank": 26, "score": 7.995100021362305}, {"content": "Title: One train may hide another: Acute cardiovascular diseases could be neglected because of the COVID-19 pandemic Content: Summary Background Coronavirus disease 2019 (COVID-19) is likely to have significant implications for the cardiovascular care of patients. In most countries, containment has already started (on 17 March 2020 in France), and self-quarantine and social distancing are reducing viral contamination and saving lives. However, these considerations may only be the tip of the iceberg; most resources are dedicated to the struggle against COVID-19, and this unprecedented situation may compromise the management of patients admitted with cardiovascular conditions. Aim We aimed to assess the effect of COVID-19 containment measures on cardiovascular admissions in France. Methods We asked nine major cardiology centres to give us an overview of admissions to their nine intensive cardiac care units for acute myocardial infarction or acute heart failure, before and after containment measures. Results Before containment (02\u201316 March 2020), the nine participating intensive cardiac care units admitted 4.8\u00b11.6 patients per day, versus 2.6\u00b11.5 after containment (17\u201322 March 2020) (rank-sum test P =0.0006). Conclusions We confirm here, for the first time, a dramatic drop in the number of cardiovascular admissions after the establishment of containment. Many hypotheses might explain this phenomenon, but we feel it is time raise the alarm about the risk for patients presenting with acute cardiovascular disease, who may suffer from lack of attention, leading to severe consequences (an increase in the number of ambulatory myocardial infarctions, mechanical complications of myocardial infarction leading to an increase in the number of cardiac arrests, unexplained deaths, heart failure, etc.). Similar consequences can be feared for all acute situations, beyond the cardiovascular disease setting.", "qid": 22, "docid": "2nlnyxct", "rank": 27, "score": 7.995099067687988}, {"content": "Title: Cardiac sequelae of novel coronavirus disease 2019 (COVID-19): a clinical case series Content: BACKGROUND: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 most commonly manifests with fever and respiratory illness. The cardiovascular manifestations have become more prevalent but can potentially go unrecognized. We look to describe cardiac manifestations in three patients with COVID-19 using cardiac enzymes, electrocardiograms, and echocardiography. CASE SUMMARIES: The first patient, a 67-year-old Caucasian female with non-ischaemic dilated cardiomyopathy, presented with dyspnoea on exertion and orthopnoea 1 week after testing positive for COVID-19. Echocardiogram revealed large pericardial effusion with findings consistent with tamponade. A pericardial drain was placed, and fluid studies were consistent with viral pericarditis, treated with colchicine, hydroxychloroquine, and methylprednisolone. Follow-up echocardiograms showed apical hypokinesis, that later resolved, consistent with Takotsubo syndrome. The second patient, a 46-year-old African American male with obesity and type 2 diabetes mellitus presented with fevers, cough, and dyspnoea due to COVID-19. Clinical course was complicated with pulseless electrical activity arrest; he was found to have D-dimer and troponin elevation, and inferior wall ST elevation on ECG concerning for STEMI due to microemboli. The patient succumbed to the illness. The third patient, a 76-year-old African American female with hypertension, presented with diarrhoea, fever, and myalgia, and was found to be COVID-19 positive. Clinical course was complicated, with acute troponin elevation, decreased cardiac index, and severe hypokinesis of the basilar wall suggestive of reverse Takotsubo syndrome. The cardiac index improved after pronation and non-STEMI therapy; however, the patient expired due to worsening respiratory status. DISCUSSION: These case reports demonstrate cardiovascular manifestations of COVID-19 that required monitoring and urgent intervention.", "qid": 22, "docid": "x629iv3f", "rank": 28, "score": 7.942399978637695}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management Content: As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.", "qid": 22, "docid": "q82gkygd", "rank": 29, "score": 7.8668999671936035}, {"content": "Title: First case of COVID-19 complicated with fulminant myocarditis: a case report and insights Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.", "qid": 22, "docid": "4dnuilqg", "rank": 30, "score": 7.859399795532227}, {"content": "Title: The role of cardiac imaging in hospitalized COVID-19-positive patients Content: COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.", "qid": 22, "docid": "ozy39172", "rank": 31, "score": 7.834400177001953}, {"content": "Title: The role of cardiac imaging in hospitalized COVID-19-positive patients. Content: COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.", "qid": 22, "docid": "q5p0ie3j", "rank": 32, "score": 7.834399223327637}, {"content": "Title: Neurological manifestations and complications of COVID-19: A Literature Review Content: Abstract The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2109 and rapidly spread to more than 200 countries as a global health pandemic. There are more than 2.3 million confirmed cases and around 165,000 fatalities. The primary manifestation is respiratory and cardiac but neurological features are also being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.", "qid": 22, "docid": "gjctfjub", "rank": 33, "score": 7.820300102233887}, {"content": "Title: Neurological manifestations and complications of COVID-19: A literature review Content: The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread to more than 200 countries as a global health pandemic. There are more than 3.5 million confirmed cases and around 165,000 to 243,000 fatalities. The primary manifestation is respiratory and cardiac but neurological features are also being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.", "qid": 22, "docid": "lo705hfr", "rank": 34, "score": 7.82029914855957}, {"content": "Title: Emerging cardiological issues during the COVID\u201019 pandemic Content: Today the modern world is facing an unprecedented health crisis. The COVID\u201019 pandemic is putting extensive strain on health care systems, hospitals and medical workers worldwide. Epidemiological data are emerging that COVID\u201019 patients with cardiac risk factors or pre\u2010existing cardiac conditions are at increased risk for complications and mortality from COVID\u201019. As we just begin to understand the pathophysiology underlying the disease, the involvement of the heart, whether through direct myocardial infection and damage or due to cardiac complications, is already evident.", "qid": 22, "docid": "6p39cx2e", "rank": 35, "score": 7.811999797821045}, {"content": "Title: Cardiac manifestations in COVID-19 patients-A systematic review. Content: OBJECTIVES The coronavirus disease-2019 (COVID-19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases. The association between COVID-19 and the cardiovascular system has been well described. We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac-specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity. METHODS A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID-19 patients, and cardiac-specific biomarkers with their clinical implications on COVID-19. RESULTS Sixty-one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP). Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID-19 and thus help to save lives. A wide array of cardiac manifestations is associated with the interaction between COVID-19 and the cardiovascular system. Cardiac-specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion. CONCLUSION COVID-19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.", "qid": 22, "docid": "8otl3781", "rank": 36, "score": 7.809800148010254}, {"content": "Title: Cardiac manifestations in COVID-19 patients-A systematic review Content: OBJECTIVES: The coronavirus disease-2019 (COVID-19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases. The association between COVID-19 and the cardiovascular system has been well described. We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac-specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity. METHODS: A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID-19 patients, and cardiac-specific biomarkers with their clinical implications on COVID-19. RESULTS: Sixty-one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP). Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID-19 and thus help to save lives. A wide array of cardiac manifestations is associated with the interaction between COVID-19 and the cardiovascular system. Cardiac-specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion. CONCLUSION: COVID-19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.", "qid": 22, "docid": "qbby61wj", "rank": 37, "score": 7.8097991943359375}, {"content": "Title: Acute Life-threatening Cardiac Tamponade in a Mechanically Ventilated Patient with COVID-19 Pneumonia Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently evolved as a pandemic disease. Although the respiratory system is predominantly affected, cardiovascular complications have been frequently identified, including acute myocarditis, myocardial infarction, acute heart failure, arrhythmias and venous thromboembolic events. Pericardial disease has been rarely reported. We present a case of acute life-threatening cardiac tamponade caused by a small pericardial effusion in a mechanically ventilated patient with severe COVID-19 associated pneumonia. The patient presented acute circulatory collapse with hemodynamic features of cardiogenic or obstructive shock. Bedside echocardiography permitted prompt diagnosis and life-saving pericardiocentesis. Further investigation revealed no other apparent cause of pericardial effusion except for SARS-CoV-2 infection. Cardiac tamponade may complicate COVID-19 and should be included in the differential diagnosis of acute hemodynamic deterioration in mechanically ventilated COVID-19 patients.", "qid": 22, "docid": "p7iraa2k", "rank": 38, "score": 7.798399925231934}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of \u226411mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of \u22651.5 \u03bcg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of \u226510 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \ufeffmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 22, "docid": "5m4ybd1v", "rank": 39, "score": 7.7829999923706055}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of &#8804;11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of &#8805;1.5 \u00b5g/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of &#8805;10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \u00ef\u00bb\u00bfmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 22, "docid": "nmolo7rt", "rank": 40, "score": 7.782999038696289}, {"content": "Title: Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19) Content: Importance: Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant: This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure: Cardiac involvement with COVID-19. Main Outcomes and Measures: Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results: An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance: This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.", "qid": 22, "docid": "m5ji2gu4", "rank": 41, "score": 7.735000133514404}, {"content": "Title: Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). Content: Importance Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure Cardiac involvement with COVID-19. Main Outcomes and Measures Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.", "qid": 22, "docid": "ysyqai97", "rank": 42, "score": 7.734999179840088}, {"content": "Title: Acute Pericarditis and Cardiac Tamponade in a Patient with COVID-19: A Therapeutic Challenge Content: We report a case of acute viral pericarditis and cardiac tamponade in a patient with COVID-19 to highlight the associated treatment challenges, especially given the uncertainty associated with the safety of standard treatment. We also discuss complications associated with delayed diagnosis in patients who potentially may need mechanical ventilation. LEARNING POINTS: Large pericardial effusion and cardiac tamponade should be considered in patients with COVID-19 who decompensate further after intubation and mechanical ventilation. The characteristics of pericardial effusion in patients with COVID-19 are described. A successful treatment approach for acute pericarditis in a patient with COVID-19 in light of differing opinions over the safety of NSAID use is described.", "qid": 22, "docid": "cal5fi30", "rank": 43, "score": 7.683899879455566}, {"content": "Title: Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients. Content: Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.", "qid": 22, "docid": "95wclabe", "rank": 44, "score": 7.654300212860107}, {"content": "Title: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart Content: Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.", "qid": 22, "docid": "0376d6vf", "rank": 45, "score": 7.642600059509277}, {"content": "Title: Impact of Congestive Heart Failure and Role of Cardiac Biomarkers in COVID-19 patients: A Systematic Review and Meta-Analysis Content: Background: Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. Methods: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies were used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. Results: We collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p<0.001); and 3.61 (95% CI 2.03-6.43) (p=0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p=0.022) and 1.52 (95% CI 1.12-2.05) (p=0.008) among patients who had pre-existing CHF and hypertension, respectively. Conclusion: Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes. Keywords: Acute cardiac injury; cardiac arrhythmia; mortality risk; cardiac biomarkers, COVID-19.", "qid": 22, "docid": "xapokjgd", "rank": 46, "score": 7.641200065612793}, {"content": "Title: Approach to Acute Cardiovascular Complications in COVID-19 Infection Content: The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a \"Heart-Lung\" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "qid": 22, "docid": "gs45hgch", "rank": 47, "score": 7.621099948883057}, {"content": "Title: Approach to Acute Cardiovascular Complications in COVID-19 Infection. Content: The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a \"Heart-Lung\" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "qid": 22, "docid": "mol4s3iz", "rank": 48, "score": 7.62109899520874}, {"content": "Title: Approach to Acute Cardiovascular Complications in COVID-19 Infection Content: The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "qid": 22, "docid": "sw0xtwno", "rank": 49, "score": 7.621098041534424}, {"content": "Title: Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City Content: Importance: Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined. From March 1 to April 25, 2020, New York City, New York (NYC), reported 17\u00e2\u0080\u00af118 COVID-19-related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year. Objective: To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC. Design, Setting, and Participants: This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019. The NYC 911 EMS system serves more than 8.4 million people. Exposures: The COVID-19 pandemic. Main Outcomes and Measures: Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests. Results: A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period. The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100\u00e2\u0080\u00af000 vs 15.9/100\u00e2\u0080\u00af000). Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]). Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001). Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%. These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001]). Conclusions and Relevance: In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms. Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.", "qid": 22, "docid": "6x8h03u8", "rank": 50, "score": 7.593599796295166}, {"content": "Title: Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City Content: IMPORTANCE: Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined. From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19\u2013related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year. OBJECTIVE: To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019. The NYC 911 EMS system serves more than 8.4 million people. EXPOSURES: The COVID-19 pandemic. MAIN OUTCOMES AND MEASURES: Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests. RESULTS: A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period. The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100 000 vs 15.9/100 000). Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]). Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001). Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%. These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001]). CONCLUSIONS AND RELEVANCE: In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms. Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.", "qid": 22, "docid": "kxx3szjq", "rank": 51, "score": 7.59359884262085}, {"content": "Title: Critical Complications of COVID-19: A systematic Review and Meta-Analysis study Content: Background: Coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has spread worldwide in a short period and caused a pandemic. The goal of this meta-analysis is to evaluate the prevalence of most common symptoms and complications of COVID-19. Methods: All related studies assessing the clinical complications of COVID-19 have been identified through web search databases (PubMed and Scopus). Relevant data were extracted from these studies and analyzed by stata (ver 14) random-effects model. The heterogeneity of studies were assessed by I2 index. The publication bias was examined by Funnel plots and Eggers test. Results: 30 studies were in our meta-analysis including 6 389 infected patients. The prevalence of most common symptoms were: fever 84.30% (95% CI: 77.13-90.37; I2=97.74%), cough 63.01% (95% CI: 57.63-68.23; I2=93.73%), dyspnea 37.16% (95% CI: 27.31-47.57%; I2=98.32%), fatigue 34.22% (95% CI: 26.29-42.62; I2=97.29%) and diarrhea 11.47 %(95% CI: 6.96-16.87; I2=95.58%), respectively. The most prevalent complications were acute respiratory distress syndrome (ARDS) 33.15% (95% CI: 23.35-43.73; I2=98.56%), acute cardiac injury 13.77% (95% CI: 9.66-18.45; I2=91.36%), arrhythmia 16.64% (95% CI: 9.34-25.5; I2=92.29%), heart failure 11.50% (95% CI: 3.45-22.83; I2=89.48%), and acute kidney injury (AKI) 8.40 %(95% CI: 5.15-12.31; I2=95.22%, respectively. According to our analysis, mortality rate of COVID-19 patients were 12.29% (95% CI: 6.20-19.99; I2=98.29%). Conclusion: We assessed the prevalence of the main clinical complications of COVID-19 and found that after respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.", "qid": 22, "docid": "aks5z29t", "rank": 52, "score": 7.554900169372559}, {"content": "Title: Indian resuscitation council (IRC) suggested guidelines for comprehensive cardiopulmonary life support (CCLS) for suspected or confirmed coronavirus disease (COVID-19) patient Content: Management of the recent outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) remains challenging. The challenges are not only limited to its preventive strategies, but also extend to curative treatment, and are amplified during the management of critically ill patients with COVID-19. Older persons with comorbidities like diabetes mellitus, cardiac diseases, hepatic impairment, renal disorders and respiratory pathologies or immune impairing conditions are more vulnerable and have a higher mortality from COVID-19. Earlier, the Indian Resuscitation Council (IRC) had proposed the Comprehensive Cardiopulmonary Life Support (CCLS) for management of cardiac arrest victims in the hospital setting. However, in patients with COVID-19, the guidelines need to be modified,due to various concerns like differing etiology of cardiac arrest, virulence of the virus, risk of its transmission to rescuers, and the need to avoid or minimize aerosolization from the patient due to various interventions. There is limited evidence in these patients, as the SARS-CoV-2 is a novel infection and not much literature is available with high-level evidence related to CPR in patients of COVID-19. These suggested guidelines are a continuum of CCLS guidelines by IRC with an emphasis on the various challenges and concerns being faced during the resuscitative management of COVID-19 patients with cardiopulmonary arrest.", "qid": 22, "docid": "0j3qaxg0", "rank": 53, "score": 7.535600185394287}, {"content": "Title: The Use of Decision Modelling to Inform Timely Policy Decisions on Cardiac Resource Capacity During the COVID-19 Pandemic Content: In Ontario on March 16, 2020, a directive was issued to all acute care hospitals to halt nonessential procedures in anticipation of a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for 3 key groups of cardiovascular disease patients: coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across 5 regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.", "qid": 22, "docid": "166ds3tl", "rank": 54, "score": 7.528299808502197}, {"content": "Title: The Use of Decision Modelling to Inform Timely Policy Decisions on Cardiac Resource Capacity during the COVID-19 Pandemic Content: In Ontario, on March 16th, 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for three key groups of cardiovascular disease patients; coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across five regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely, data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.", "qid": 22, "docid": "953hxgs6", "rank": 55, "score": 7.528298854827881}, {"content": "Title: The Use of Decision Modelling to Inform Timely Policy Decisions on Cardiac Resource Capacity during the COVID-19 Pandemic. Content: In Ontario, on March 16(th), 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for three key groups of cardiovascular disease patients; coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across five regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely, data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.", "qid": 22, "docid": "jlinwjp4", "rank": 56, "score": 7.5282979011535645}, {"content": "Title: The cardiac intensive care unit and the cardiac Intensivist during the COVID-19 surge in New York City() Content: Critical care cardiology has been impacted by the coronavirus disease-2019 (COVID-19) pandemic. COVID-19 causes severe acute respiratory distress syndrome, acute kidney injury, as well as several cardiovascular complications including myocarditis, venous thromboembolic disease, cardiogenic shock, and cardiac arrest. The cardiac intensive care unit is rapidly evolving as the need for critical care beds increases. Herein, we describe the changes to the cardiac intensive care unit and the evolving role of critical care cardiologists and other clinicians in the care of these complex patients affected by the COVID-19 pandemic. These include practical recommendations regarding a structural and organizational changes to facilitate care of patients with COVID-19; staffing and personnel changes; and health and safety of personnel. We draw upon our own experiences at NewYork-Presbyterian Columbia University Irving Medical Center to offer insights into the unique challenges facing critical care clinicians and provide recommendations of how to address these challenges during this unprecedented time.", "qid": 22, "docid": "ei768v4s", "rank": 57, "score": 7.519999980926514}, {"content": "Title: Myocardial injury and COVID-19: Possible mechanisms Content: Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.", "qid": 22, "docid": "smkpp89u", "rank": 58, "score": 7.485400199890137}, {"content": "Title: Myocardial injury and COVID-19: Possible mechanisms Content: Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.", "qid": 22, "docid": "ter67nri", "rank": 59, "score": 7.48539924621582}, {"content": "Title: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response Content: PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "qid": 22, "docid": "6f8la6sw", "rank": 60, "score": 7.476500034332275}, {"content": "Title: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response Content: PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "qid": 22, "docid": "xkg0ylz8", "rank": 61, "score": 7.476499080657959}, {"content": "Title: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients Content: Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. Design: Systematic review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study Selection: Published and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome Measures: The outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: 49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). Conclusion: Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review Registration: PROSPERO 2020: CRD42020186527.", "qid": 22, "docid": "9hdft1tc", "rank": 62, "score": 7.47599983215332}, {"content": "Title: SARS-CoV-2 (COVID-19) and intravascular volume management strategies in the critically ill Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread across the globe, and millions of people may be affected. While knowledge regarding epidemiologic features and diagnostic tools of coronavirus disease 2019 (COVID-19) is rapidly evolving, uncertainties surrounding various aspects of its optimal management strategies persist. A subset of these patients develop a more severe form of the disease characterized by expanding pulmonary lesions, sepsis, acute respiratory distress syndrome, and respiratory failure. Due to lack of data on treatment strategies specific to this subset of patients, currently available evidence on management of the critically ill needs to be extrapolated and customized to their clinical needs. The article calls attention to fluid stewardship in the critically ill with COVID-19 by judiciously applying the evidence-based resuscitation principles to their specific clinical features such as high rates of cardiac injury. As we await more data from treating these patients, this strategy is likely to help reduce potential complications.", "qid": 22, "docid": "5yan9fcn", "rank": 63, "score": 7.452199935913086}, {"content": "Title: A Review of Cardiac Complications in Coronavirus Disease 2019 Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has shown an association with acute myocardial injury, cardiomyopathy, and myocarditis. Individuals with myocardial involvement in association with the coronavirus disease 2019 (COVID-19) may be at increased risk of developing severe illness. Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. It has been primarily divided into three subsets: genetic, mixed, and acquired cardiomyopathy. We anticipate that, because of the high inflammatory response, other cardiovascular complications may also occur in COVID-19 patients with severe symptoms. This review explores new information as it pertains to COVID-19 and cardiac complications.", "qid": 22, "docid": "u6vq5ohr", "rank": 64, "score": 7.449699878692627}, {"content": "Title: COVID-19 and Cardiac Arrhythmias Content: BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVE: To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50\u00b118 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 - 13.18]) and NSVT (OR 8.92 [95% CI 1.73 - 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 - 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 - 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.", "qid": 22, "docid": "0yq5ror7", "rank": 65, "score": 7.447299957275391}, {"content": "Title: COVID-19 and Cardiac Arrhythmias Content: BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVE: To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50\u00b118 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 \u2013 13.18]) and NSVT (OR 8.92 [95% CI 1.73 \u2013 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 \u2013 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 \u2013 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.", "qid": 22, "docid": "sejk04z7", "rank": 66, "score": 7.447299003601074}, {"content": "Title: Determinants of cardiac adverse events of chloroquine and hydroxychloroquine in 20 years of drug safety surveillance reports Content: Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to the risk of drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.", "qid": 22, "docid": "mjdg84ny", "rank": 67, "score": 7.429599761962891}, {"content": "Title: What should a cardiologist know about coronavirus disease 2019? Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2011CoV\u20112) is the cause of coronavirus disease 2019 (COVID\u201119). The most common symptoms of COVID\u201119 are: fever (81.8%-100%), cough (46.3%-86.2%), myalgia and fatigue (11%-50%), expectoration (4.4%-72%), and dyspnea (18.6%-59%). The most common laboratory abnormalities in COVID\u201119 include decreased lymphocyte count (35%-82.1%), thrombocytopenia (17%-36.2%), elevated serum C\u2011reactive protein (60.7%-93%), lactate dehydrogenase (41%-76%), and D\u2011dimer concentrations (36%-46.4%). Among comorbidities in patients with COVID\u201119, cardiovascular disease is most commonly found. In addition, patients with concomitant cardiovascular diseases have worse prognosis and more often require admission to the intensive care unit (ICU), compared with patients without such comorbidities. It is estimated that about 20% of patients with COVID\u201119 develop cardiac injury. Cardiac injury is more prevalent among patients with COVID\u201119 who require ICU care. In a group of critically ill patients, 27.5% had an elevated N\u2011terminal pro-B\u2011type natriuretic peptide concentration, and increased cardiac troponin level was found in 10% of patients. One of the life\u2011threatening cardiac manifestations is coronavirus fulminant myocarditis, which may also occur without accompanying symptoms of pulmonary involvement. Early recognition and treatment is crucial in these cases. So far, data on the incidence of arrhythmias in patients with COVID\u201119 are limited. Coronavirus disease 2019 impacts patients with cardiovascular comorbidities and affects daily practice of cardiologists. Thus, it is important to know typical COVID\u201119 symptoms, possible clinical manifestations, complications, and recommended treatment.", "qid": 22, "docid": "3v64a4ei", "rank": 68, "score": 7.416100025177002}, {"content": "Title: Potential mechanisms of cardiac injury and common pathways of inflammation in patients with COVID-19 Content: Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with COVID-19 still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel SARS-CoV2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.", "qid": 22, "docid": "cuv5xxoj", "rank": 69, "score": 7.414700031280518}, {"content": "Title: Arterial thromboembolic complications in COVID\u201019 in low\u2010risk patients despite prophylaxis Content: We present a case series of three patients with COVID-19 who developed arterial vascular complications, one who developed an acute CVA, one who developed popliteal artery occlusion and one who developed both during their hospital course. We present a case series of three patients admitted to Northwell Plainview Hospital in Plainview, New York with COVID-19 as confirmed by PCR. The clinical disease course of COVID-19 has been well documented in China and Europe and most recently, the United States. Publications highlighting the non-respiratory complications of COVID-19 have been limited.[1, 2] Acute cardiac injury and arrhythmia in the ICU have been described as major complications of COVID-19.[3] A few publications have highlighted the incidence of venous thromboembolic complications in COVID-19.[4, 5].", "qid": 22, "docid": "01yzk0au", "rank": 70, "score": 7.4045000076293945}, {"content": "Title: Potential Mechanisms of Cardiac Injury and Common Pathways of Inflammation in Patients With COVID-19 Content: Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.", "qid": 22, "docid": "rhvv3l0l", "rank": 71, "score": 7.338500022888184}, {"content": "Title: A current review of COVID-19 for the cardiovascular specialist Content: Abstract Although Coronavirus Disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include 1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; 2) acute coronary syndrome due to acute atherothrombosis in a virally-induced thrombotic and inflammatory milieu; 3) microvascular dysfunction due to diffuse microthrombi or vascular injury; 4) stress-related cardiomyopathy (Takotsubo syndrome); 5) non-ischemic myocardial injury due to a hyperinflammatory cytokine storm; or 6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, d-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative non-ischemic causes of injury, integrating the level of suspicion for COVID-19.", "qid": 22, "docid": "dm9nefdg", "rank": 72, "score": 7.327199935913086}, {"content": "Title: A current review of COVID-19 for the cardiovascular specialist Content: Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.", "qid": 22, "docid": "umhj7nk7", "rank": 73, "score": 7.3271989822387695}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 22, "docid": "5gd0q8yq", "rank": 74, "score": 7.324699878692627}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care. Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 22, "docid": "nj0ue2c2", "rank": 75, "score": 7.3246989250183105}, {"content": "Title: Acute Necrotizing Encephalitis in Viral Respiratory Tract Infection: An Autopsy Case Report Content: Acute necrotizing encephalitis (ANE) is a rare complication of viral respiratory tract infections, with specific histological changes. The condition is most commonly described in the pediatric population, however, it can also develop in the elderly, with some genetic factors being described as contributory. Herein, we report the autopsy finding of a patient with a viral respiratory tract infection, complicated with ANE. The patient was a 77-year-old female with multiple comorbidities living in a social home. For the two months prior, she had been hospitalized with cerebral infarction, respiratory tract infection, and exacerbation of chronic cardiac failure and concomitant hypertension and type 2 diabetes. On gross examination, the brain was edematous, with ground-glass opacity meninges a focus of encephalomalacia in the right cerebral hemisphere and multiple petechial hemorrhages. Histology revealed diffuse foci of encephalitis, with large areas of neuronal necrosis (coagulative-like necrosis) around the blood vessels and a sharp border with the surrounding healthy parenchyma - ANE. The patients tested negative for coronavirus disease 2019 (COVID-19).", "qid": 22, "docid": "98zjtbx6", "rank": 76, "score": 7.307799816131592}, {"content": "Title: A nationwide survey of UK cardiac surgeons' view on clinical decision making during the coronavirus disease 2019 (COVID-19) pandemic Content: BACKGROUND: No firm recommendations are currently available to guide decision making for patients requiring cardiac surgery during the coronavirus disease 2019 (COVID-19) pandemic. Systematic appraisal of senior surgeons' consensus can be used to generate interim recommendations until data from clinical observations become available. Hence, we aimed to collect and quantitatively appraise nationwide UK consultants' opinions on clinical decision making for patients requiring cardiac surgery during the COVID-19 pandemic. METHODS: We E-mailed a Web-based questionnaire to all consultant cardiac surgeons through the Society for Cardiothoracic Surgery in Great Britain and Ireland mailing list on the April 17, 2020, and we predetermined to close the survey on the April 21, 2020. This survey was primarily designed to gather information on UK surgeons' opinions using 12 items. Strong consensus was predefined as an opinion shared by at least 60% of responding consultants. RESULTS: A total of 86 consultant surgeons undertook the survey. All UK cardiac units were represented by at least 1 consultant. Strong consensus was achieved for the following key questions: (1) before any hospital admission for cardiac surgery, nasopharyngeal swab, polymerase chain reaction, and computed tomography of the chest should be performed; (2) the use of full personal protective equipment should to be adopted in every case by the theater team regardless of the patient's COVID-19 status; (3) the risk of COVID-19 exposure for patients undergoing heart surgery should be considered moderate to high and likely to increase mortality if it occurs; and (4) cardiac procedures should be decided based on a rapidly convened multidisciplinary team discussion for every patient. The majority believed that both aortic and mitral surgery should be considered in selected cases. The role of coronary artery bypass graft surgery during the pandemic was controversial. CONCLUSIONS: In this unprecedented pandemic period, this survey provides information for generating interim recommendations until data from clinical observations become available.", "qid": 22, "docid": "2h81uqvu", "rank": 77, "score": 7.2469000816345215}, {"content": "Title: A Nationwide Survey of UK cardiac surgeons\u2019 view on clinical decision making during the COVID-19 pandemic Content: Abstract Background No firm recommendations are currently available to guide decision making for patients requiring cardiac surgery during the COVID-19 pandemic. Systematic appraisal of senior surgeons\u2019 consensus can be used to generate interim recommendations until data from clinical observations will become available. Hence, we aimed to collect and quantitatively appraise nationwide UK consultants\u2019 opinion on clinical decision making for patients requiring cardiac surgery during the COVID-19 pandemic. Methods We mailed a web-based questionnaire to all consultant cardiac surgeons through the Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS) mailing list on the 17th April 2020 and we pre-determined to close the survey on the 21st April 2020. This survey was primarily designed to gather information on UK surgeons\u2019 opinion using 12 items. Strong consensus was predefined as an opinion shared by at least 60% of responding consultants. Results A total of 86 consultant surgeons undertook the survey. All UK cardiac units were represented by at least one consultant. Strong consensus was achieved for the following key questions:1) before any hospital admission for cardiac surgery, nasopharyngeal swab, r-PCR and chest CT should be performed; 2) the use of full PPE should to be adopted in every case by the theatre team regardless patient\u2019s COVID-19 status; 3) the risk of COVID-19 exposure for patients undergoing heart surgery should be considered moderate to high and likely to increase mortality if it occurs; 4) cardiac procedure should be decided based on a rapidly convened multidisciplinary team discussion for every patient. The majority believed that both aortic and mitral surgery should be considered in selected cases. The role of coronary artery bypass graft surgery during the pandemic was controversial. Conclusions In this unprecedented pandemic period, this survey provides information for generating interim recommendations until data from clinical observations will become available.", "qid": 22, "docid": "tsg86qav", "rank": 78, "score": 7.246899127960205}, {"content": "Title: A Case of Postoperative Covid-19 Infection After Cardiac Surgery: Lessons Learned Content: While the focus of the medical community is on the management of COVID-19 and its associated complex presentations, it is critical to recognize that patients will continue to present with other medical problems that require urgent therapeutic interventions. There is growing concern that such interventions might have an impact on the natural history of COVID-19. We present a case of a patient who presented with unstable angina and multivessel coronary artery disease for which coronary artery bypass surgery was indicated and performed. Unfortunately, he succumbed to respiratory complications attributed to COVID-19. Our experience suggests concern about adverse outcomes in patients undergoing cardiac surgery who might be infected with COVID-19. Clearly, additional investigations and experience are needed.", "qid": 22, "docid": "euvj2vvm", "rank": 79, "score": 7.23829984664917}, {"content": "Title: A Case of Postoperative Covid-19 Infection After Cardiac Surgery: Lessons Learned. Content: While the focus of the medical community is on the management of COVID-19 and its associated complex presentations, it is critical to recognize that patients will continue to present with other medical problems that require urgent therapeutic interventions. There is growing concern that such interventions might have an impact on the natural history of COVID-19. We present a case of a patient who presented with unstable angina and multivessel coronary artery disease for which coronary artery bypass surgery was indicated and performed. Unfortunately, he succumbed to respiratory complications attributed to COVID-19. Our experience suggests concern about adverse outcomes in patients undergoing cardiac surgery who might be infected with COVID-19. Clearly, additional investigations and experience are needed.", "qid": 22, "docid": "ynr758pj", "rank": 80, "score": 7.2382988929748535}, {"content": "Title: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. Content: Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/\u03bcL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] \u03bcg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] \u03bcg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.", "qid": 22, "docid": "qxqo23i9", "rank": 81, "score": 7.232699871063232}, {"content": "Title: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Content: Importance: Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective: To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants: This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures: Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results: A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13\u00e2\u0080\u00af800] vs 5500 [4200-7400] cells/\u00b5L) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] \u00b5g/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] \u00b5g/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance: Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.", "qid": 22, "docid": "rzvws6op", "rank": 82, "score": 7.232698917388916}, {"content": "Title: Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series Content: OBJECTIVE: A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19. CASES: COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO2. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers. RESULTS: All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition. CONCLUSION: This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.", "qid": 22, "docid": "ayqigfmr", "rank": 83, "score": 7.232500076293945}, {"content": "Title: Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series. Content: OBJECTIVE A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19. CASES COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO2. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers. RESULTS All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition. CONCLUSION This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.", "qid": 22, "docid": "k61vabjh", "rank": 84, "score": 7.232499122619629}, {"content": "Title: Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.", "qid": 22, "docid": "ye15hb3y", "rank": 85, "score": 7.231900215148926}, {"content": "Title: Coronavirus Disease and New-Onset Atrial Fibrillation: Two Cases Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a considerable amount of morbidity and mortality worldwide since December 2019. Patients with coronavirus disease (COVID-19) most commonly present with respiratory manifestations, while cardiac manifestations were reported as a complication and seldom as a presenting feature. We report two cases of new-onset atrial fibrillation occurring in middle-aged men with no significant past medical history. The first patient presented with symptomatic atrial fibrillation; however, during his hospitalization course, he developed a fever, which led to the diagnosis of infection with SARS-CoV-2. The second patient presented from urgent care after being diagnosed with COVID-19 associated with newly diagnosed atrial fibrillation. Both patients were treated symptomatically for COVID-19 and discharged home after reverting to sinus rhythm. Physicians should be aware of the variable clinical presentations of COVID-19, especially in new or worsening cardiac illnesses, in order to practice the appropriate personal protection practices. More studies are needed to identify the viral mechanisms leading to the dysregulation of cardiac rhythm.", "qid": 22, "docid": "z4xb2ezo", "rank": 86, "score": 7.230000019073486}, {"content": "Title: 2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored Content: PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.", "qid": 22, "docid": "o988xoxn", "rank": 87, "score": 7.2154998779296875}, {"content": "Title: A Review of Acute Myocardial Injury in Coronavirus Disease 2019 Content: In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, Hubei province, China, and it has spread rapidly across the world, causing the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 infection predominantly results in pulmonary issues, accumulating evidence suggests the increased frequency of a variety of cardiovascular complications in patients with COVID-19. Acute cardiac injury, defined as elevated cardiac troponin levels, is the most reported cardiac abnormality in COVID-19 and strongly associated with mortality. In this article, we summarize the currently available data on the association of SARS-CoV-2 and COVID-19 with acute myocardial injury.", "qid": 22, "docid": "ja0wyr5w", "rank": 88, "score": 7.207900047302246}, {"content": "Title: COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ) Content: Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.", "qid": 22, "docid": "ihciswq4", "rank": 89, "score": 7.198800086975098}, {"content": "Title: COVID-19 and Acute Heart Failure: Screening the Critically Ill \u2013 A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ) Content: Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.", "qid": 22, "docid": "zl93fezj", "rank": 90, "score": 7.198799133300781}, {"content": "Title: A Nationwide Survey of UK cardiac surgeons view on clinical decision making during the COVID-19 pandemic Content: Background: No firm recommendations are currently available to guide decision making for patients requiring cardiac surgery during the COVID-19 pandemic. Systematic appraisal of national expert consensus can be used to generate interim recommendations until data from clinical observations will become available. Hence, we aimed to collect and quantitatively appraise nationwide UK senior surgeons opinion on clinical decision making for patients requiring cardiac surgery during the COVID-19 pandemic. Methods: We mailed a web-based questionnaire to all consultant cardiac surgeons through the Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS) mailing list on the 17th April 2020 and we pre-determined to close the survey on the 21st April 2020. This survey was primarily designed to gather information on UK surgeons opinion using 12 items. Strong consensus was predefined as an opinion shared by at least 60% of responding consultants. Results: A total of 86 consultant surgeons undertook the survey. All UK cardiac units were represented by at least one consultant. Strong consensus was achieved for the following key questions:1) before hospital admission every patient should receive nasopharyngeal swab, PCR and chest CT; 2) the use of full PPE should to be adopted in every case by the theatre team regardless patients COVID-19 status; 3) the risk of COVID-19 exposure for patients undergoing heart surgery should be considered moderate to high and likely to increase mortality if it occurs; 4) cardiac procedure should be decided based on ad-hoc multidisciplinary team discussion for every patient. The majority believed that both aortic and mitral surgery should be considered in selected cases. The role of CABG surgery during the pandemic was more controversial. Conclusions: In the current unprecedented scenario, the present survey provides information for generating interim recommendations until data from clinical observations will become available.", "qid": 22, "docid": "dgyvbarm", "rank": 91, "score": 7.1946001052856445}, {"content": "Title: Will the hidden specter of acute coronary syndrome (ACS) and ST-segment elevation myocardial infarction (STEMI) emerge from the avalanche of COVID-19? Content: There has been a huge impact of the COVID-19 pandemic on global healthcare systems. Advisories across the world have appealed to people to stay at home and observe social distancing to slow down the pandemic. However it is important to realize as to how this is affecting acute cardiovascular care. Recent studies from Europe and USA have reported &gt; 50% reduction in hospital admissions for ACS and declining rates of coronary interventions. The possible reasons for this noticeable reduction in patients with ACS/STEMI during the COVID-19 pandemic are multi-factorial. On one hand, it is due to change in thresholds for referring patients of ACS/STEMI for cardiac catheterization, with fibrinolysis being acceptable for many stable STEMI patients and conservative management being preferred for NSTEMI patients. Theories abound on how \u201cstaying at home\u201d strategy may have led to an reduction in acute coronary events due to healthier lifestyle, better compliance and reduced stress. Realistically however, a more disquieting reason would be a \u201cpseudo-reduction\u201d ie. the incidence of ACS/STEMI is actually the same, but these patients are staying away from hospitals due to fear of contracting the infection. Lockdown restrictions have also limited transport options for patients seeking to reach hospitals in time. Healthcare systems need to be prepared for an anticipated downstream deluge of such untreated patients who may present with sequelae like heart failure, reinfarction, arrhythmias, mechanical complications etc. Scientific societies should have proactive campaigns to alleviate patient concerns, and encourage them to seek timely medical attention despite the COVID-19 pandemic.", "qid": 22, "docid": "3df1gdeb", "rank": 92, "score": 7.173500061035156}, {"content": "Title: Cardiac complications in community-acquired pneumonia and COVID-19 Content: Community-acquired pneumonia (CAP) remains a global health problem with significant morbidity and mortality. Much recent published literature about the infection has indicated that a substantial number of patients with CAP, particularly those ill enough to be admitted to hospital, will suffer a cardiovascular event. While these may include events such as deep venous thrombosis and stroke, most of the events involve the heart and include the occurrence of an arrhythmia (most commonly atrial fibrillation), new onset or worsening of heart failure and acute myocardial infarction. While such cardiac events may occur, for example, in all-cause CAP and CAP due to influenza virus infection, and more recently described with the SARS-CoV-2 pandemic, a significant amount of research work has been investigating the pathogenic mechanisms of these cardiac events in patients with CAP due to Streptococcus pneumoniae (pneumococcus) and, more recently, COVID-19 infections. Such research has identified a number of mechanisms by which these microorganisms may cause cardiovascular events. Importantly, these cardiac events appear not only to be associated with in-hospital mortality, but they also appear to contribute to longer-term mortality of patients with CAP, even after their discharge from hospital. This review will focus initially on studies of cardiovascular events in all-cause CAP and pneumococcal CAP, excluding COVID-19 infection, and then address similar issues in the latter infection.", "qid": 22, "docid": "k0kud80s", "rank": 93, "score": 7.172999858856201}, {"content": "Title: Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study. Content: BACKGROUND The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60-74 years old) and old-old patients (\u226575 years old). METHODS In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared. RESULTS Of the 105 elderly patientsconfirmed withCOVID-19, 81.0% were young-old patients, and 19.0% were old-old patients; 54.3% of elderly patients were females. Overall, 69.5% of elderly patients had underlying diseases, and the most common comorbidities included hypertension (43.8%), diabetes (25.7%), and cardiac disease (16.2%). Of the elderly patients, 22.9% were severe and 10.5% were critical severe cases. On admission, the most frequent symptoms in elderly patients included fever (66.7%), cough (64.8%), and fatigue (33.3%). Lymphopenia (31.4%), increased D-dimer (38.1%), depressed albumin (36.2%), elevated lactate dehydrogenase (41.0%), and a high level of C-reactive protein (79.0%) were common among elderly patients with COVID-19. The median prothrombin time (PT) and the activated partial thromboplastin time (APTT) were longer in old-old patients than young-old patients (PT median 12.3 vs. 13.1 s, p = 0.007; APTT median 39.0 vs. 33.5 s, p = 0.045). Young-old patients showed fewer complications (14.1%) than old-old patients (40.0%; p = 0.0014) and fewer received invasive ventilator support (3.5 vs. 25.0%, p = 0.006). As of March 11, 2020, 85.7% of elderly patients had been discharged, 3 deaths had occurred, and 11.4% were still hospitalized. CONCLUSIONS Elderly patients usually have chronic medical illness and are likely to have a severe or critically severe condition. They could show atypical symptoms without fever or cough and multiple organ dysfunction. Old-old patients tend to have more complications than young-old patients during hospitalization. Careful nursing, observation, and systemic treatment are very important in elderly patients.", "qid": 22, "docid": "9jq9xedk", "rank": 94, "score": 7.170599937438965}, {"content": "Title: Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study Content: BACKGROUND: The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60-74 years old) and old-old patients (&#8805;75 years old). METHODS: In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared. RESULTS: Of the 105 elderly patientsconfirmed withCOVID-19, 81.0% were young-old patients, and 19.0% were old-old patients; 54.3% of elderly patients were females. Overall, 69.5% of elderly patients had underlying diseases, and the most common comorbidities included hypertension (43.8%), diabetes (25.7%), and cardiac disease (16.2%). Of the elderly patients, 22.9% were severe and 10.5% were critical severe cases. On admission, the most frequent symptoms in elderly patients included fever (66.7%), cough (64.8%), and fatigue (33.3%). Lymphopenia (31.4%), increased D-dimer (38.1%), depressed albumin (36.2%), elevated lactate dehydrogenase (41.0%), and a high level of C-reactive protein (79.0%) were common among elderly patients with COVID-19. The median prothrombin time (PT) and the activated partial thromboplastin time (APTT) were longer in old-old patients than young-old patients (PT median 12.3 vs. 13.1 s, p = 0.007; APTT median 39.0 vs. 33.5 s, p = 0.045). Young-old patients showed fewer complications (14.1%) than old-old patients (40.0%; p = 0.0014) and fewer received invasive ventilator support (3.5 vs. 25.0%, p = 0.006). As of March 11, 2020, 85.7% of elderly patients had been discharged, 3 deaths had occurred, and 11.4% were still hospitalized. CONCLUSIONS: Elderly patients usually have chronic medical illness and are likely to have a severe or critically severe condition. They could show atypical symptoms without fever or cough and multiple organ dysfunction. Old-old patients tend to have more complications than young-old patients during hospitalization. Careful nursing, observation, and systemic treatment are very important in elderly patients.", "qid": 22, "docid": "atfzbd4z", "rank": 95, "score": 7.170598983764648}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: The novel coronavirus 2019 disease (COVID-19) pandemic has placed intense pressure on health care organizations around the world. Among other concerns, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with preexisting cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent and, in some cases, prolonged rehabilitation needs after acute hospitalization. This report describes the current status of post-discharge cardiac care in Canada and provides suggestions regarding steps that policymakers and health care organizations can take to prepare for the COVID-19 pandemic.", "qid": 22, "docid": "8508n0ex", "rank": 96, "score": 7.156700134277344}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: Abstract The novel coronavirus 2019 (COVID-19) pandemic has placed intense pressure on healthcare organizations around the world. Amongst others, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with pre-existing cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent, and in some cases, prolonged rehabilitation needs following acute hospitalization. This manuscript describes the current status of post-discharge cardiac care in Canada and provides suggestions with regards to steps that policymakers and healthcare organizations can take to prepare for the COVID-19 pandemic.", "qid": 22, "docid": "8obqdbh9", "rank": 97, "score": 7.156699180603027}, {"content": "Title: 2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored Content: PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SUMMARY: SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.", "qid": 22, "docid": "uhmxkvit", "rank": 98, "score": 7.156400203704834}, {"content": "Title: ECMO application of patients with Critical Corona Virus Disease 2019 and fulminant myocarditis Content: Objective To evaluate the clinical experience of extracorporeal membrane oxygenation (ECMO) treatment on two cases of infection with the critical Corona Virus Disease 2019 (COVID-19) complicated by fulminant myocarditis (FM) Methods This study selects two COVID-19 cases comorbid with fulminant myocarditis and had been treated with ECMO in Shenzhen Third People's Hospital from January 2020 to February 2020 We compare the index of inflammation, immunization, D-dimer and lactic acid before and after ECMO treatment in 24 and 96 hours, cardiopulmonary function before and after ECMO treatment in 24, 48, 72, 96 hours, We also analyze the complications and clinical outcomes of the two cases during the ECMO treatment Results Both patients were elderly obese men with chronic cardiopulmonary disease Comparing the laboratory test results and imaging data of the two patients, the acute lung injury score, oxygenation index, albumin level, hypersensitive C-reactive protein, lactate and lactate dehydrogenase levels in 2 patients after ECMO treatment were improved as compared with those before ECMO treatment Finally, case 1 died of multiple organ failure and his cardiac function continued to deteriorate, while, case 2 successfully withdrew and his cardiac function gradually improved Conclusions For critical COVID-19 patients with fulminant myocarditis, ECMO treatment can improve pulmonary function in the short term, provide valuable time for rescuing COVID-19 patients with fulminant myocarditis", "qid": 22, "docid": "wlwt65w5", "rank": 99, "score": 7.131700038909912}, {"content": "Title: Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications Content: Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO Despite being mainly a respiratory virus, cardiac complications have been described These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19 The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications Received 6 April 2020 Accepted 14 April 2020 Correspondence to Antoine Fakhry AbdelMassih, MD, Pediatrics\u2019 Department, Pediatric Cardiology unit, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 12411, Egypt, E-mail: antoine abdelmassih@kasralainy edu eg \u00a9 2020Wolters Kluwer Health Lippincott Williams Wilkins", "qid": 22, "docid": "tkbctdyj", "rank": 100, "score": 7.1244001388549805}]}
{"query": "what kinds of complications related to COVID-19 are associated with hypertension?", "hits": [{"content": "Title: COVID-19: What are the risks in hypertensive patients? Content: Considering the number of patients affected by SARS-CoV-2, the World Health Organization declared a pandemic on 11 March 2020. A number of publications regarding the course of COVID-19 infection and its relation to comorbidities have appeared since December 2019, when the first cases of atypical pneumonia were diagnosed in China. There is evidence of the higher susceptibility and higher risk of unfavourable outcomes in comorbid patients, including those with hypertension. We summarize the available data on the association with the COVID-19 infection and arterial hypertension, and discuss potential risks, e. g. the risks and benefits of antihypertensive therapy (in particular, related to the blockers of renin-angiotensin-aldosterone system) and the management approaches.", "qid": 23, "docid": "ta9g9ceh", "rank": 1, "score": 9.729499816894531}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 23, "docid": "gwefujal", "rank": 2, "score": 9.400899887084961}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 23, "docid": "n4dgqo73", "rank": 3, "score": 9.400898933410645}, {"content": "Title: Can pioglitazone be potentially useful therapeutically in treating patients with covid-19? Content: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPAR\u03b3 agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.", "qid": 23, "docid": "9qpe4qm4", "rank": 4, "score": 8.643799781799316}, {"content": "Title: Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPAR\u00ce\u00b3 agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.", "qid": 23, "docid": "weyym7tx", "rank": 5, "score": 8.643798828125}, {"content": "Title: Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico Content: BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among 177,133 subjects at May 18(th), 2020, we observed 51,633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, COPD, advanced age, hypertension, immunosuppression, and CKD; we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age \u226565 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.823). RESULTS: Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.", "qid": 23, "docid": "xrmwpep6", "rank": 6, "score": 8.595199584960938}, {"content": "Title: Predicting Mortality Due to SARS-CoV-2: A Mechanistic Score Relating Obesity and Diabetes to COVID-19 Outcomes in Mexico Content: BACKGROUND: The SARS-CoV-2 outbreak poses a challenge to health care systems due to its high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity, and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of the Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19-related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among the 177\u00e2\u0080 133 subjects at the time of writing this report (May 18, 2020), we observed 51\u00e2\u0080 633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, chronic obstructive pulmonary disease, advanced age, hypertension, immunosuppression, and chronic kidney disease (CKD); we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for intensive care unit admission and intubation. Our predictive score for COVID-19 lethality included age\u00e2\u0080 &#8805;\u00e2\u0080 65 years, diabetes, early-onset diabetes, obesity, age\u00e2\u0080 <\u00e2\u0080 40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (C-statistic\u00e2\u0080 =\u00e2\u0080 0.823). CONCLUSIONS: Here, we propose a mechanistic approach to evaluate the risk for complications and lethality attributable to COVID-19, considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first-contact scenario.", "qid": 23, "docid": "ezny6ajo", "rank": 7, "score": 8.484399795532227}, {"content": "Title: A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine Content: Blacks/African Americans are overrepresented in the number of hospitalizations and deaths from COVID-19 in the United States, which could be explained through differences in the prevalence of existing comorbidities. We performed a disease-disease phenome-wide association study (PheWAS) using data representing 5,698 COVID-19 patients from a large academic medical center, stratified by race. We explore the association of 1,043 pre-occurring conditions with several COVID-19 outcomes: testing positive, hospitalization, ICU admission, and mortality. Obesity, iron deficiency anemia and type II diabetes were associated with susceptibility in the full cohort, while ill-defined descriptions/complications of heart disease and stage III chronic kidney disease were associated among non-Hispanic White (NHW) and non-Hispanic Black/African American (NHAA) patients, respectively. The top phenotype hits in the full, NHW, and NHAA cohorts for hospitalization were acute renal failure, hypertension, and insufficiency/arrest respiratory failure, respectively. Suggestive relationships between respiratory issues and COVID-19-related ICU admission and mortality were observed, while circulatory system diseases showed stronger association in NHAA patients. We were able to replicate some known comorbidities related to COVID-19 outcomes while discovering potentially unknown associations, such as endocrine/metabolic conditions related to hospitalization and mental disorders related to mortality, for future validation. We provide interactive PheWAS visualization for broader exploration.", "qid": 23, "docid": "915x3q19", "rank": 8, "score": 8.476400375366211}, {"content": "Title: Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association\u2013European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.", "qid": 23, "docid": "3bvtcdja", "rank": 9, "score": 8.369199752807617}, {"content": "Title: Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.", "qid": 23, "docid": "ln9xw11k", "rank": 10, "score": 8.3691987991333}, {"content": "Title: Excerpts from the documents of Mexican positions and recommendations in cardiovascular diseases and COVID-19. Content: The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic. Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation. The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19.", "qid": 23, "docid": "r3krlegp", "rank": 11, "score": 8.319700241088867}, {"content": "Title: Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia Content: COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events. The patient described experienced unusually rapid development of pulmonary hypertension (PH) and right ventricular failure after recent severe COVID-19 pneumonia with cytokine release syndrome, which initially was successfully treated with methylprednisolone and tocilizumab. The development of pulmonary hypertension and right ventricular failure \u2013 in the absence of emboli on multiple CT angiograms \u2013 was most likely caused by progressive pulmonary parenchymal abnormalities combined with microvascular damage of the pulmonary arteries (group III and IV pulmonary hypertension, respectively). To the best of our knowledge, these complications have not previously been described and therefore awareness of PH as a complication of COVID-19 is warranted. LEARNING POINTS: COVID-19 increasingly presents with systemic and multi-organ involvement with vascular, thromboembolic and cardiac events. Patients with severe COVID-19 pneumonia and concomitant cytokine release syndrome may be particularly at risk for the development of secondary pulmonary hypertension and right ventricular failure. Pulmonary hypertension can develop unusually rapidly following COVID-19 pneumonia and probably results from progressive pulmonary interstitial and microvascular abnormalities due to COVID-19.", "qid": 23, "docid": "7xqmuoye", "rank": 12, "score": 8.318599700927734}, {"content": "Title: Extractos de los documentos de posicionamientos y recomendaciones mexicanas en enfermedades cardiovasculares y COVID-19./ Excerpts from the documents of Mexican positions and recommendations in cardiovascular diseases and COVID-19 Content: The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic. Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation. The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19.", "qid": 23, "docid": "thx2xtsl", "rank": 13, "score": 8.246899604797363}, {"content": "Title: Extractos de los documentos de posicionamientos y recomendaciones mexicanas en enfermedades cardiovasculares y COVID-19 Content: The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19", "qid": 23, "docid": "p7ldfrbv", "rank": 14, "score": 8.231599807739258}, {"content": "Title: Biomarkers for Chronic Kidney Disease Associated with High Salt Intake Content: High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension. In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a \u201csilent\u201d manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage. Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals. Recently, several new biomarkers for damage of renal tubular epithelia such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) have been identified. Previously, we found a novel renal biomarker, urinary vanin-1, in several animal models with renal tubular injury. However, there are few studies about early biomarkers of the progression to CKD associated with a high-salt diet. This review presents some new insights about these novel biomarkers for CKD in normotensives and hypertensives under a high salt intake. Interestingly, our recent reports using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high-salt diet revealed that urinary vanin-1 and NGAL are earlier biomarkers of renal tubular damage in SHR and WKY, whereas urinary Kim-1 is only useful as a biomarker of salt-induced renal injury in SHR. Clinical studies will be needed to clarify these findings.", "qid": 23, "docid": "i3ydg93k", "rank": 15, "score": 8.226900100708008}, {"content": "Title: COVID-19 and arterial hypertension: Hypothesis or evidence? Content: Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID-19). Hypertension appeared consistently as the most prevalent risk factors in COVID-19 patients. Some investigations speculated about the association between renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID-19. There are only a few follow-up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID-19 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID-19 and the role of hypertension on outcome in these patients.", "qid": 23, "docid": "9nbj3ckb", "rank": 16, "score": 8.15839958190918}, {"content": "Title: COVID\u201019 and arterial hypertension: Hypothesis or evidence? Content: Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID\u201019). Hypertension appeared consistently as the most prevalent risk factors in COVID\u201019 patients. Some investigations speculated about the association between renin\u2010angiotensin\u2010aldosterone system (RAAS) and susceptibility to COVID\u201019, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID\u201019. There are only a few follow\u2010up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID\u201019 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID\u201019 and the role of hypertension on outcome in these patients.", "qid": 23, "docid": "hzb2fkj5", "rank": 17, "score": 8.158398628234863}, {"content": "Title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Content: BACKGROUND AND AIMS: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). METHODS: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. CONCLUSION: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "qid": 23, "docid": "1y78dfsl", "rank": 18, "score": 8.081600189208984}, {"content": "Title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Content: Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "qid": 23, "docid": "7kw9lws0", "rank": 19, "score": 8.081599235534668}, {"content": "Title: Contemporary and Future Concepts on Hypertension in African Americans: COVID-19 and Beyond Content: BACKGROUND: Cardiovascular disease related mortality is the leading cause of death in the United States, with hypertension being the most prevalent and potent risk factor. For decades hypertension has disproportionately affected African Americans, who also have a higher burden of associated comorbidities including diabetes and heart failure. METHODS: Current literature including guideline reports and newer studies on hypertension in African Americans in PubMed were reviewed. We also reviewed newer publications on the relationship between COVID-19 and cardiovascular disease. FINDINGS: While APOL1 has been theorized in the epidemiology of hypertension, the increased prevalence and associated risks are primarily due to environmental and lifestyle factors. These factors include poor diet, adverse lifestyle, and social determinants. Hypertension control can be achieved by lifestyle modifications such as low sodium diet, weight loss, and adequate physical activity. When lifestyle modifications alone do not adequately control hypertension, a common occurrence among African Americans who suffer with greater prevalence of resistant hypertension, pharmacological intervention is indicated. The efficacy of renal denervation, and the use of sodium-glucose cotransporter 2 and aminopeptidase A inhibitors, have been studied for treatment of resistant hypertension. Furthermore, the recent COVID-19 crisis has been particularly devastating among African Americans who demonstrate increased incidence and poorer health outcomes related to the disease. CONCLUSION: The disparities in outcomes, which are largely attributable to a greater prevalence of comorbidities such as hypertension and obesity, in addition to adverse environmental and socioeconomic factors, highlight the necessity of specialized clinical approaches and programs for African Americans to address longstanding barriers to equitable care.", "qid": 23, "docid": "cn2j9ih4", "rank": 20, "score": 8.076299667358398}, {"content": "Title: Mechanism of inflammatory response in associated comorbidities in COVID-19 Content: BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.", "qid": 23, "docid": "cn3bpmwj", "rank": 21, "score": 8.069499969482422}, {"content": "Title: Hypertension, the renin\u2013angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence Content: Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin\u2013angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "qid": 23, "docid": "y4h95kb4", "rank": 22, "score": 8.004400253295898}, {"content": "Title: COVID-19, hypertension and cardiovascular diseases: Should we change the therapy? Content: The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.", "qid": 23, "docid": "bwkad2s0", "rank": 23, "score": 7.973800182342529}, {"content": "Title: Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients. Content: Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.", "qid": 23, "docid": "95wclabe", "rank": 24, "score": 7.938899993896484}, {"content": "Title: Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19 Content: Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "qid": 23, "docid": "69qefbbo", "rank": 25, "score": 7.924799919128418}, {"content": "Title: Role of MicroRNA in Endothelial Dysfunction and Hypertension Content: PURPOSE OF REVIEW: Hypertension is either a cause or a consequence of the endothelial dysfunction and a major risk factor for cardiovascular disease (CVD). In vitro and in vivo studies established that microRNAs (miRNAs) are decisive for endothelial cell gene expression and function in various pathological conditions associated with CVD. This review provides an overview of the miRNA role in controlling the key connections between endothelial dysfunction and hypertension. RECENT FINDINGS: Herein we summarize the present understanding of mechanisms underlying hypertension and its associated endothelial dysfunction as well as the miRNA role in endothelial cells with accent on the modulation of renin-angiotensin-aldosterone-system, nitric oxide, oxidative stress and on the control of vascular inflammation and angiogenesis in relation to endothelial dysfunction in hypertension. In particular, latest insights in the identification of endothelial-specific microRNAs and their targets are added to the understanding of miRNA significance in hypertension. SUMMARY: This comprehensive knowledge of the role of miRNAs in endothelial dysfunction and hypertension and of molecular mechanisms proposed for miRNA actions may offer novel diagnostic biomarkers and therapeutic targets for controlling hypertension-associated endothelial dysfunction and other cardiovascular complications.", "qid": 23, "docid": "az2t6jjx", "rank": 26, "score": 7.904699802398682}, {"content": "Title: Diabetes and COVID\u201019: psychosocial consequences of the COVID\u201019 pandemic in people with diabetes in Denmark\u2014what characterizes people with high levels of COVID\u201019\u2010related worries? Content: AIM: To map COVID\u201019\u2010specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID\u201019 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID\u201019 pandemic. METHODS: A cross\u2010sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID\u201019\u2010specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes\u2010specific social support, diabetes distress and changes in diabetes\u2010specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID\u201019\u2010specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID\u201019, about one\u2010third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID\u201019 and diabetes. CONCLUSION: People with diabetes have COVID\u201019\u2010specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID\u201019 and diabetes.", "qid": 23, "docid": "3jolt83r", "rank": 27, "score": 7.904200077056885}, {"content": "Title: Diabetes and COVID-19: psychosocial consequences of the COVID-19 pandemic in people with diabetes in Denmark-what characterizes people with high levels of COVID-19-related worries? Content: AIM: To map COVID-19-specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID-19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID-19-specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes-specific social support, diabetes distress and changes in diabetes-specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID-19-specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID-19, about one-third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID-19 and diabetes. CONCLUSION: People with diabetes have COVID-19-specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID-19 and diabetes.", "qid": 23, "docid": "hycd9zua", "rank": 28, "score": 7.904199123382568}, {"content": "Title: Is the epidemic spread related to GDP? Visualizing the distribution of COVID-19 in Chinese Mainland Content: In December 2019, COVID-19 were detected in Wuhan City, Hubei Province of China. SARS-CoV-2 rapidly spread to the whole Chinese mainland with the people during the Chinese Spring Festival Travel Rush. As of 19 February 2020, 74576 confirmed cases of COVID-19 had been reported in Chinese Mainland. What kind of cities have more confirmed cases, and is there any relationship between GDP and confirmed cases? In this study, we explored the relationship between the confirmed cases of COVID-19 and GDP at the prefectural-level, found a positive correlation between them. This finding warns high GDP areas should pay more prevention and control efforts when an epidemic outbreak, as they have greater risks than other areas nearby.", "qid": 23, "docid": "go442ycb", "rank": 29, "score": 7.867599964141846}, {"content": "Title: Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors Content: INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "qid": 23, "docid": "bwg3tzx8", "rank": 30, "score": 7.857699871063232}, {"content": "Title: Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors: Content: Abstract Introduction There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. Methods Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. Results 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 \u2013 0.88). A similar albeit not significant trend was observed for ACEI. Conclusion ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "qid": 23, "docid": "wxpfg25n", "rank": 31, "score": 7.857698917388916}, {"content": "Title: Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney Content: Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter individual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.", "qid": 23, "docid": "uyyd1m1p", "rank": 32, "score": 7.83050012588501}, {"content": "Title: Impact of Chronic Comorbidities on Progression and Prognosis in Patients with COVID-19: A Retrospective Cohort Study in 1031 Hospitalized Cases in Wuhan, China Content: Background The recent outbreak of COVID-19 has rapidly spread worldwide. A large proportion of COVID-19 patients with chronic underlying complications have been reported to be in severe condition and show unpromising clinical outcomes. But whether chronic comorbidities are risk factors affecting the severity of COVID-19 has not been well described. Methods We included COVID-19 patients who had been admitted to Tongji Hospital, Tongji medical college of HUST (Wuhan, China) from January, 27, 2020 to March, 8, 2020 in this retrospective cohort study. The final date of follow-up was March, 30, 2020. All patients were diagnosed with COVID-19 according to Prevention and control Scheme for Novel Coronavirus Pneumonia published by National Health Commission of the People' s Republic of China and WHO interim. Demographic data, medical history, clinical symptoms and signs, laboratory findings, chest computed tomography (CT), treatment and clinical outcomes were extracted from electronic medical records with standardized data collection forms and compared among different groups. Results 1031 COVID-19 inpatients were included in this study, of whom 866 were discharged and 165 were dead in hospital. 73% of 165 dead patients had complicated chronic comorbidities. Of the 1031 patients, 514 (50%) were combined with chronic comorbidities, and showed CFR 2.8 times as that of patients without any underlying disease. The number of patients with hypertension accounted for three fourths of those with concomitant underlying diseases. The univariable regression revealed that patients in the simple hypertension group showed overall risk higher than those in the simple diabetes mellitus group. In the age-grouped research, patients in the hypertension senile group were proved to be at the highest risk, which might be associated with the level of LDH and eGFR. In this retrospective cohort study, 166 (43%) patients with hypertension took CCB during the hospitalization, the odds ratio of CFR in patients with hypertension taking CCB group was 0.68 (P = 0.155), compared to those not. Conclusion Our data shows that the clinical manifestations of most hospitalized patients with COVID-19 are actually systemic syndromes, although COVID-19 is defined as novel coronavirus pneumonia in China. Hypertension is not just a chronic underlying comorbidity, but also a risk factor affecting the severity of COVID-19 and does play a critical role in improving patients' clinical outcomes. Therefore, hypertension management in patients with COVID-19 should be a major challenge in the diagnostic and therapeutic strategies, including optimal management of blood pressure and pathophysiological status.", "qid": 23, "docid": "d7q7m7zz", "rank": 33, "score": 7.803400039672852}, {"content": "Title: Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression Content: BACKGROUND AND AIMS: Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. METHODS: Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. RESULTS: There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age &#8805;55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension &#8805;25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) CONCLUSION: DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.", "qid": 23, "docid": "hj5zcw2v", "rank": 34, "score": 7.799099922180176}, {"content": "Title: Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia \u2013 A systematic review, meta-analysis, and meta-regression Content: Abstract Background and aims Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. Methods Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. Results There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age \u226555 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension \u226525% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) Conclusion DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.", "qid": 23, "docid": "u6uqroi0", "rank": 35, "score": 7.799098968505859}, {"content": "Title: Disparities in Vulnerability to Severe Complications from COVID-19 in the United States Content: This paper provides the first nationally representative estimates of vulnerability to severe complications from COVID-19 overall and across race-ethnicity and socioeconomic status. We use the Panel Study of Income Dynamics (PSID) to examine the prevalence of specific health conditions associated with complications from COVID-19 and to calculate, for each individual, an index of the risk of severe complications from respiratory infections developed by DeCaprio et al. (2020). We show large disparities across race-ethnicity and socioeconomic status in the prevalence of conditions, including hypertension, which are associated with the risk of severe complications from COVID-19. Moreover, we show that these disparities emerge early in life, prior to age 65, leading to higher vulnerability to such complications. Our results suggest particular attention should be paid to the risk of adverse outcomes in midlife for non-Hispanic blacks, adults with a high school degree or less, and low-income Americans.", "qid": 23, "docid": "qk0cyee2", "rank": 36, "score": 7.720799922943115}, {"content": "Title: COVID\u201019 and Older Adults: What We Know Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), a novel virus that causes COVID\u201019 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin\u2010converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE\u20102 receptor, the very receptor that the SARS\u2010CoV\u20102 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID\u201019 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID\u201019 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926\u2013929, 2020", "qid": 23, "docid": "kd4uxcve", "rank": 37, "score": 7.683199882507324}, {"content": "Title: COVID-19 and Older Adults: What We Know Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes COVID-19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor that the SARS-CoV-2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID-19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID-19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926-929, 2020.", "qid": 23, "docid": "vhfl6l6k", "rank": 38, "score": 7.683198928833008}, {"content": "Title: Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study Content: AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17\u20133.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03\u20134.57, P = 0.041). The mortality rates were similar between the renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28\u20132.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45\u20130.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.", "qid": 23, "docid": "2nftsv4f", "rank": 39, "score": 7.679599761962891}, {"content": "Title: Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study Content: AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.", "qid": 23, "docid": "gjahdnay", "rank": 40, "score": 7.679598808288574}, {"content": "Title: Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India Content: BACKGROUND AND AIMS: During the current pandemic of COVID-19 India is under lockdown which could cause disruption in diet and lifestyle in patients with type 2 diabetes (T2DM). We aimed to study lifestyle changes and other common issues related to treatment in our previously seen and treated patients with T2DM. METHODS: Patients (n, 150) who were regularly following up before lockdown were interviewed telephonically (after 45 days of start of lockdown) regarding lifestyle changes, stress and other diabetes-related questions. RESULT: Carbohydrate consumption and frequency of snacking increased in 21% and 23% patients, respectively. Interestingly, 27% patients reported an increase in consumption of fruits. Exercise duration was reduced in 42% and weight gain occurred in 19% patients. Frequency of doing self-monitoring of blood glucose (SMBG) was decreased in 23% patients. \u2018Mental stress\u2019 of any kind was reported in 87% patients. Availability of medicine and insulin was uninterrupted in 91% patients. Knowledge about telemedicine was present in 69% and majority (92%) of these patients preferred video consultation. CONCLUSION: During 45 days of lockdown increase in carbohydrate intake, decrease in exercise, decreased SMBG and widespread mental stress in patients with T2DM was seen, factors which may destabilize or exacerbate hyperglycemia and hypertension. Some positive changes (e.g. increased intake of fruits) were also observed.", "qid": 23, "docid": "keseey9x", "rank": 41, "score": 7.666600227355957}, {"content": "Title: Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India Content: BACKGROUND AND AIMS: During the current pandemic of COVID-19, India is under lockdown which could cause disruption in diet and lifestyle in patients with type 2 diabetes (T2DM). We aimed to study lifestyle changes and other common issues related to treatment in our previously seen and treated patients with T2DM. METHODS: Patients (n, 150) who were regularly following up before lockdown were interviewed telephonically (after 45 days of start of lockdown) regarding lifestyle changes, stress and other diabetes-related questions. RESULT: Carbohydrate consumption and frequency of snacking increased in 21% and 23% patients, respectively. Interestingly, 27% patients reported an increase in consumption of fruits. Exercise duration was reduced in 42% and weight gain occurred in 19% patients. Frequency of doing self-monitoring of blood glucose (SMBG) was decreased in 23% patients. 'Mental stress' of any kind was reported in 87% patients. Availability of medicines and insulin was uninterrupted in 91% patients. Knowledge about telemedicine was present in 69% and majority (92%) of these patients preferred video consultation. CONCLUSION: During 45 days of lockdown increase in carbohydrate intake, decrease in exercise, decreased SMBG and widespread mental stress in patients with T2DM was recorded, factors which may destabilize or exacerbate hyperglycemia and hypertension. Some positive changes (e.g. increased intake of fruits) were also observed.", "qid": 23, "docid": "s1eo9qdi", "rank": 42, "score": 7.666599273681641}, {"content": "Title: Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives Content: BACKGROUND: The effect of chronic use of renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9(th) and 31(st) March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "qid": 23, "docid": "82m84n4w", "rank": 43, "score": 7.665599822998047}, {"content": "Title: Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives Content: BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "qid": 23, "docid": "w2bhtu9f", "rank": 44, "score": 7.6655988693237305}, {"content": "Title: Stent-Assisted Coiling of 501 Wide-Necked Intracranial Aneurysms: A Single-Center 8-Year Experience. Content: BACKGROUND Stent-assisted coiling has expanded the treatment of complex wide-necked intracranial aneurysms. We present our experience with stent-assisted coiling, with an emphasis on procedure-related neurologic complications and the incidence of angiographic recurrence. METHODS A total of 480 patients with 501 aneurysms who were treated with stent-assisted coiling between January 2007 and December 2014 were reviewed retrospectively. Baseline characteristics, procedure-related complications, angiographic follow-up results, and clinical outcomes were statistically analyzed. RESULTS Among the 480 patients, 423 (88%) were treated electively and 57 (11%) were treated in the context of subarachnoid hemorrhage. There were 22 (4.58%) overall procedure-related complications, which caused death in 4 patients (0.83%) and morbidity in 4 patients (0.83%). In a logistic regression analysis, the complications differed significantly among the patients with hypertension (odds ratio [OR], 2.85; 95% confidence interval [CI], 1.09-7.48; P = 0.03), patients with aneurysms treated with coiling before stenting (OR, 3.07; 95% CI, 1.07-8.81; P = 0.04), and patients treated with multiple stents (OR, 4.96; 95% CI, 1.02-24.07; P = 0.04). Angiographic follow-up was available for 396 patients (83.4%) for a mean of 13 months. The rates of recanalization and retreatment were 13.9% and 3.5%, respectively. In a logistic analysis, larger aneurysm size and initial incomplete aneurysm occlusion were predictors of recanalization. Clinical follow-up was available for 406 patients (85.6%) for a mean of 44.8 months, and 399 patients (98.3%) achieved a Glasgow Outcome Scale score of 5. CONCLUSIONS Stent-assisted coiling appears to be a safe and effective option for treating complex wide-necked aneurysms. Higher complication rates are associated with coiling before stenting, use of multiple stents, and hypertension. Stent delivery before coil deployment reduces the risk of procedural complications. Larger aneurysm size and initial incomplete occlusion are associated with aneurysm recanalization.", "qid": 23, "docid": "i85i6tep", "rank": 45, "score": 7.648099899291992}, {"content": "Title: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis Content: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.", "qid": 23, "docid": "mez1k8t0", "rank": 46, "score": 7.639500141143799}, {"content": "Title: Hypertension among adults living in Haiti: An integrative review. Content: AIMS AND OBJECTIVES To determine what is known about hypertension among adults living in Haiti. BACKGROUND Hypertension is the leading cause of morbidity, the identified cause of heart failure in 45% of patients and is associated with more than 70% of cardiovascular disease-related hospital admissions in Haiti. DESIGN An integrative review of the literature. METHODS Searching four databases from 2007 to 2018, Whittemore and Knafl's method was used to review the literature. Three nurse researchers independently reviewed and appraised each publication applying the Johns Hopkins Evidence-based Practice Appraisal tool. RESULTS Eight publications were identified and appraised for level and quality of evidence. The synthesis of the literature yielded common themes of (i) high prevalence of hypertension among adults living in rural areas, (ii) public health challenges, (iii) lack of knowledge and awareness of hypertension and (iv) barriers to effective treatment. CONCLUSION Hypertension is a highly prevalent disease in Haiti that is understudied and warrants attention. To better serve this vulnerable population, culturally tailored prevention strategies and disease management programmes are recommended. RELEVANCE TO CLINICAL PRACTICE There is a lack of quality evidence to guide nurses in the management of hypertension for this vulnerable population. Identification of barriers to effective treatment among this underserved population will assist nurses and other healthcare professionals in identifying best possible practices for patient care in clinical settings across Haiti.", "qid": 23, "docid": "bc26pz53", "rank": 47, "score": 7.637499809265137}, {"content": "Title: A Proposed Plan for Prenatal Care to Minimize Risks of COVID-19 to Patients and Providers: Focus on Hypertensive Disorders of Pregnancy Content: Hypertensive disorders are the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and death. The detection of elevated blood pressure during pregnancy is one of the cardinal aspects of optimal antenatal care. With the outbreak of novel coronavirus disease 2019 (COVID-19) and the risk for person-to-person spread of the virus, there is a desire to minimize unnecessary visits to health care facilities. Women should be classified as low risk or high risk for hypertensive disorders of pregnancy and adjustments can be accordingly made in the frequency of maternal and fetal surveillance. During this pandemic, all pregnant women should be encouraged to obtain a sphygmomanometer. Patients monitored for hypertension as an outpatient should receive written instructions on the important signs and symptoms of disease progression and provided contact information to report the development of any concern for change in status. As the clinical management of gestational hypertension and preeclampsia is the same, assessment of urinary protein is unnecessary in the management once a diagnosis of a hypertensive disorder of pregnancy is made. Pregnant women with suspected hypertensive disorders of pregnancy and signs and symptoms associated with the severe end of the disease spectrum (e.g., headaches, visual symptoms, epigastric pain, and pulmonary edema) should have an evaluation including complete blood count, serum creatinine level, and liver transaminases (aspartate aminotransferase and alanine aminotransferase). Further, if there is any evidence of disease progression or if acute severe hypertension develops, prompt hospitalization is suggested. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and The Society for Maternal-Fetal Medicine (SMFM) for management of preeclampsia with severe features suggest delivery after 34 (0/7) weeks of gestation. With the outbreak of COVID-19, however, adjustments to this algorithm should be considered including delivery by 30 (0/7) weeks of gestation in the setting of preeclampsia with severe features. Key Points: Outbreak of novel coronavirus disease 2019 (COVID-19) warrants fewer office visits. Women should be classified for hypertension risk in pregnancy. Earlier delivery suggested with COVID-19 and hypertensive disorder.", "qid": 23, "docid": "i7vtddsj", "rank": 48, "score": 7.63539981842041}, {"content": "Title: A Proposed Plan for Prenatal Care to Minimize Risks of COVID-19 to Patients and Providers: Focus on Hypertensive Disorders of Pregnancy Content: Hypertensive disorders are the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and death. The detection of elevated blood pressure during pregnancy is one of the cardinal aspects of optimal antenatal care. With the outbreak of novel coronavirus disease 2019 (COVID-19) and the risk for person-to-person spread of the virus, there is a desire to minimize unnecessary visits to health care facilities. Women should be classified as low risk or high risk for hypertensive disorders of pregnancy and adjustments can be accordingly made in the frequency of maternal and fetal surveillance. During this pandemic, all pregnant women should be encouraged to obtain a sphygmomanometer. Patients monitored for hypertension as an outpatient should receive written instructions on the important signs and symptoms of disease progression and provided contact information to report the development of any concern for change in status. As the clinical management of gestational hypertension and preeclampsia is the same, assessment of urinary protein is unnecessary in the management once a diagnosis of a hypertensive disorder of pregnancy is made. Pregnant women with suspected hypertensive disorders of pregnancy and signs and symptoms associated with the severe end of the disease spectrum (e.g., headaches, visual symptoms, epigastric pain, and pulmonary edema) should have an evaluation including complete blood count, serum creatinine level, and liver transaminases (aspartate aminotransferase and alanine aminotransferase). Further, if there is any evidence of disease progression or if acute severe hypertension develops, prompt hospitalization is suggested. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and The Society for Maternal-Fetal Medicine (SMFM) for management of preeclampsia with severe features suggest delivery after 34 0/7 weeks of gestation. With the outbreak of COVID-19, however, adjustments to this algorithm should be considered including delivery by 30 0/7 weeks of gestation in the setting of preeclampsia with severe features. KEY POINTS: \u00b7 Outbreak of novel coronavirus disease 2019 (COVID-19) warrants fewer office visits.. \u00b7 Women should be classified for hypertension risk in pregnancy.. \u00b7 Earlier delivery suggested with COVID-19 and hypertensive disorder..", "qid": 23, "docid": "mnxmb5pz", "rank": 49, "score": 7.635398864746094}, {"content": "Title: State-of-the-Art Review: Hypertension Practice Guidelines in the Era of COVID-19 Content: The global burden of hypertension (HTN) is immense and increasing. In fact, HTN is the leading risk factor for adverse cardiovascular disease outcomes. Due to the critical significance and increasing prevalence of the disease, several national and international societies have recently updated their guidelines for the diagnosis and treatment of HTN. In consideration of the COVID-19 pandemic, this report provides clinicians with the best strategies to prevent HTN, manage the acute and long-term cardiac complications of HTN, and provide the best evidence-based care to patients in an ever-changing healthcare environment. The overarching goal of the various HTN guidelines is to provide easily accessible information to healthcare providers and public health officials, which is key for optimal clinical practice. However, the COVID-19 pandemic has challenged the ability to provide safe care to the most vulnerable hypertensive populations throughout the world. Therefore, this review compares the most recent guidelines of the 2017 American College of Cardiology/American Heart Association and multiple U.S. societies, the 2018 European Society of Cardiology/European Society of Hypertension, the 2019 National Institute for Care and Health Excellence, and the 2020 International Society of Hypertension. While a partial emphasis is placed on the management of HTN in the midst of COVID-19, this review will summarize current concepts and emerging data from the listed HTN guidelines on the diagnosis, monitoring, management, and evidence-based treatments in adults.", "qid": 23, "docid": "3kxn8l2e", "rank": 50, "score": 7.62939977645874}, {"content": "Title: Cholesterol in relation to covid\u201019: Should we care about it? Content: Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) causing corona virus disease\u201019 (COVID\u201019) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid\u2010lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID\u201019 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin\u2010converting enzyme 2 (ACE2) receptors for the S\u2010protein of SARS\u2010CoV\u20102. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol\u2010lowering therapies in reducing viral infectivity. In addition to their lipid\u2010lowering and plaque\u2010stabilisation effects, statins possess pleiotropic effects including anti\u2010inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS\u2010CoV\u20102 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID\u201019.", "qid": 23, "docid": "tdjkkeh2", "rank": 51, "score": 7.629000186920166}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge Content: BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS: This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19 METHODS: The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy RESULTS: The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue;while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19 CONCLUSIONS: The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress", "qid": 23, "docid": "lqfzte7w", "rank": 52, "score": 7.592599868774414}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge. Content: BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.", "qid": 23, "docid": "r4c7nldn", "rank": 53, "score": 7.592598915100098}, {"content": "Title: Incidence of acute kidney injury and its association with mortality in patients with COVID-19: a meta-analysis Content: Acute kidney injury (AKI) is a complication of COVID-19. However, the incidence of AKI in COVID-19 varies among studies. Thus, we aimed to evaluate the pooled incidence of AKI and its association with mortality in patients with COVID-19 using a meta-analysis. We search Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible publications reporting the clinical characteristics of patients with COVID-19 without language restriction. Incidence of AKI and mortality were reported. Meta-regression was used to describe the association between outcomes. From 26 studies (n=5497), the pooled incidence of AKI in patients with COVID-19 was 8.4% (95% CI 6.0% to 11.7%) with a pooled incidence of renal replacement therapy of 3.6% (95% CI 1.8% to 7.1%). The incidence of AKI was higher in critically ill patients (19.9%) compared with hospitalized patients (7.3%). The pooled estimated odds ratio for mortality from AKI was 13.33 (95% CI 4.05 to 43.91). No potential publication bias was detected. By using meta-regression analyses, the incidence of AKI was positively associated with mortality after adjusted for age and sex (Q=26.18; p=0.02). Moreover, age (p<0.01), diabetes (p=0.02), hypertension (p<0.01) and baseline serum creatinine levels (p=0.04) were positively associated with AKI incidence in adjusted models. In conclusion, AKI is present in 8.3% of overall patients with COVID-19 and in 19.9% of critically ill patients with COVID-19. Presence of AKI is associated with 13-fold increased risk of mortality. Age, diabetes, hypertension, and baseline serum creatinine levels are associated with increased AKI incidence.", "qid": 23, "docid": "0591zxc7", "rank": 54, "score": 7.562099933624268}, {"content": "Title: Incidence of acute kidney injury and its association with mortality in patients with COVID-19: a meta-analysis. Content: Acute kidney injury (AKI) is a complication of COVID-19. However, the incidence of AKI in COVID-19 varies among studies. Thus, we aimed to evaluate the pooled incidence of AKI and its association with mortality in patients with COVID-19 using a meta-analysis. We search Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible publications reporting the clinical characteristics of patients with COVID-19 without language restriction. Incidence of AKI and mortality were reported. Meta-regression was used to describe the association between outcomes. From 26 studies (n=5497), the pooled incidence of AKI in patients with COVID-19 was 8.4% (95% CI 6.0% to 11.7%) with a pooled incidence of renal replacement therapy of 3.6% (95% CI 1.8% to 7.1%). The incidence of AKI was higher in critically ill patients (19.9%) compared with hospitalized patients (7.3%). The pooled estimated odds ratio for mortality from AKI was 13.33 (95% CI 4.05 to 43.91). No potential publication bias was detected. By using meta-regression analyses, the incidence of AKI was positively associated with mortality after adjusted for age and sex (Q=26.18; p=0.02). Moreover, age (p<0.01), diabetes (p=0.02), hypertension (p<0.01) and baseline serum creatinine levels (p=0.04) were positively associated with AKI incidence in adjusted models. In conclusion, AKI is present in 8.3% of overall patients with COVID-19 and in 19.9% of critically ill patients with COVID-19. Presence of AKI is associated with 13-fold increased risk of mortality. Age, diabetes, hypertension, and baseline serum creatinine levels are associated with increased AKI incidence.", "qid": 23, "docid": "pqr593us", "rank": 55, "score": 7.562098979949951}, {"content": "Title: News and Perspectives Is There an Association Between Oral Health and Severity of COVID-19 Complications? Content: Most patients with severe complications from COVID-19 have underlying conditions such as obesity, diabetes, and hypertension. In parallel, there is growing evidence for a link between periodontitis and non-oral systemic diseases. The oral cavity is also a reservoir for respiratory pathogens, and patients with periodontal disease are more likely to develop hospital-acquired pneumonia than healthy individuals. We therefore hypothesize that improving oral health could decrease the severity of COVID-19 symptoms and reduce the associated morbidity.", "qid": 23, "docid": "a91obysp", "rank": 56, "score": 7.554800033569336}, {"content": "Title: Cardiovascular comorbidities and complications associated with coronavirus disease 2019 Content: Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "qid": 23, "docid": "o6a30irm", "rank": 57, "score": 7.54040002822876}, {"content": "Title: COVID-19 does not stop obstetrics: what we need to change to go on safely birthing. The experience of a University Obstetrics and Gynecology Department in Milan. Content: Since SARS-COV-2 appeared in Wuhan City, China and rapidly spread throughout Europe, a real revolution occurred in the daily routine and in the organization of the entire health system. While non-urgent clinical services have been reduced as far as possible, all kind of specialists turned into COVID-19 specialists. Obstetric assistance cannot be suspended and, at the same time, safety must be guaranteed. In addition, as COVID-19 positive pregnant patients require additional care, some of the clinical habits need to be changed to face emerging needs for a vulnerable but unstoppable kind of patients. We report the management set up in an Obstetrics and Gynecology Unit during the COVID-19 era in a University Hospital in Milan, Italy.", "qid": 23, "docid": "jf9whlu7", "rank": 58, "score": 7.4791998863220215}, {"content": "Title: COVID-19 does not stop obstetrics: what we need to change to go on safely birthing. The experience of a University Obstetrics and Gynecology Department in Milan Content: Since SARS-COV-2 appeared in Wuhan City, China and rapidly spread throughout Europe, a real revolution occurred in the daily routine and in the organization of the entire health system. While non-urgent clinical services have been reduced as far as possible, all kind of specialists turned into COVID-19 specialists. Obstetric assistance cannot be suspended and, at the same time, safety must be guaranteed. In addition, as COVID-19 positive pregnant patients require additional care, some of the clinical habits need to be changed to face emerging needs for a vulnerable but unstoppable kind of patients. We report the management set up in an Obstetrics and Gynecology Unit during the COVID-19 era in a University Hospital in Milan, Italy.", "qid": 23, "docid": "zd3niwqc", "rank": 59, "score": 7.479198932647705}, {"content": "Title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review Content: Objective: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. Data sources: Google Scholar, PubMed, COVID-19 Open Research Dataset: a resource of over 128,000 scholarly articles, including over 59,000 articles with full text related to COVID-19, SARS-CoV-2, and coronaviruses. Methods: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. The search engine was built using a retrieval function that ranks a set of documents based on the query terms appearing in each document regardless of their proximity within the document. Filtering of the articles was then undertaken using keywords and questions, e.g. \"Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?\". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. Findings: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Such reports could lead many oncologists and physicians to change their treatment strategies without solid evidence and recommendations. Further research regarding this relationship and its clinical management is warranted. Additionally, treatment options must be examined further to provide optimal treatment and ensure better outcomes for patients suffering from these comorbidities. It should be noted that, whether definitive measurements exist or not, the care of patients as well as the research involved should be largely prioritized to tackle this deadly pandemic.", "qid": 23, "docid": "kc8xff5n", "rank": 60, "score": 7.463200092315674}, {"content": "Title: Decreased Mortality of COVID-19 with Renin-Angiotensin-Aldosterone System Inhibitors Therapy in Patients with Hypertension: A Meta-Analysis. Content: The coronavirus disease 2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having gradually developed into a pandemic and endangered global health. The continued use of angiotensin converting enzyme inhibitor (ACEIs) and angiotensin II receptor blockers (ARBs) which are part of renin-angiotensin-aldosterone system (RAAS) inhibitors in COVID-19 patients with hypertension has become controversial. We conducted a meta-analysis by searching Pubmed, Web of Science, Scopus and Embase up to 13 May 2020. Data analyses were performed by the Cochrane Collaboration's Review Manager 5.3 software. Finally, we included 9 studies comprising 3936 patients with hypertension and COVID-19 infection. Compared with non-ACEI/ARB treatment, ACEI/ARB treatment was not associated with disease severity (OR 0.71, 95 % CI 0.46-1.08, P 0.11, I2 59%) but was related to lower mortality of COVID-19 in patients with hypertension (OR 0.57, 95 % CI 0.38-0.84, P 0.004, I2 0). In summary, ACEI/ARB therapy did not aggravate disease severity of COVID-19. Besides, ACEI/ARB therapy can decrease the mortality of COVID-19. Current evidence suggested that RAAS inhibitors should be continued in COVID-19 patients with hypertension. Future well-designed randomized controlled trials are needed to confirm these findings.", "qid": 23, "docid": "pknvtj3q", "rank": 61, "score": 7.449900150299072}, {"content": "Title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review Content: BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. \u201cEffects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?\u201c. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.", "qid": 23, "docid": "ab5tgbvm", "rank": 62, "score": 7.436500072479248}, {"content": "Title: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy Content: BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (\u2265 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged \u2265 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (\u2265 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 \u00b1 1.9 vs. 2.5 \u00b1 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (\u2265 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (\u2265 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.", "qid": 23, "docid": "yawjdt5h", "rank": 63, "score": 7.433499813079834}, {"content": "Title: How scientific research reacts to international public health emergencies: a global analysis of response patterns Content: As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.", "qid": 23, "docid": "h4vigeuy", "rank": 64, "score": 7.426599979400635}, {"content": "Title: Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: \u00bfAumentan el riesgo de padecer COVID-19? Content: Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "qid": 23, "docid": "ynias4ga", "rank": 65, "score": 7.398200035095215}, {"content": "Title: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? Content: INTRODUCTION The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.", "qid": 23, "docid": "9o4fymyg", "rank": 66, "score": 7.3979997634887695}, {"content": "Title: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? Content: INTRODUCTION: The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD: In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS: In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION: The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.", "qid": 23, "docid": "o2zoy270", "rank": 67, "score": 7.397998809814453}, {"content": "Title: Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 23, "docid": "fskfnmig", "rank": 68, "score": 7.357900142669678}, {"content": "Title: Renin\u2013Angiotensin\u2013Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin\u2013angiotensin\u2013aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 23, "docid": "oapjfamm", "rank": 69, "score": 7.357899188995361}, {"content": "Title: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy Content: BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (&#8805; 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged &#8805; 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (&#8805; 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 \u00b1 1.9 vs. 2.5 \u00b1 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (&#8805; 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (&#8805; 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.", "qid": 23, "docid": "zl2ohake", "rank": 70, "score": 7.331900119781494}, {"content": "Title: Distribution of Patients at Risk for Complications Related to COVID-19 in the United States: Model Development Study Content: BACKGROUND: Coronavirus disease (COVID-19) has spread exponentially across the United States. Older adults with underlying health conditions are at an especially high risk of developing life-threatening complications if infected. Most intensive care unit (ICU) admissions and non-ICU hospitalizations have been among patients with at least one underlying health condition. OBJECTIVE: The aim of this study was to develop a model to estimate the risk status of the patients of a nationwide pharmacy chain in the United States, and to identify the geographic distribution of patients who have the highest risk of severe COVID-19 complications. METHODS: A risk model was developed using a training test split approach to identify patients who are at high risk of developing serious complications from COVID-19. Adult patients (aged \u226518 years) were identified from the Walgreens pharmacy electronic data warehouse. Patients were considered eligible to contribute data to the model if they had at least one prescription filled at a Walgreens location between October 27, 2019, and March 25, 2020. Risk parameters included age, whether the patient is being treated for a serious or chronic condition, and urban density classification. Parameters were differentially weighted based on their association with severe complications, as reported in earlier cases. An at-risk rate per 1000 people was calculated at the county level, and ArcMap was used to depict the rate of patients at high risk for severe complications from COVID-19. Real-time COVID-19 cases captured by the Johns Hopkins University Center for Systems Science and Engineering (CSSE) were layered in the risk map to show where cases exist relative to the high-risk populations. RESULTS: Of the 30,100,826 adults included in this study, the average age is 50 years, 15% have at least one specialty medication, and the average patient has 2 to 3 comorbidities. Nearly 28% of patients have the greatest risk score, and an additional 34.64% of patients are considered high-risk, with scores ranging from 8 to 10. Age accounts for 53% of a patient\u2019s total risk, followed by the number of comorbidities (29%); inferred chronic obstructive pulmonary disease, hypertension, or diabetes (15%); and urban density classification (5%). CONCLUSIONS: This risk model utilizes data from approximately 10% of the US population. Currently, this is the most comprehensive US model to estimate and depict the county-level prognosis of COVID-19 infection. This study shows that there are counties across the United States whose residents are at high risk of developing severe complications from COVID-19. Our county-level risk estimates may be used alongside other data sets to improve the accuracy of anticipated health care resource needs. The interactive map can also aid in proactive planning and preparations among employers that are deemed critical, such as pharmacies and grocery stores, to prevent the spread of COVID-19 within their facilities.", "qid": 23, "docid": "ayi1m7rk", "rank": 71, "score": 7.323299884796143}, {"content": "Title: Distribution of Patients at Risk for Complications Related to COVID-19 in the United States: Model Development Study Content: BACKGROUND: Coronavirus disease (COVID-19) has spread exponentially across the United States. Older adults with underlying health conditions are at an especially high risk of developing life-threatening complications if infected. Most intensive care unit (ICU) admissions and non-ICU hospitalizations have been among patients with at least one underlying health condition. OBJECTIVE: The aim of this study was to develop a model to estimate the risk status of the patients of a nationwide pharmacy chain in the United States, and to identify the geographic distribution of patients who have the highest risk of severe COVID-19 complications. METHODS: A risk model was developed using a training test split approach to identify patients who are at high risk of developing serious complications from COVID-19. Adult patients (aged &#8805;18 years) were identified from the Walgreens pharmacy electronic data warehouse. Patients were considered eligible to contribute data to the model if they had at least one prescription filled at a Walgreens location between October 27, 2019, and March 25, 2020. Risk parameters included age, whether the patient is being treated for a serious or chronic condition, and urban density classification. Parameters were differentially weighted based on their association with severe complications, as reported in earlier cases. An at-risk rate per 1000 people was calculated at the county level, and ArcMap was used to depict the rate of patients at high risk for severe complications from COVID-19. Real-time COVID-19 cases captured by the Johns Hopkins University Center for Systems Science and Engineering (CSSE) were layered in the risk map to show where cases exist relative to the high-risk populations. RESULTS: Of the 30,100,826 adults included in this study, the average age is 50 years, 15% have at least one specialty medication, and the average patient has 2 to 3 comorbidities. Nearly 28% of patients have the greatest risk score, and an additional 34.64% of patients are considered high-risk, with scores ranging from 8 to 10. Age accounts for 53% of a patient's total risk, followed by the number of comorbidities (29%); inferred chronic obstructive pulmonary disease, hypertension, or diabetes (15%); and urban density classification (5%). CONCLUSIONS: This risk model utilizes data from approximately 10% of the US population. Currently, this is the most comprehensive US model to estimate and depict the county-level prognosis of COVID-19 infection. This study shows that there are counties across the United States whose residents are at high risk of developing severe complications from COVID-19. Our county-level risk estimates may be used alongside other data sets to improve the accuracy of anticipated health care resource needs. The interactive map can also aid in proactive planning and preparations among employers that are deemed critical, such as pharmacies and grocery stores, to prevent the spread of COVID-19 within their facilities.", "qid": 23, "docid": "b72m9x9j", "rank": 72, "score": 7.323298931121826}, {"content": "Title: A Fatal Case of Coronavirus Disease 2019 (COVID-19) in a Patient With Idiopathic Pulmonary Fibrosis Content: The number of cases of coronavirus disease 2019 (COVID-19) has been exponentially increasing everyday. It is important to recognize the comorbidities and risk factors associated with this highly contagious and serious disease that has caused thousands of deaths worldwide. Patients with certain conditions like diabetes, hypertension, cardiovascular disease and chronic lung diseases have been reported to develop serious complications from COVID-19. Idiopathic pulmonary fibrosis (IPF) is a disease that is more prevalent in the elderly population, the same group that are more susceptible to serious complications from COVID-19. Our literature search did not reveal any review about COVID-19 in IPF patients. We report a patient with IPF who was exposed to COVID-19 from her spouse and died from its complications. This case would help to raise the awareness among IPF patients to follow the necessary precautions to reduce the risk of contracting the disease.", "qid": 23, "docid": "a36pn7rz", "rank": 73, "score": 7.274099826812744}, {"content": "Title: [Logistic regression analysis of death risk factors of patients with severe and critical coronavirus disease 2019 and their predictive value]. Content: OBJECTIVE To analyze the risk factors of death in patients with severe and critical coronavirus disease 2019 (COVID-19) and their predictive value. METHODS Using the clinical and epidemiological database of Yangtze River Shipping General Hospital in Wuhan, the clinical and epidemiological data of 105 patients with severe and critical COVID-19 from January to March in 2020 were collected. Multivariate unconditional Logistic regression method was used to analyze the death risk factors of patients during hospitalization. The receiver operating characteristic (ROC) curve was drawn according to the multivariate analysis results to construct a death prediction model; the prediction value of the model was analyzed. RESULTS The 105 patients with severe and critical COVID-19 were enrolled with 66 males (62.9%) and 39 females (37.1%). The age was (58.2\u00b114.4) years old. Forty-two patients died in hospital and 63 survived. Among the dead patients, 69.0% (29/42) were male, and 78.6% (33/42) were over 60 years old. Compared with survival patients, the non-survival patients were older (years old: 59.2\u00b112.5 vs. 51.2\u00b111.4), and had more comorbidities, including coronary heart disease, hypertension, myocardial damage and thrombocytopenia (coronary heart disease: 33.3% vs. 11.1%, hypertension: 28.6% vs. 9.5%, myocardial damage: 73.8% vs. 11.1%, thrombocytopenia: 61.9% vs. 14.3%), and received more mechanical ventilation (92.9% vs. 44.4%), with significant differences (all P < 0.01). The variables of gender, age, basic diseases, mechanical ventilation and complications were included in the unconditional Logistic regression analysis, which showed that gender [odds ratio (OR) = 2.852, 95% confidence interval (95%CI) was 0.122-66.694], age (OR = 3.257, 95%CI was 0.466-18.584), coronary heart disease (OR = 7.337, 95%CI was 0.227-87.021), hypertension (OR = 5.517, 95%CI was 0.258-65.024) and concurrent myocardial damage (OR = 7.322, 95%CI was 0.278-95.020) and thrombocytopenia (OR = 3.968, 95%CI was 0.325-35.549) were independent risk factors for death in patients with severe and critical COVID-19 during hospitalization. According to the risk factors, the death prediction model was constructed and ROC curve was analyzed, which showed that the area under ROC curve (AUC) of death prediction model for predicting the mortality of patients with severe and critical COVID-19 during hospitalization was 0.804, the sensitivity was 83.8%, and the specificity was 82.3%. CONCLUSIONS Various risk factors are associated with the death of severe or critical COVID-19 patients, such as gender, age, basic diseases and complications. The death prediction model is constructed by gender, age, basic diseases with coronary heart disease and hypertension, concurrent myocardial damage and thrombocytopenia, which has certain predictive value for the death of patients with severe or critical COVID-19.", "qid": 23, "docid": "rxpdo0q1", "rank": 74, "score": 7.269800186157227}, {"content": "Title: [Logistic regression analysis of death risk factors of patients with severe and critical coronavirus disease 2019 and their predictive value] Content: OBJECTIVE: To analyze the risk factors of death in patients with severe and critical coronavirus disease 2019 (COVID-19) and their predictive value. METHODS: Using the clinical and epidemiological database of Yangtze River Shipping General Hospital in Wuhan, the clinical and epidemiological data of 105 patients with severe and critical COVID-19 from January to March in 2020 were collected. Multivariate unconditional Logistic regression method was used to analyze the death risk factors of patients during hospitalization. The receiver operating characteristic (ROC) curve was drawn according to the multivariate analysis results to construct a death prediction model; the prediction value of the model was analyzed. RESULTS: The 105 patients with severe and critical COVID-19 were enrolled with 66 males (62.9%) and 39 females (37.1%). The age was (58.2\u00b114.4) years old. Forty-two patients died in hospital and 63 survived. Among the dead patients, 69.0% (29/42) were male, and 78.6% (33/42) were over 60 years old. Compared with survival patients, the non-survival patients were older (years old: 59.2\u00b112.5 vs. 51.2\u00b111.4), and had more comorbidities, including coronary heart disease, hypertension, myocardial damage and thrombocytopenia (coronary heart disease: 33.3% vs. 11.1%, hypertension: 28.6% vs. 9.5%, myocardial damage: 73.8% vs. 11.1%, thrombocytopenia: 61.9% vs. 14.3%), and received more mechanical ventilation (92.9% vs. 44.4%), with significant differences (all P < 0.01). The variables of gender, age, basic diseases, mechanical ventilation and complications were included in the unconditional Logistic regression analysis, which showed that gender [odds ratio (OR) = 2.852, 95% confidence interval (95%CI) was 0.122-66.694], age (OR = 3.257, 95%CI was 0.466-18.584), coronary heart disease (OR = 7.337, 95%CI was 0.227-87.021), hypertension (OR = 5.517, 95%CI was 0.258-65.024) and concurrent myocardial damage (OR = 7.322, 95%CI was 0.278-95.020) and thrombocytopenia (OR = 3.968, 95%CI was 0.325-35.549) were independent risk factors for death in patients with severe and critical COVID-19 during hospitalization. According to the risk factors, the death prediction model was constructed and ROC curve was analyzed, which showed that the area under ROC curve (AUC) of death prediction model for predicting the mortality of patients with severe and critical COVID-19 during hospitalization was 0.804, the sensitivity was 83.8%, and the specificity was 82.3%. CONCLUSIONS: Various risk factors are associated with the death of severe or critical COVID-19 patients, such as gender, age, basic diseases and complications. The death prediction model is constructed by gender, age, basic diseases with coronary heart disease and hypertension, concurrent myocardial damage and thrombocytopenia, which has certain predictive value for the death of patients with severe or critical COVID-19.", "qid": 23, "docid": "w3ep1ubr", "rank": 75, "score": 7.26979923248291}, {"content": "Title: Distribution of ACE2, CD147, CD26 and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors Content: BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2- and CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID-19 morbidity and severity patterns.", "qid": 23, "docid": "8gs2spvy", "rank": 76, "score": 7.250400066375732}, {"content": "Title: Distribution of ACE2, CD147, CD26 and other SARS\u2010CoV\u20102 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID\u201019 risk factors Content: BACKGROUND: Morbidity and mortality from COVID\u201019 caused by novel coronavirus SARS\u2010CoV\u20102 is accelerating worldwide and novel clinical presentations of COVID\u201019 are often reported. The range of human cells and tissues targeted by SARS\u2010CoV\u20102, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS\u2010CoV\u20102 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID\u201019. METHODS: We performed RNA sequencing and explored available RNA\u2010Seq databases to study gene expression and co\u2010expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4(+) and CD8(+) T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID\u201019 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age\u2010related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2\u2010 and CD147\u2010related genes in the bronchial biopsy, BAL or blood. Additionally, CD147\u2010related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2\u2010 and CD147\u2010related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS\u2010CoV\u20102 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID\u201019 morbidity and severity patterns.", "qid": 23, "docid": "fwu28811", "rank": 77, "score": 7.250399112701416}, {"content": "Title: Obesity and Higher Risk for Severe Complications of Covid-19: What to do when the two pandemics meet Content: The coronavirus disease 2019 (COVID-19) pandemic has spread around the globe, infecting more than ten million individuals, with more than 500,000 dead; about one half of the infected people have recovered. Despite this fact, a subgroup of individuals affected by COVID-19 is at greater risk of developing worse outcomes and experience a high rate of mortality. Data on the association between obesity and COVID-19 are growing; the available studies, have reported a high prevalence of overweight and obesity in patients experiencing a severe COVID-19 course, with serious complications requiring hospitalization and admission to intensive care units. This paper attempts to highlight potential mechanisms behind the greater vulnerability to COVID-19 of individuals with obesity. The presence of uncontrolled chronic obesity-related comorbidities, particularly pulmonary diseases, can present a primary fertile soil for respiratory tract infection. Combined with immune system impairments, such as alteration in the T-cell proliferation and macrophage differentiation, and the high pro-inflammatory cytokine production by the adipose organ, this may worsen the general condition toward a systemic diffusion of infection. Prevention remains the first line of intervention in these patients that can be achieved by adhering to social distancing and adopting hygiene precautions, combined with a healthy lifestyle. Patients with obesity require preferential access dedicated to primary care services to ensure they are regularly taking their medications for the treatment of any concurrent chronic diseases. Finally, their physicians must promptly manage any medical signs or symptoms in the case of suspected severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection to prevent the risk of severe outcomes.", "qid": 23, "docid": "q784lpo9", "rank": 78, "score": 7.220699787139893}, {"content": "Title: Obesity and Higher Risk for Severe Complications of Covid-19: What to do when the two pandemics meet. Content: The coronavirus disease 2019 (COVID-19) pandemic has spread around the globe, infecting more than ten million individuals, with more than 500,000 dead; about one half of the infected people have recovered. Despite this fact, a subgroup of individuals affected by COVID-19 is at greater risk of developing worse outcomes and experience a high rate of mortality. Data on the association between obesity and COVID-19 are growing; the available studies, have reported a high prevalence of overweight and obesity in patients experiencing a severe COVID-19 course, with serious complications requiring hospitalization and admission to intensive care units. This paper attempts to highlight potential mechanisms behind the greater vulnerability to COVID-19 of individuals with obesity. The presence of uncontrolled chronic obesity-related comorbidities, particularly pulmonary diseases, can present a primary fertile soil for respiratory tract infection. Combined with immune system impairments, such as alteration in the T-cell proliferation and macrophage differentiation, and the high pro-inflammatory cytokine production by the adipose organ, this may worsen the general condition toward a systemic diffusion of infection. Prevention remains the first line of intervention in these patients that can be achieved by adhering to social distancing and adopting hygiene precautions, combined with a healthy lifestyle. Patients with obesity require preferential access dedicated to primary care services to ensure they are regularly taking their medications for the treatment of any concurrent chronic diseases. Finally, their physicians must promptly manage any medical signs or symptoms in the case of suspected severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection to prevent the risk of severe outcomes.", "qid": 23, "docid": "vyzy6lmg", "rank": 79, "score": 7.220698833465576}, {"content": "Title: Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation. Content: BACKGROUND Renal denervation (RDN) is a catheter-based intervention to treat patients with resistant hypertension. The biological effects of RDN are not fully understood, and randomized controlled trials have generated conflicting evidence. This report presents data from the Swedish Registry for Renal Denervation, an investigator-driven nationwide registry. PURPOSE To assess the safety and efficacy of RDN on patients with resistant hypertension in a real-world clinical setting. METHODS This nationwide database contains patient characteristics, procedural details, and follow-up data on all RDN procedures performed in Sweden. Consecutive procedures between 2011 and 2015 were included. RESULTS The data analysis consists of 252 patients (mean age 61 \u00b1 10 years, 38% women; mean 4.5 \u00b1 1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood pressure (BP) decreased 6 months after RDN (176 \u00b1 23/97 \u00b1 17 to 161 \u00b1 26/91 \u00b1 16 mmHg, both P < 0.001; and 155 \u00b1 17/89 \u00b1 14 to 147 \u00b1 18/82 \u00b1 12 mmHg, both P < 0.001). Significant office and ambulatory BP reductions persisted throughout the observation period of 36 months. Major procedure-related vascular complications occurred in four patients. Renal function and number of antihypertensive drugs were unchanged during follow-up. CONCLUSION In this complete national cohort, RDN was associated with a sustained reduction in office and ambulatory BP in patients with resistant hypertension. The procedure proved to be feasible and associated with a low-complication rate, including long-term adverse events.", "qid": 23, "docid": "tdfrzxz0", "rank": 80, "score": 7.195000171661377}, {"content": "Title: Lessons learnt from COVID 19: An Italian multicentric epidemiological study of orthopaedic and trauma services Content: INTRODUCTION: The Pandemic caused by the SARS-CoV-2 has put a strain on the most of health systems all over the world. Many hospitals had to re-organize to deal with the emergency, so that the non-core activities have been suspended or cancelled, raising management problems. The aim of this multicentre study is to report the epidemiological orthopaedic and traumatological data between COVID and pre-COVID era and to analyse patients\u2019 needs and their management. METHODS: We reported and compared traumatological and elective orthopaedic surgeries performed in three of the main hospital centres in Tuscany during COVID (March 2020) and pre-COVID (March 2019) era. We also reported the epidemiological data about the number of orthopaedic first aid visits at the main hub, analysing the main differences. For each centre, we reported the number, diagnosis, co-morbidities, treatment, hospital course, complications and outcomes of confirmed COVID 19 patients. We also indicated what kind of PPE were used by medical staff and patients at any visit. RESULTS: The scheduled surgery drastically decreased in all the centres and the most of procedures were carried out for tumours, infections and implant mobilizations during the COVID time, delaying all the other ones. Trauma activities slightly decreased between the two time points: proximal femur fractures continued to engage our hospitals at the same pre-COVID volumes, while minor traumas drastically decreased. We report a decrease of 70.95% in orthopaedic first aid, with first-aid-visits/hospitalization ratio of 14.3 in the pre-COVID time vs 6.3 in the COVID time. A total of 5 confirmed COVID patients were treated for fractures and 4 of them healed without complications. We report just one case of death among COVID patients. All the medical staff members have worn the PPE and no one have developed COVID symptoms. CONCLUSIONS: The COVID-19 raised many important issues, such as the optimal management of patients requiring the treatment of conventional diseases during a pandemic. The flow of patients changes from one area to another during a pandemic and an integrated approach within the same geographical area could be useful to better allocate resources and manage the patients\u2019 needs. The preventive measures put in place in our country seem to work, but this first experience with COVID-19 crisis highlighted the chronic problems of our health system and we believe that we have to \u201clearn the lesson\u201d to be better prepared in the future.", "qid": 23, "docid": "j8szwaqj", "rank": 81, "score": 7.156199932098389}, {"content": "Title: Guillain Barr e syndrome in COVID-19:A scoping review Content: Introduction The novel coronavirus (COVID19) can result in several neurological complications. Guillain-Barre Syndrome (GBS) is one of them and has been reported from different parts of the world in this pandemic. It is an acute post-infectious polyneuropathy. The review aims to summarize the demographic features, clinical presentation, diagnostics workup, and management strategies of COVID-19 associated GBS reported in the literature. Material and method We searched Medline, PubMed Central, SCOPUS, and Google Scholar using pre-defined keywords, with no time limits and in the English language only. We aimed to include all kinds of manuscripts. The last search was done on 18th May 2020. Demographics, clinical features, diagnostic workup, management, and outcomes were documented in the datasheet. Results We identified 24 cases of COVID-19 associated GBS. Most of the cases were reported from Italy followed by the USA. The majority were males (18 /24) The age ranged from 23 -84 years. The clinical presentation was typical sensory-motor GBS in most. Nine patients had facial palsy of which five had bilateral involvement. Two patients had bilateral abducent nerve palsy while two presented as paraparetic GBS variant with autonomic dysfunction. Electrodiagnostics was performed in 17 patients only and 12 had typical features of acute inflammatory demyelinating polyneuropathy. Intravenous immunoglobulins were the preferred mode of treatment in most of the patient. There was one death, and most were discharged to rehabilitation or home. Conclusion GBS is a frequent neurological complication associated with COVID-19. There is no clear causative relationship between GBS, and COVID-19 at present, and more data are needed to establish the casualty. However, most cases have a post-infectious onset with male preponderance. Most of the cases have a typical presentation but some may present in an atypical way. Prognosis is generally good.", "qid": 23, "docid": "oc2pb00b", "rank": 82, "score": 7.142399787902832}, {"content": "Title: Mental Health Care Providers Dealing With Coronavirus Disease 2019 (COVID-19): What Is the Definition of a Case, How Is That Changing, and What Kinds of Tests Are Available? Content: The goal of this column is to inform mental health care professionals about the evolving way the diagnosis of Coronavirus Disease 2019 (COVID-19) is being made, with emphasis on tests to assist in making the diagnosis and to determine the presence of antibodies to the virus. This column also provides some general information about the disease, its relative risks, and efforts to develop effective treatments. Links to credible websites that are being continuously updated are also provided for readers who want more information and to stay current with ongoing developments.", "qid": 23, "docid": "b5efo2fm", "rank": 83, "score": 7.140500068664551}, {"content": "Title: Investigation of Turkish dentists' clinical attitudes and behaviors towards the COVID-19 pandemic: a survey study Content: Currently, the whole world is under the threat of the COVID-19 pandemic, and dentists are at high risk. The aim of this study was to investigate what kind of precautions Turkish dentists take in dental clinics during the COVID-19 pandemic. The study population consisted of dentists in Turkey. An online questionnaire (23 questions-57 items) was sent to a sample of Turkish dentists from March 16 to March 20, 2020. The questionnaire comprised a series of questions about dentists' demographic characteristics, their concerns, and the measures taken in dental clinics against COVID-19. This study included a total of 1,958 Turkish dentists. A total of 1,274 (65.1%) were general dentists, and 684 (34.9%) were specialists. Five hundred twenty-two (26.7%) dentists attended an informational meeting on COVID-19. Of these dentists, 69.8% were aware of COVID-19 according to their self-assessed knowledge scores. More than 90% of the dentists were concerned about themselves and their families. Only 12% of the dentists wore an N95 mask. Although Turkish dentists took some precautionary measures, they did not take enough precautions to protect themselves, the dental staff, and other patients from COVID-19. As the number of COVID-19 cases increased, the measures taken slightly increased in dental clinics as well. Dentists are strongly recommended to take maximum precautions in the clinical setting. The guidelines about the COVID-19 pandemic should be sent to all dentists by the regional and national dental associations.", "qid": 23, "docid": "6d25aq3i", "rank": 84, "score": 7.137800216674805}, {"content": "Title: Investigation of Turkish dentists' clinical attitudes and behaviors towards the COVID-19 pandemic: a survey study. Content: Currently, the whole world is under the threat of the COVID-19 pandemic, and dentists are at high risk. The aim of this study was to investigate what kind of precautions Turkish dentists take in dental clinics during the COVID-19 pandemic. The study population consisted of dentists in Turkey. An online questionnaire (23 questions-57 items) was sent to a sample of Turkish dentists from March 16 to March 20, 2020. The questionnaire comprised a series of questions about dentists' demographic characteristics, their concerns, and the measures taken in dental clinics against COVID-19. This study included a total of 1,958 Turkish dentists. A total of 1,274 (65.1%) were general dentists, and 684 (34.9%) were specialists. Five hundred twenty-two (26.7%) dentists attended an informational meeting on COVID-19. Of these dentists, 69.8% were aware of COVID-19 according to their self-assessed knowledge scores. More than 90% of the dentists were concerned about themselves and their families. Only 12% of the dentists wore an N95 mask. Although Turkish dentists took some precautionary measures, they did not take enough precautions to protect themselves, the dental staff, and other patients from COVID-19. As the number of COVID-19 cases increased, the measures taken slightly increased in dental clinics as well. Dentists are strongly recommended to take maximum precautions in the clinical setting. The guidelines about the COVID-19 pandemic should be sent to all dentists by the regional and national dental associations.", "qid": 23, "docid": "crtf3fhk", "rank": 85, "score": 7.137799263000488}, {"content": "Title: Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis Content: Abstract Background Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. Methods Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. Results The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3\u201389.9 %), 65.7 % (95CI 60.1\u201371.4 %), 42.4 % (95CI 32.2\u201352.6 %) and 21.4 % (95CI 15.3\u201327.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1\u20139.3 %), hypertension was 15.6 % (95CI 12.6\u201318.6 %), cardiovascular disease was 4.7 % (95CI 3.1\u20136.2 %), and malignancy was 1.2 % (95CI 0.5\u20131.8 %). The complications, including ARDS risk, ranged from 5.6\u201313.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7\u201310.8 %), AKI at 2.1 % (95CI 0.6\u20133.7 %), and shock at 4.7 % (95CI 0.9\u20138.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0\u201361.9 %) and 41.7 % (95CI 26.4\u201356.9 %), respectively. Conclusion Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.", "qid": 23, "docid": "r4e4tg7r", "rank": 86, "score": 7.128300189971924}, {"content": "Title: Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. METHODS: Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. RESULTS: The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3-89.9 %), 65.7 % (95CI 60.1-71.4 %), 42.4 % (95CI 32.2-52.6 %) and 21.4 % (95CI 15.3-27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1-9.3 %), hypertension was 15.6 % (95CI 12.6-18.6 %), cardiovascular disease was 4.7 % (95CI 3.1-6.2 %), and malignancy was 1.2 % (95CI 0.5-1.8 %). The complications, including ARDS risk, ranged from 5.6-13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7-10.8 %), AKI at 2.1 % (95CI 0.6-3.7 %), and shock at 4.7 % (95CI 0.9-8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0-61.9 %) and 41.7 % (95CI 26.4-56.9 %), respectively. CONCLUSION: Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.", "qid": 23, "docid": "u42iq0jk", "rank": 87, "score": 7.128299236297607}, {"content": "Title: Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. Content: INTRODUCTION As the coronavirus disease 2019 (COVID-19) outbreak, identification of clinical predictors of severe or fatal disease are necessary to enable risk stratification and optimize allocation of limited resources. Hypertension has been widely reported to be associated with increase disease severity, however, other studies have reported different findings. OBJECTIVES To evaluate the association of hypertension and severe and fatal COVID-19. PATIENTS AND METHODS Scopus, Medline, and Web of Science was performed to identify studies reporting the rate of hypertension in COVID-19 patients with severe or non-severe disease or among survivors and non-survivors. The obtained data was pooled into a meta-analysis to calculate odds ratio (OR) with 95% confidence intervals (95%CI). RESULTS Hypertension was associated with a nearly 2.5-fold significantly increased risk of severe COVID-19 disease (OR: 2.49 [95%CI: 1.98-3.12] I2=24%), as well as with a similarly significant higher risk of mortality (OR: 2.42 [95%CI: 1.51-3.90] I2=0%). In meta-regression, a significant correlation was observed with an increase in mean age of patients with severe COVID-19 associated with increased log odds of hypertension and severity (p=0.03). CONCLUSIONS The results of this pooled analysis of the current scientific literature would suggest that hypertension may be associated with an up to 2.5-fold higher risk of severe and fatal COVID-19, especially among older individuals.", "qid": 23, "docid": "komx6t5h", "rank": 88, "score": 7.127900123596191}, {"content": "Title: Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan Content: Abstract Background In December 2019, COVID-19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. Objective The severity on admission, complications, treatment, and outcomes of COVID-19 patients were evaluated. Methods Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. Results We identified 269 (49.1%) of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-a), and high LDH level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in COVID-19 patients was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. Conclusions Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have high risk of death.", "qid": 23, "docid": "0euaaspo", "rank": 89, "score": 7.125500202178955}, {"content": "Title: Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan Content: BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. OBJECTIVE: We sought to evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19. METHODS: Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020, to February 5, 2020, were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. RESULTS: We identified 269 (49.1%) of 548 patients as severe cases on admission. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-&#945;), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. CONCLUSIONS: Patients with older age, hypertension, and high lactate dehydrogenase level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have a high risk of death.", "qid": 23, "docid": "im9v9ezp", "rank": 90, "score": 7.125499248504639}, {"content": "Title: The role of laparoscopic sleeve gastrectomy as a treatment for morbid obesity; review of outcomes. Content: BACKGROUND Global prevalence of obesity has soared. Where lifestyle and medical treatments have failed, laparoscopic sleeve gastrectomy (LSG) is increasingly regarded as a good surgical procedure for morbid obesity. Following the introduction of LSG, we assessed our surgical outcomes. METHODS We reviewed a consecutive series of LSGs from January 2009 to January 2015. Our primary focus was to assess the success of this procedure on the percentage excess body weight loss (%EWL), Body Mass Index (BMI), hypertension and diabetes. Additionally, we evaluated the rate of procedure-related complications. RESULTS There were 183 consecutive patients evaluated. Median age was 45 years (24-73). The majority were female (73.2 %, n = 134). At 1 year post-op, median %EWL was 57.6 %. There was an associated median reduction in BMI of 16 kg/m2 (0-33). At 2 years, median %EWL was sustained at 58.4 %. The median reduction in BMI was 16 kg/m2 (4-32). At 2-year post-op, 78.9 % of diabetic patients had their diabetic medications completely discontinued, while a further 15.8 % having their medication reduced. 34.6 % of hypertensive patients had their antihypertensives discontinued, with 50 % having medications reduced. There was no procedure related mortality. 3.3 % (n = 6) of patients had a confirmed staple-line leak. CONCLUSION This study shows LSG is a safe and successful management strategy for morbid obesity. In addition to the direct effects of sustained weight loss, it highlights indirect effects that LSG has on obesity-related health issues, with substantial reduction in diabetic and anti-hypertensive medications. Our results reaffirm international studies of the beneficial effects of LSG on Type II diabetes and hypertension.", "qid": 23, "docid": "2byzoaa7", "rank": 91, "score": 7.120500087738037}, {"content": "Title: COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. Content: The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1-9 and Ang 1-7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.", "qid": 23, "docid": "ln9cv9zb", "rank": 92, "score": 7.109899997711182}, {"content": "Title: Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin\u2013angiotensin system inhibitors Content: In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25\u201386 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 \u00d7 10(9)/L vs 1.26 \u00d7 10(9)/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "qid": 23, "docid": "d4mf43j9", "rank": 93, "score": 7.089099884033203}, {"content": "Title: Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin-angiotensin system inhibitors Content: In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25-86 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 \u00d7 109/L vs 1.26 \u00d7 109/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "qid": 23, "docid": "faz8uw2d", "rank": 94, "score": 7.089098930358887}, {"content": "Title: On mothering and being mothered: a personal reflection on women's productivity during Covid\u201019 Content: This is a personal reflection, as a female academic during Covid\u201019, on how women's academic productivity seems primarily to be discussed in relation to a different kind of productivity\u2013motherhood. A recent procedure in a maternity hospital, evoked feelings and associations of mothering and being mothered, and how these associations hover over relationships regardless of whether wombs are productive or not. My hope in writing this piece, is that every woman's fear and anxiety may be productively contained (regardless of how she is seen from the outside or momentarily construed from within) during this time of extraordinary turmoil.", "qid": 23, "docid": "jbuy5jjw", "rank": 95, "score": 7.088099956512451}, {"content": "Title: Familial hypercholesterolemia and COVID-19: triggering of increased sustained cardiovascular risk. Content: Early data from Wuhan, China show that patients with COVID-19 are typically male, aged 40 to 60 years, and about one-third have comorbidities. Moreover, of 138 COVID-19 patients hospitalized in Wuhan and treated in an intensive care unit (ICU), 25% had cardiovascular disease and 58% hypertension; the respective figures for non-ICU-treated COVID-19 patients were 10% and 22% [1]. Based on these early data, a predisposition to acute cardiac complications related to underlying atherosclerotic cardiovascular disease (ASCVD) may significantly increase the severity of COVID-19 in susceptible individuals.", "qid": 23, "docid": "io8hm94a", "rank": 96, "score": 7.086599826812744}, {"content": "Title: COVID-19 pandemic in Panama: lessons of the unique risks and research opportunities for Latin America Content: The Republic of Panama has the second most unequally distributed wealth in Central America, has recently entered the list of countries affected by the COVID-19 pandemic, and has one of the largest testing rate per inhabitant in the region and consequently the highest incidence rate of COVID-19, making it an ideal location to discuss potential scenarios for assessing epidemic preparedness, and to outline research opportunities in the Region of the Americas. We address two timely important questions: What are the unique risks of COVID-19 in Panama that could help other countries in the Region be better prepared? And what kind of scientific knowledge can Panama contribute to the regional and global study of COVID-19? This paper provides suggestions about how the research community could support local health authorities plan for different scenarios and decrease public anxiety. It also presents basic scientific opportunities about emerging pandemic pathogens towards promoting global health from the perspective of a middle income country.", "qid": 23, "docid": "x16659y5", "rank": 97, "score": 7.083199977874756}, {"content": "Title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature Content: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.", "qid": 23, "docid": "ntv2g7ne", "rank": 98, "score": 7.079400062561035}, {"content": "Title: Is periodontal disease a risk factor for severe COVID-19 illness? Content: Periodontal disease (PD) comprises a group of diseases involving inflammatory aspects of the host and dysbiotic events that affect periodontal tissues and could have systemic implications. Diverse factors and comorbidities have been closely associated with PD such as diabetes, obesity, aging, hypertension, and so on; although, underlying mechanisms or causal associations have not been established completely. Interestingly, these same factors have been widely associated with progression or severe coronavirus disease 2019 (COVID-19), an illness caused by coronavirus SARS-CoV-2. Since inflammatory and dysbiotic factors as well as comorbidities affect systemic health, it is possible that periodontal status indicates the risk of complication of COVID-19. However, assessment of oral health history including periodontal status in COVID-19 patients has not been reported. Knowing PD is associated with severe COVID-19 could help identify risk groups and establish pertinent recommendations.", "qid": 23, "docid": "rcps7u8h", "rank": 99, "score": 7.07289981842041}, {"content": "Title: Is periodontal disease a risk factor for severe COVID-19 illness? Content: Periodontal disease (PD) comprises a group of diseases involving inflammatory aspects of the host and dysbiotic events that affect periodontal tissues and could have systemic implications. Diverse factors and comorbidities have been closely associated with PD such as diabetes, obesity, aging, hypertension, and so on; although, underlying mechanisms or causal associations have not established completely. Interestingly, these same factors have widely associated with progression or severe coronavirus disease 2019 (COVID-19), an illness caused by coronavirus named SARS-CoV-2. Since inflammatory and dysbiotic factors as well as comorbidities affect systemic health, it is possible that periodontal status indicates the risk of complication of COVID-19. However, assessment of oral health history including periodontal status in COVID-19 patients has not been reported. Knowing PD is associated with severe COVID-19 could help identify risk groups and establish pertinent recommendations.", "qid": 23, "docid": "wmskc7z5", "rank": 100, "score": 7.072898864746094}]}
{"query": "what kinds of complications related to COVID-19 are associated with diabetes", "hits": [{"content": "Title: Diabetes and COVID\u201019: psychosocial consequences of the COVID\u201019 pandemic in people with diabetes in Denmark\u2014what characterizes people with high levels of COVID\u201019\u2010related worries? Content: AIM: To map COVID\u201019\u2010specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID\u201019 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID\u201019 pandemic. METHODS: A cross\u2010sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID\u201019\u2010specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes\u2010specific social support, diabetes distress and changes in diabetes\u2010specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID\u201019\u2010specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID\u201019, about one\u2010third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID\u201019 and diabetes. CONCLUSION: People with diabetes have COVID\u201019\u2010specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID\u201019 and diabetes.", "qid": 24, "docid": "3jolt83r", "rank": 1, "score": 11.774100303649902}, {"content": "Title: Diabetes and COVID-19: psychosocial consequences of the COVID-19 pandemic in people with diabetes in Denmark-what characterizes people with high levels of COVID-19-related worries? Content: AIM: To map COVID-19-specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID-19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID-19-specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes-specific social support, diabetes distress and changes in diabetes-specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID-19-specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID-19, about one-third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID-19 and diabetes. CONCLUSION: People with diabetes have COVID-19-specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID-19 and diabetes.", "qid": 24, "docid": "hycd9zua", "rank": 2, "score": 11.774099349975586}, {"content": "Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "qid": 24, "docid": "5zb96j4a", "rank": 3, "score": 10.531000137329102}, {"content": "Title: Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis Content: Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.", "qid": 24, "docid": "tsd6sjcx", "rank": 4, "score": 9.992600440979004}, {"content": "Title: Predicting mortality attributable to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico Content: BACKGROUND AND AIMS: The SARS-CoV-2 outbreak has posed a challenge to the healthcare systems due to high complications rates observed in patients with cardiometabolic diseases, such as diabetes and obesity. Despite the high prevalence of these conditions, a mechanistic association of its interactions in COVID-19 remain unclear. Here, we identify risk factors and propose a clinical score to predict 30-day lethality in COVID-19 cases, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of suspected, confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to SARS-CoV-2 positivity and mortality due to COVID-19. Additionally, we explored the impact of diabetes and obesity on COVID-19 related outcomes and their interaction with other comorbidities in modifying COVID-19 related lethality. Finally, we built our clinical score to predict 30-day lethality using the previously identified risk factors. RESULTS: Among 49,570 evaluated subjects (at April 19th, 2020), we observed an increased risk of SARS-CoV-2 positivity (n=8,261) in those with diabetes, obesity, male subjects and in patients with diabetes and age <40 years (early-onset). Risk factors for increased lethality in COVID-19 includes early-onset diabetes obesity, chronic obstructive pulmonary disease, advanced age, immunosuppression, and chronic kidney disease; we also found that obesity mediates 47.8% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age [\u2265]65 years, diabetes, diabetes & age <40 years, obesity, age <40 years, CKD, pregnancy and immunosuppression and a categorization of low-risk, mild-risk, moderate-risk, high-risk and very high-risk significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.837). CONCLUSIONS: Here, we propose a mechanistic approach to evaluate risk for complication and lethality attributable to COVID-19 in patients with obesity and diabetes patients in a country with high susceptibility. Furthermore, our novel score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.", "qid": 24, "docid": "bvksvy6u", "rank": 5, "score": 9.737199783325195}, {"content": "Title: Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico Content: BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among 177,133 subjects at May 18(th), 2020, we observed 51,633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, COPD, advanced age, hypertension, immunosuppression, and CKD; we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age \u226565 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.823). RESULTS: Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.", "qid": 24, "docid": "xrmwpep6", "rank": 6, "score": 9.42710018157959}, {"content": "Title: Predicting Mortality Due to SARS-CoV-2: A Mechanistic Score Relating Obesity and Diabetes to COVID-19 Outcomes in Mexico Content: BACKGROUND: The SARS-CoV-2 outbreak poses a challenge to health care systems due to its high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity, and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of the Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19-related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among the 177\u00e2\u0080 133 subjects at the time of writing this report (May 18, 2020), we observed 51\u00e2\u0080 633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, chronic obstructive pulmonary disease, advanced age, hypertension, immunosuppression, and chronic kidney disease (CKD); we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for intensive care unit admission and intubation. Our predictive score for COVID-19 lethality included age\u00e2\u0080 &#8805;\u00e2\u0080 65 years, diabetes, early-onset diabetes, obesity, age\u00e2\u0080 <\u00e2\u0080 40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (C-statistic\u00e2\u0080 =\u00e2\u0080 0.823). CONCLUSIONS: Here, we propose a mechanistic approach to evaluate the risk for complications and lethality attributable to COVID-19, considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first-contact scenario.", "qid": 24, "docid": "ezny6ajo", "rank": 7, "score": 9.340100288391113}, {"content": "Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords \u201cCOVID-19\u201d and \u201cDiabetes\u201d was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute \u03b2-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "qid": 24, "docid": "phf2sgw5", "rank": 8, "score": 9.058199882507324}, {"content": "Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords \"COVID-19\" and \"Diabetes\" was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute \u00df-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "qid": 24, "docid": "wl1uihn3", "rank": 9, "score": 9.058198928833008}, {"content": "Title: Sex-gender-related therapeutic approaches for cardiovascular complications associated with diabetes. Content: Diabetes is a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease. Cardiovascular complications associated with diabetes are among the most important causes of death in diabetic patients. Interestingly, several sex-gender differences have been reported to significantly impact in the pathophysiology of diabetes. In particular, sex-gender differences have been reported to affect diabetes epidemiology, risk factors, as well as cardiovascular complications associated with diabetes. This suggests that different therapeutic approaches are needed for managing diabetes-associated cardiovascular complications in men and women. In this review, we will discuss about the sex-gender differences that are known to impact on diabetes, mainly focusing on the cardiovascular complications associated with the disease. We will then discuss the therapeutic approaches for managing diabetes-associated cardiovascular complications and how differences in sex-gender can influence the existing therapeutic approaches.", "qid": 24, "docid": "cctvpphp", "rank": 10, "score": 8.955400466918945}, {"content": "Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "qid": 24, "docid": "bjq36px5", "rank": 11, "score": 8.902299880981445}, {"content": "Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "qid": 24, "docid": "yjugtbg1", "rank": 12, "score": 8.902298927307129}, {"content": "Title: Personal Experience With COVID-19 and Diabetes in the South of France: Technology Facilitates the Management of Diabetes in Disruptive Times. Content: We report our experience with COVID-19 epidemic in patients with type 1 diabetes using diabetes technology in the South of France. Use of insulin pumps and continuous glucose monitoring appeared as an effective way to prevent the risk of acute metabolic complications related to the changes of daily life associated with requested confinement . Care by telemedicine was facilitated in these patients who used diabetes technology while structured education delivered during training and support from home care services were helpful to master the disruptive conditions.", "qid": 24, "docid": "kzoumf3k", "rank": 13, "score": 8.897600173950195}, {"content": "Title: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature Content: The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes.", "qid": 24, "docid": "e5mf6qdo", "rank": 14, "score": 8.854000091552734}, {"content": "Title: Can pioglitazone be potentially useful therapeutically in treating patients with covid-19? Content: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPAR\u03b3 agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.", "qid": 24, "docid": "9qpe4qm4", "rank": 15, "score": 8.79319953918457}, {"content": "Title: Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPAR\u00ce\u00b3 agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.", "qid": 24, "docid": "weyym7tx", "rank": 16, "score": 8.793198585510254}, {"content": "Title: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature Content: The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05164-x) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.", "qid": 24, "docid": "15hqzcig", "rank": 17, "score": 8.780900001525879}, {"content": "Title: Health Sensors, Smart Home Devices, and the Internet of Medical Things: An Opportunity for Dramatic Improvement in Care for the Lower Extremity Complications of Diabetes. Content: OBJECTIVE The prevalent and long-neglected diabetic foot ulcer (DFU) and its related complications rank among the most debilitating and costly sequelae of diabetes. With the rise of the Internet of medical things (IoMT), along with smart devices, the med-tech industry is on the cusp of a home-care revolution, which could also create opportunity for developing effective solutions with significant potential to reduce DFU-associated costs and saving limbs. This article discusses potential applications of IoMT to the DFU patient population and beyond. METHODS To better understand potential opportunities and challenges associated with implementing IoMT for management of DFU, the authors reviewed recent relevant literatures and included their own expert opinions from a multidisciplinary point of view including podiatry, engineering, and data security. RESULTS The IoMT has opened digital transformation of home-based diabetic foot care, as it enables promoting patient engagement, personalized care and smart management of chronic and noncommunicable diseases through individual data-driven treatment regimens, telecommunication, data mining, and comprehensive feedback tailored to individual requirements. In particular, with recent advances in voice-activated commands technology and its integration as a part of IoMT, new opportunities have emerged to improve the patient's central role and responsibility in enabling an optimized health care ecosystem. CONCLUSIONS The IoMT has opened new opportunities in health care from remote monitoring to smart sensors and medical device integration. While it is at its early stage of development, ultimately we envisage a connected home that, using voice-controlled technology and Bluetooth-radio-connected add-ons, may augment much of what home health does today.", "qid": 24, "docid": "d33i6iio", "rank": 18, "score": 8.768500328063965}, {"content": "Title: Diabetes and COVID-19: IDF perspective in the Western Pacific Region Content: Abstract The World Health Organization (WHO) declared a pandemic, the highest risk level in the infectious disease alert phase, on 11 March 2020. In the Western Pacific Region (WPR), 192,016 confirmed cases with 7,125 deaths had been reported as of 8 June 2020. In people with diabetes COVID-19 can be more difficult to treat due to the wide fluctuations in blood glucose levels or presence of comorbidities such as diabetes complications, including cardiovascular disease and renal damage, which are recognized risks for adverse outcomes. National diabetes associations and governments have established guidelines for subjects with diabetes in relation to COVID-19, and are trying to supply emergency and their regularly required medical products for them. The WPR is so large and composed of such diverse countries and COVID-19 situations, no one conclusion or program applies. Instead we could see a diverse COVID-19 pandemic profile in the WPR, and several creative diagnostic and therapeutic measures undertaken. This includes drive-through screening facilities, high-speed RT-PCR technologies, convalescent patients\u2019 plasma therapy, which potentially had some positive contributions in combatting COVID-19 in the WPR as well as globally. Although the numbers of confirmed cases are currently decreasing in the region, the COVID-19 pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of COVID-19.", "qid": 24, "docid": "fhkbcp7z", "rank": 19, "score": 8.650300025939941}, {"content": "Title: Diabetes and COVID-19: IDF perspective in the Western Pacific region Content: The World Health Organization (WHO) declared a pandemic, the highest risk level in the infectious disease alert phase, on 11 March 2020. In the Western Pacific Region (WPR), 192,016 confirmed cases with 7125 deaths had been reported as of 8 June 2020. In people with diabetes COVID-19 can be more difficult to treat due to the wide fluctuations in blood glucose levels or presence of comorbidities such as diabetes complications, including cardiovascular disease and renal damage, which are recognized risks for adverse outcomes. National diabetes associations and governments have established guidelines for subjects with diabetes in relation to COVID-19, and are trying to supply emergency and their regularly required medical products for them. The WPR is so large and composed of such diverse countries and COVID-19 situations, no one conclusion or program applies. Instead we could see a diverse COVID-19 pandemic profile in the WPR, and several creative diagnostic and therapeutic measures undertaken. This includes drive-through screening facilities, high-speed RT-PCR technologies, convalescent patients' plasma therapy, which potentially had some positive contributions in combatting COVID-19 in the WPR as well as globally. Although the numbers of confirmed cases are currently decreasing in the region, the COVID-19 pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of COVID-19.", "qid": 24, "docid": "kfyvzjiq", "rank": 20, "score": 8.650299072265625}, {"content": "Title: Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India Content: BACKGROUND AND AIMS: During the current pandemic of COVID-19 India is under lockdown which could cause disruption in diet and lifestyle in patients with type 2 diabetes (T2DM). We aimed to study lifestyle changes and other common issues related to treatment in our previously seen and treated patients with T2DM. METHODS: Patients (n, 150) who were regularly following up before lockdown were interviewed telephonically (after 45 days of start of lockdown) regarding lifestyle changes, stress and other diabetes-related questions. RESULT: Carbohydrate consumption and frequency of snacking increased in 21% and 23% patients, respectively. Interestingly, 27% patients reported an increase in consumption of fruits. Exercise duration was reduced in 42% and weight gain occurred in 19% patients. Frequency of doing self-monitoring of blood glucose (SMBG) was decreased in 23% patients. \u2018Mental stress\u2019 of any kind was reported in 87% patients. Availability of medicine and insulin was uninterrupted in 91% patients. Knowledge about telemedicine was present in 69% and majority (92%) of these patients preferred video consultation. CONCLUSION: During 45 days of lockdown increase in carbohydrate intake, decrease in exercise, decreased SMBG and widespread mental stress in patients with T2DM was seen, factors which may destabilize or exacerbate hyperglycemia and hypertension. Some positive changes (e.g. increased intake of fruits) were also observed.", "qid": 24, "docid": "keseey9x", "rank": 21, "score": 8.531200408935547}, {"content": "Title: Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India Content: BACKGROUND AND AIMS: During the current pandemic of COVID-19, India is under lockdown which could cause disruption in diet and lifestyle in patients with type 2 diabetes (T2DM). We aimed to study lifestyle changes and other common issues related to treatment in our previously seen and treated patients with T2DM. METHODS: Patients (n, 150) who were regularly following up before lockdown were interviewed telephonically (after 45 days of start of lockdown) regarding lifestyle changes, stress and other diabetes-related questions. RESULT: Carbohydrate consumption and frequency of snacking increased in 21% and 23% patients, respectively. Interestingly, 27% patients reported an increase in consumption of fruits. Exercise duration was reduced in 42% and weight gain occurred in 19% patients. Frequency of doing self-monitoring of blood glucose (SMBG) was decreased in 23% patients. 'Mental stress' of any kind was reported in 87% patients. Availability of medicines and insulin was uninterrupted in 91% patients. Knowledge about telemedicine was present in 69% and majority (92%) of these patients preferred video consultation. CONCLUSION: During 45 days of lockdown increase in carbohydrate intake, decrease in exercise, decreased SMBG and widespread mental stress in patients with T2DM was recorded, factors which may destabilize or exacerbate hyperglycemia and hypertension. Some positive changes (e.g. increased intake of fruits) were also observed.", "qid": 24, "docid": "s1eo9qdi", "rank": 22, "score": 8.53119945526123}, {"content": "Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10\u201331 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 \u00b1 13.0 years, median BMI 28.4 (25th\u201375th percentile: 25.0\u201332.7) kg/m(2); with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin\u2013angiotensin\u2013aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA(1c), diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.", "qid": 24, "docid": "97j1gt5k", "rank": 23, "score": 8.458900451660156}, {"content": "Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 \u00b1 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.", "qid": 24, "docid": "hlnjp7v6", "rank": 24, "score": 8.45889949798584}, {"content": "Title: Clinical Outcomes of Metabolic Surgery: Microvascular and Macrovascular Complications. Content: Understanding of the long-term clinical outcomes associated with bariatric surgery has recently been advanced. Research related to the sequelae of diabetes-in particular, long-term microvascular and macrovascular complications-in patients who undergo weight-loss surgery is imperative to this pursuit. While numerous randomized control trials have assessed glucose control with bariatric surgery compared with intensive medical therapy, bariatric surgery outcome data relating to microvascular and macrovascular complications have been limited to observational studies and nonrandomized clinical trials. As a result, whether bariatric surgery is associated with a long-term reduction in microvascular and macrovascular complications when compared with current intensive glycemic control therapy cannot be determined because the evidence is insufficient. However, the consistent salutary effects of bariatric surgery on diabetes remission and glycemic improvement support the opportunity (and need) to conduct high-quality studies of bariatric surgery versus intensive glucose control. This review provides relevant background information related to the treatment of diabetes, hyperglycemia, and long-term complications; reports clinical findings (to date) with bariatric surgery; and identifies ongoing research focusing on long-term vascular outcomes associated with bariatric surgery.", "qid": 24, "docid": "0t9uspl5", "rank": 25, "score": 8.413599967956543}, {"content": "Title: Is health related quality of life influenced by diabetic neuropathic pain among type II diabetes mellitus patients in Ethiopia? Content: BACKGROUND Polyneuropathy is one of the commonest complications of long-standing diabetes. Progressive sensory loss can predispose patients to foot ulcer and the neuropathy oftentimes causes pain. The pain can significantly affect the quality of life of patients. OBJECTIVES To describes the health-related quality of life of patients with type II diabetes mellitus suffering from painful diabetic peripheral neuropathy at two referral hospitals in Addis Ababa, Ethiopia, 2017. METHODS An institution based cross sectional study with internal comparison was conducted among a sample of 220 type II diabetes mellitus patients in a 1:1 matched ratio of those with and without diabetes associated peripheral neuropathic pain. All were having regular follow up at two hospitals in Addis Ababa, Ethiopia. The Short Form (SF-36) health-related quality of life instrument was used to collect data on quality of life while basic socio-demographic and other disease specific features were collected using a structured questionnaire. Descriptive statistics was used to examine the mean scores of health related quality of life. Cronbach's alpha coefficient and Pearson's correlation coefficient were applied to estimate the internal consistency, and the level of agreement between the different domains of SF-36, respectively. To measure association between health related quality of life domains and explanatory variables, independent T-test and ANOVA were performed followed by multiple linear regression analyses. RESULTS The health related quality of life of type II diabetes mellitus patients with peripheral neuropathic pain was poorer than those without pain in all the eight domains and the two summary scores by SF-36 (p < 0.001). Higher mean score difference was observed in Mental Component Summary Score (MCS) (14.6) compared to Physical Component Score (PCS) (9.3). Among the eight domains, the largest mean difference was found with the physical one (39.1) followed by mental health (38.2) and physical functioning (30). Pain intensity had a statistically significant negative correlation with all domains as well as the two summary scores. Younger age, a higher level of education, being single, a higher monthly income, normal body mass index, HbA1c less than seven mmo/L, absence of other diabetic complications and taking only oral hypoglycemic agents were found to predict better health related quality of life. CONCLUSION The presence of diabetic peripheral neuropathic pain was found to negatively influence the health-related quality of life of type II diabetic patients; the greatest impact being on the 'role physical' and 'mental health' domains. Older age, presence of diabetes related complications, longer duration of illness negatively influenced the health-related quality of life.", "qid": 24, "docid": "t13vx0ls", "rank": 26, "score": 8.3951997756958}, {"content": "Title: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.", "qid": 24, "docid": "9uymi395", "rank": 27, "score": 8.38070011138916}, {"content": "Title: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation. Content: The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.", "qid": 24, "docid": "an3apm5g", "rank": 28, "score": 8.331000328063965}, {"content": "Title: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation Content: The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.", "qid": 24, "docid": "j5glp7xc", "rank": 29, "score": 8.330999374389648}, {"content": "Title: [Diabetes and COVID-19 infection] Content: Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection Antidiabetic therapy may need adjustments following usual sick day rules Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection", "qid": 24, "docid": "m9d88do0", "rank": 30, "score": 8.325900077819824}, {"content": "Title: [Diabetes and COVID-19 infection]. Content: Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.", "qid": 24, "docid": "nih2cnnz", "rank": 31, "score": 8.325899124145508}, {"content": "Title: A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine Content: Blacks/African Americans are overrepresented in the number of hospitalizations and deaths from COVID-19 in the United States, which could be explained through differences in the prevalence of existing comorbidities. We performed a disease-disease phenome-wide association study (PheWAS) using data representing 5,698 COVID-19 patients from a large academic medical center, stratified by race. We explore the association of 1,043 pre-occurring conditions with several COVID-19 outcomes: testing positive, hospitalization, ICU admission, and mortality. Obesity, iron deficiency anemia and type II diabetes were associated with susceptibility in the full cohort, while ill-defined descriptions/complications of heart disease and stage III chronic kidney disease were associated among non-Hispanic White (NHW) and non-Hispanic Black/African American (NHAA) patients, respectively. The top phenotype hits in the full, NHW, and NHAA cohorts for hospitalization were acute renal failure, hypertension, and insufficiency/arrest respiratory failure, respectively. Suggestive relationships between respiratory issues and COVID-19-related ICU admission and mortality were observed, while circulatory system diseases showed stronger association in NHAA patients. We were able to replicate some known comorbidities related to COVID-19 outcomes while discovering potentially unknown associations, such as endocrine/metabolic conditions related to hospitalization and mental disorders related to mortality, for future validation. We provide interactive PheWAS visualization for broader exploration.", "qid": 24, "docid": "915x3q19", "rank": 32, "score": 8.32229995727539}, {"content": "Title: Potential Benefits and Harms of Novel Antidiabetic Drugs during COVID-19 Crisis Content: Patients with diabetes have been reported to have enhanced susceptibility to severe or fatal COVID-19 infections, including a high risk of being admitted to intensive care units with respiratory failure and septic complications. Given the global prevalence of diabetes, affecting over 450 million people worldwide and still on the rise, the emerging COVID-19 crisis poses a serious threat to an extremely large vulnerable population. However, the broad heterogeneity and complexity of this dysmetabolic condition, with reference to etiologic mechanisms, degree of glycemic derangement and comorbid associations, along with the extensive sexual dimorphism in immune responses, can hamper any patient generalization. Even more relevant, and irrespective of glucose-lowering activities, DPP4 inhibitors and GLP1 receptor agonists may have a favorable impact on the modulation of viral entry and overproduction of inflammatory cytokines during COVID-19 infection, although current evidence is limited and not univocal. Conversely, SGLT2 inhibitors may increase the likelihood of COVID-19-related ketoacidosis decompensation among patients with severe insulin deficiency. Mindful of their widespread popularity in the management of diabetes, addressing potential benefits and harms of novel antidiabetic drugs to clinical prognosis at the time of a COVID-19 pandemic deserves careful consideration.", "qid": 24, "docid": "ao50s1k2", "rank": 33, "score": 8.3125}, {"content": "Title: Potential Benefits and Harms of Novel Antidiabetic Drugs During COVID-19 Crisis Content: Patients with diabetes have been reported to have enhanced susceptibility to severe or fatal COVID-19 infections, including a high risk of being admitted to intensive care units with respiratory failure and septic complications. Given the global prevalence of diabetes, affecting over 450 million people worldwide and still on the rise, the emerging COVID-19 crisis poses a serious threat to an extremely large vulnerable population. However, the broad heterogeneity and complexity of this dysmetabolic condition, with reference to etiologic mechanisms, degree of glycemic derangement and comorbid associations, along with the extensive sexual dimorphism in immune responses, can hamper any patient generalization. Even more relevant, and irrespective of glucose-lowering activities, DPP4 inhibitors and GLP1 receptor agonists may have a favorable impact on the modulation of viral entry and overproduction of inflammatory cytokines during COVID-19 infection, although current evidence is limited and not univocal. Conversely, SGLT2 inhibitors may increase the likelihood of COVID-19-related ketoacidosis decompensation among patients with severe insulin deficiency. Mindful of their widespread popularity in the management of diabetes, addressing potential benefits and harms of novel antidiabetic drugs to clinical prognosis at the time of a COVID-19 pandemic deserves careful consideration.", "qid": 24, "docid": "oypck6de", "rank": 34, "score": 8.312499046325684}, {"content": "Title: Use Stones from Another Mountain to Polish One\u2019s Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ \u4e2d\u534e\u5185\u5206\u6ccc\u4ee3\u8c22\u6742\u5fd7 Content: Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19.", "qid": 24, "docid": "eqewn6j4", "rank": 35, "score": 8.2121000289917}, {"content": "Title: Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association\u2013European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.", "qid": 24, "docid": "3bvtcdja", "rank": 36, "score": 8.20580005645752}, {"content": "Title: Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.", "qid": 24, "docid": "ln9xw11k", "rank": 37, "score": 8.205799102783203}, {"content": "Title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review Content: AIMS: Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to the glycemic control, and role of anti-diabetic agents in patients with diabetes. METHODS: A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. RESULTS: There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. CONCLUSIONS: Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.", "qid": 24, "docid": "dlv0kyb2", "rank": 38, "score": 8.205400466918945}, {"content": "Title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A Narrative Review Content: Abstract Aims Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to glycemic control and role of anti-diabetic agents in patients with diabetes. Methods A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. Results There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe variety of COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. Conclusions Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.", "qid": 24, "docid": "k5ro0edf", "rank": 39, "score": 8.205399513244629}, {"content": "Title: Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study Content: AIMS: The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. METHODS: In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. RESULTS: Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR] = 3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR = 1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. CONCLUSIONS: Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "qid": 24, "docid": "8ydwzl4z", "rank": 40, "score": 8.174400329589844}, {"content": "Title: Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study Content: Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "qid": 24, "docid": "c2jm0g88", "rank": 41, "score": 8.174399375915527}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of \u226411mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of \u22651.5 \u03bcg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of \u226510 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \ufeffmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 24, "docid": "5m4ybd1v", "rank": 42, "score": 8.169400215148926}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of &#8804;11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of &#8805;1.5 \u00b5g/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of &#8805;10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \u00ef\u00bb\u00bfmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 24, "docid": "nmolo7rt", "rank": 43, "score": 8.16939926147461}, {"content": "Title: Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study Content: Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (\u2265 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs. 31.2%), coronary heart disease (17.1% vs. 8.0%), and chronic kidney diseases (6.2% vs. 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs. 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs. 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol\u00b7L(-1) (interquartile range (IQR): 5.80\u20139.29) vs. 5.46 mmol\u00b7L(-1) (IQR: 5.00\u20136.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol\u00b7L(-1) (IQR: 1.67\u20132.76) vs. 1.75 mmol\u00b7L(-1) (IQR: 1.27\u20132.01)), and systolic pressure (130 mmHg (IQR: 120\u2013142) vs. 122 mmHg (IQR: 110\u2013137), P = 0.001) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.", "qid": 24, "docid": "fhpvshr2", "rank": 44, "score": 8.119600296020508}, {"content": "Title: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Content: Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.", "qid": 24, "docid": "skknfc6h", "rank": 45, "score": 8.080100059509277}, {"content": "Title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19 Content: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient\u2013provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.", "qid": 24, "docid": "e38nu08a", "rank": 46, "score": 8.01509952545166}, {"content": "Title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19 Content: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.", "qid": 24, "docid": "u9jffox1", "rank": 47, "score": 8.015098571777344}, {"content": "Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication Content: OBJECTIVE: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. RESULTS: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. CONCLUSIONS: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "qid": 24, "docid": "p3qsn8di", "rank": 48, "score": 8.012900352478027}, {"content": "Title: Case report of chloroquine therapy and hypoglycaemia in type 1 diabetes: What should we have in mind during the COVID-19 pandemic? Content: Abstract A type 1 diabetes patient experienced remission associated with chloroquine therapy while travelling to a malaria-endemic area. Chloroquine has immunomodulatory and hypoglycaemic effects and may become more frequently used due to the COVID-19 pandemic. Patients with type 1 diabetes treated with chloroquine should be monitored for hypoglycaemia, even after recovery.", "qid": 24, "docid": "u4di2tk7", "rank": 49, "score": 8.009599685668945}, {"content": "Title: Case report of chloroquine therapy and hypoglycaemia in type 1 diabetes: What should we have in mind during the COVID-19 pandemic? Content: A type 1 diabetes patient experienced remission associated with chloroquine therapy while travelling to a malaria-endemic area. Chloroquine has immunomodulatory and hypoglycaemic effects and may become more frequently used due to the COVID-19 pandemic. Patients with type 1 diabetes treated with chloroquine should be monitored for hypoglycaemia, even after recovery.", "qid": 24, "docid": "z9hifitw", "rank": 50, "score": 8.009598731994629}, {"content": "Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31\u20132.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "qid": 24, "docid": "f0lo04qq", "rank": 51, "score": 8.008399963378906}, {"content": "Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31-2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "qid": 24, "docid": "ibpyqrq4", "rank": 52, "score": 8.00839900970459}, {"content": "Title: Modifying Risk Factors: Strategies That Work Diabetes Mellitus. Content: An estimated 29.1 million Americans are currently diagnosed with diabetes, and this number is expected to increase to 48.3 million Americans by 2050. Correspondingly, the present burden of diabetes among patients undergoing total joint arthroplasty is significant and rising. Diabetes as a chronic condition is a well-established risk factor for complication after total joint arthroplasty. A growing body of evidence also indicates that hyperglycemia in the perioperative period, and not the diagnosis of diabetes alone, is similarly associated with increased complication risk. As a result, a coordinated approach to preoperative screening and optimization, combined with judicious perioperative glycemic control, may present an opportunity to improve outcomes, reduce complications, and avoid complication-related costs for patients undergoing total joint arthroplasty.", "qid": 24, "docid": "zeo9l272", "rank": 53, "score": 7.986999988555908}, {"content": "Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Content: OBJECTIVE Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTS The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONS C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "qid": 24, "docid": "p536yuvi", "rank": 54, "score": 7.959400177001953}, {"content": "Title: The global diabetes epidemic: what does it mean for infectious diseases in tropical countries? Content: Summary Tropical countries are experiencing a substantial rise in type 2 diabetes, which is often undiagnosed or poorly controlled. Since diabetes is a risk factor for many infectious diseases, this increase probably adds to the large infectious disease burden in tropical countries. We reviewed the literature to investigate the interface between diabetes and infections in tropical countries, including the WHO-defined neglected tropical diseases. Although solid data are sparse, patients with diabetes living in tropical countries most likely face increased risks of common and health-care-associated infections, as well as infected foot ulcers, which often lead to amputation. There is strong evidence that diabetes increases the severity of some endemic infections such as tuberculosis, melioidosis, and dengue virus infection. Some HIV and antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. But there are no or very scarce data for most tropical infections and for possible biological mechanisms underlying associations with diabetes. The rise in diabetes and other non-communicable diseases puts a heavy toll on health systems in tropical countries. On the other hand, complications common to both diabetes and some tropical infections might provide an opportunity for shared services\u2014for example, for eye health (trachoma and onchocerciasis), ulcer care (leprosy), or renal support (schistosomiasis). More research about the interaction of diabetes and infections in tropical countries is needed, and the infectious disease burden in these countries is another reason to step up global efforts to improve prevention and care for diabetes.", "qid": 24, "docid": "n52mmprb", "rank": 55, "score": 7.941199779510498}, {"content": "Title: COVID-19 and type 1 diabetes: dealing with the difficult duo Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. The bulk of the evolving evidence in diabetes and COVID-19 relates to type 2 diabetes (T2D). Since there are a significant number of patients with type 1 diabetes (T1D) with unique concerns and challenges during the ongoing COVID-19 pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. METHODS: We systematically searched the PubMed database up to May 31, 2020, and retrieved all the articles published on T1D and COVID-19. RESULTS: We found 18 relevant articles, each of which carried a part of the evidence regarding the risk of contracting COVID-19 in patients with T1D, effect of COVID-19 on development of T1D, outcomes in T1D with COVID-19, and special management issues in T1D in the light of COVID-19. These have been documented in the present review. CONCLUSION: COVID-19 with T1D presents special challenges. While the available evidence does shed some light, we need more evidence to deal with this difficult duo.", "qid": 24, "docid": "l9hfmmbc", "rank": 56, "score": 7.894000053405762}, {"content": "Title: Is the epidemic spread related to GDP? Visualizing the distribution of COVID-19 in Chinese Mainland Content: In December 2019, COVID-19 were detected in Wuhan City, Hubei Province of China. SARS-CoV-2 rapidly spread to the whole Chinese mainland with the people during the Chinese Spring Festival Travel Rush. As of 19 February 2020, 74576 confirmed cases of COVID-19 had been reported in Chinese Mainland. What kind of cities have more confirmed cases, and is there any relationship between GDP and confirmed cases? In this study, we explored the relationship between the confirmed cases of COVID-19 and GDP at the prefectural-level, found a positive correlation between them. This finding warns high GDP areas should pay more prevention and control efforts when an epidemic outbreak, as they have greater risks than other areas nearby.", "qid": 24, "docid": "go442ycb", "rank": 57, "score": 7.867599964141846}, {"content": "Title: Mechanism of inflammatory response in associated comorbidities in COVID-19 Content: BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.", "qid": 24, "docid": "cn3bpmwj", "rank": 58, "score": 7.861299991607666}, {"content": "Title: Risk factors for mortality in pregnant women with SARS-CoV-2 infection Content: Since the first case of pneumonia was described, SARS-CoV-2 infection (coronavirus disease [COVID]-19) rapidly spread worldwide With 94,288 infections and more than 10,000 deaths, Mexico is the third Latin-American country in number of confirmed cases and second in mortality1. A major risk factor for adverse outcome in COVID-19 infection is the presence of advance age, co-morbidities including diabetes, hypertension and obesity among other non-communicable diseases2. Epidemiological data from high-prevalence countries reveal that compared to men, women are less likely to die or to require hospital admission to intensive care. This may suggest that pregnant women are not more susceptible to infection or to experience serious complications. However, whether the presence of co-morbidities or advanced maternal age confers a higher risk of adverse outcome in pregnant women with COVID-19 is unknown3. In this research letter, we aimed at evaluating the risk factor associated with maternal mortality secondary to COVID-19 infection in a middle-income country. Advanced maternal age is linked to an increased risk of mortality, while diabetes is the most important risk factor for maternal death. This is partly explained by an increasing incidence of non-communicable diseases in women of advanced age which is a common feature in most countries4. In the last decades, low- and middle-income countries have experienced accelerated socio-cultural changes associated with its incorporation into the international economic community, which have increased the number of obese and diabetic population, including pregnant women5. This has caused an increased risk for complications and fatality among COVID-19 positive population2,3. Thus, policies for reducing obesity and diabetes in low- and middle-income countries are most needed to reduce the mortality of COVID-19 in pregnant women.", "qid": 24, "docid": "1hmnx2re", "rank": 59, "score": 7.836699962615967}, {"content": "Title: Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis Content: INTRODUCTION: and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. MATERIALS AND METHODS: A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. RESULTS: The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. CONCLUSION: The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.", "qid": 24, "docid": "n71hyyad", "rank": 60, "score": 7.808499813079834}, {"content": "Title: Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis Content: Abstract Introduction and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. Materials and methods A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. Results The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. Conclusion The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.", "qid": 24, "docid": "stmo4b0g", "rank": 61, "score": 7.808498859405518}, {"content": "Title: Diabetes is a risk factor for the progression and prognosis of COVID-19 Content: BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.", "qid": 24, "docid": "ix2vjgph", "rank": 62, "score": 7.771100044250488}, {"content": "Title: Diabetes is a risk factor for the progression and prognosis of COVID\u201019 Content: BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID\u201019). METHODS: A total of 174 consecutive patients confirmed with COVID\u201019 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID\u201019 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury\u2010related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation\u2010related biomarkers such as IL\u20106, C\u2010reactive protein, serum ferritin and coagulation index, D\u2010dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID\u201019. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID\u201019. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.", "qid": 24, "docid": "wizlpkrk", "rank": 63, "score": 7.771099090576172}, {"content": "Title: Mini-gastric bypass to control morbid obesity and diabetes mellitus: what radiologists need to know. Content: Laparoscopic mini-gastric bypass surgery is a safe and simple surgical intervention for treating morbid obesity and diabetes mellitus and is now being performed more frequently. Radiologists must be critical in their postoperative evaluation of these patients. In this pictorial review, we explain and illustrate the surgical technique, normal postoperative anatomy, and associated complications as seen on imaging examinations, including fluoroscopy and computed tomography.", "qid": 24, "docid": "ry4jkltc", "rank": 64, "score": 7.765200138092041}, {"content": "Title: Pharmacovigilance in Patients with Diabetes: A Data-Driven Analysis Identifying Specific RAS Antagonists with Adverse Pulmonary Safety Profiles That Have Implications for COVID-19 Morbidity and Mortality Content: ABSTRACT OBJECTIVES Current demographic information from China reports that 10-19% of patients hospitalized with COVID-19 were diabetic. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) are considered first-line agents in diabetics due to their nephroprotective effects but administration of these drugs leads to upregulation of angiotensin-converting-enzyme-2 (ACE2), responsible for viral entry of severe-acute-respiratory-distress-syndrome, coronavirus-2 (SARS-CoV-2). Data is lacking to determine what pulmonary effects ACEIs/ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. In this study, the aim was to assess the prevalence of pulmonary adverse drug effects (ADEs) in diabetic patients taking ACEI or ARBs to help provide guidance as to how these medications could affect outcomes in acute respiratory illness, such as SARS-CoV-2 infection. METHODS 1DATA, a unique data platform resulting from collaboration across veterinary and human healthcare, utilized an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases, to evaluate all ADEs reported to the FDA for patients with diabetes taking ACEIs or ARBs. RESULTS Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid healthcare professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system specifically, COVID-19. Based on this data mining, Captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared to other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. CONCLUSION These analyses suggest that pharmacists and clinicians will need to consider specific medication\u2019s adverse event profile, particularly captopril, and how this profile may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.", "qid": 24, "docid": "0j5828ah", "rank": 65, "score": 7.752200126647949}, {"content": "Title: Pharmacovigilance in patients with diabetes: A data-driven analysis identifying specific RAS antagonists with adverse pulmonary safety profiles that have implications for COVID-19 morbidity and mortality Content: OBJECTIVES: The current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered first-line agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection. METHODS: 1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs. RESULTS: Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. CONCLUSION: These analyses suggest that pharmacists and clinicians will need to consider the specific medication's adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.", "qid": 24, "docid": "mojxv2iw", "rank": 66, "score": 7.752199172973633}, {"content": "Title: COVID-19 and diabetes from IDF MENA region Content: The whole world are facing the current COVID-19 pandemic, the most serious health crisis in modern times. All countries with the support of national and international agencies are making great efforts to fight this devastating pandemic with disastrous medical, economic and social consequences. This pandemic affects all people but it's serious in case of diabetes, elderly and in chronic and complicated diseases. The current work on the theme \" COVID-19 and Diabetes\" attempts to bring together all the data available at MENA level through medical and scientific publications. It also includes all the efforts made by the governments and the responses of associations and their efforts in this field. Even if it is admitted that diabetes with its comorbidity represents a high risk factor for severe forms and mortality, the health consequences of the epidemic, does not seem as dramatic in terms of both morbidity and mortality of COVID-19 with diabetes in the majority of MENA countries. If the crises continues longer, the supply of insulin, oral drugs, self monitoring equipment of diabetes and other tools, will be affected. To this, we must expect great difficulties in supplying food for many countries. Certainely, it is important to remember that containment and hygiene measures, associated with other factors such as the young average age of the population, the higher temperature in these countries, the differences in the immune status of populations and the role of BCG vaccine have something to do with it. All of this deserves to be studied in depth.", "qid": 24, "docid": "8vn01luq", "rank": 67, "score": 7.751399993896484}, {"content": "Title: Enforced inactivity in the elderly and diabetes risk: initial estimates of the burden of an unintended consequence of COVID-19 lockdown Content: Background: Older adults and those with underlying health conditions were advised to stay at home to help reduce the spread of COVID-19 however little advice on regular physical activity was given to those at risk. We modelled the effects of enforced inactivity on diabetes burden using published evidence. Methods: Using Health Survey for England data, we estimated the prevalence of pre-diabetes and physical activity in adults aged 70 and older. The number of new diabetes cases directly attributed to lockdown were calculated using population attributable risk. Unit cost estimates of the additional burden on primary care and the cost of complications to secondary care were taken from the literature. Results: From 9 million older (aged 70yrs and above) people living in England, 2.1 million could be defined as pre-diabetic (glycated haemoglobin > 42 < 48 mmol/mol). The estimated population attributable fraction (0.281) (assuming relative risk of diabetes from inactivity, 3.3; 40% physically active pre-lockdown) would give rise to 392,948 new cases of diabetes which we argue are directly attributed to a prolonged period of lockdown. We estimate that the cost of screening and testing these patients in primary care (GBP 35m), their subsequent treatment and management (GBP 229m), and complications (GBP 909m) would equate to an additional GBP 1.17bn to the health care system. Conclusions: Inactivity related to lockdown in previously active older adults may contribute up to GBP 1.17b in additional healthcare costs through a potential increase in diabetes. Clear advice about the importance of physical activity may reduce this potential economic burden during global pandemics.", "qid": 24, "docid": "9k6pjml1", "rank": 68, "score": 7.694900035858154}, {"content": "Title: Hypoglycemia at the time of Covid-19 pandemic Content: BACKGROUND: Hypoglycemia is the limiting factor in the glycemic management of diabetes, which need to be addressed critically to avoid complications. Lockdown because of new coronavirus strain (COVID-19) pandemic has further complicated the issue of hypoglycemia due to limitations in access to food, outpatient clinics, pathological services and medicines. AIM: To assess the factors associated with the risk of hypoglycemia during April\u2013May 2020 lockdown in people with type 2 diabetes mellitus. METHODOLOGY: We analyzed the data retrospectively from 146 patients of type 2 diabetes mellitus (T2DM) reporting to the emergency department (ED) during lockdown period with symptoms suggestive of hypoglycemia. RESULTS: The majority of patients were male (90/146) with a mean age of 59.88 \u00b1 10.09 years and a mean random blood glucose level of 57.67 \u00b1 9.00 mg/dL. Two-third of patients (70.83%) had level 1 hypoglycemia, while level 2 hypoglycemia was reported in 29.16% of patients. A combination of Metformin and Sulfonylureas (SU) was most commonly associated with the risk of hypoglycemia (65.75%) followed by insulin (33.56%). Subjects who received insulin reported a lower blood glucose value (50.75 \u00b1 8.20 mg/dL) as compared to those receiving a combination of metformin and SU (60.95 \u00b1 7.10 mg/dl). 330.56% of patients who had received prophylaxis hydroxychloroquine (HCQ) 400 mg twice a day along with the routine anti-hyperglycemic agents without their dose adjustment reported hypoglycemia. Patients with hypertension, micro-vascular, macro-vascular complications, and coexistent with each other had a higher propensity to the risk of hypoglycemia (46.58%, 33.56%, 23.29%, and 32.88%) respectively. CONCLUSION: The COVID-19 lockdown has shown to influence the risk of hypoglycemia in patients with T2DM, especially those receiving SU, insulin, HCQ especially in patients with associated co-morbidities. Patient education, support, and telemedicine plays a pivotal role to prevent hypoglycemia.", "qid": 24, "docid": "moi0hu6l", "rank": 69, "score": 7.682499885559082}, {"content": "Title: Diabetes-related symptoms, acute complications and management of diabetes mellitus of patients who are receiving palliative care: a protocol for a systematic review. Content: INTRODUCTION Worldwide, an estimated 40 million people are in need of palliative care each year, but only 14% receive it. The incidence of diabetes mellitus (DM) in patients receiving palliative care is higher than in the general population. This association is intended to grow as a result of the rising burden of DM worldwide, ageing populations and the improved overall survival time of several diseases over the last few decades. Recommendations for DM management in the context of palliative care are mainly based on expert opinion as there is a lack of suitable evidence base and randomised clinical trials in palliative care are scarce. The aim of our systematic review is to identify the best DM management practices in order to reduce important DM-related symptoms and acute complications in patients receiving palliative care. METHODS AND ANALYSIS The authors will study the DM treatment and management literature, surveying the different approaches employed to treat adult palliative patients. Core health bibliographic databases will be searched from January 1990 to May 2019. Data sources will include Ovid MEDLINE, Embase, PubMed, Web of Sciences, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, Cumulative Index to Nursing and Allied Health Literature and grey literature. Details regarding diet, oral and injectable glucose-lowering medicines, insulin regimens and blood glucose monitoring strategies will be evaluated. We defined the primary outcomes to compare between DM management approaches as the presence of symptoms (polyuria, polydipsia and polyphagia) and acute complications of DM (hypoglycaemia, hyperglycaemic hyperosmolar state and diabetic ketoacidosis), and secondary outcomes as hospital admissions and deaths due to DM-related complications, health-related quality of life and glycaemic control. ETHICS AND DISSEMINATION The systematic review methodology does not require ethics approval due to the nature of the study design. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available. PROSPERO REGISTRATION NUMBER CRD42018115772.", "qid": 24, "docid": "1qxq71w0", "rank": 70, "score": 7.679500102996826}, {"content": "Title: Epidemiology of haemodialysis catheter complications: a survey of 865 dialysis patients from 14 haemodialysis centres in Henan province in China. Content: OBJECTIVES To investigate the incidence rates and risk factors for catheter-related complications in different districts and populations in Henan Province in China. DESIGN Cross-sectional. SETTING Fourteen hospitals in Henan Province. PARTICIPANTS 865 patients with renal dysfunction undergoing dialysis using catheters between October 2013 and October 2014. MAIN OUTCOME MEASURES The main outcome measures were complications, risk factors and patient characteristics. Catheter-related complications included catheter-related infection (catheter exit-site infection, catheter tunnel infection and catheter-related bloodstream infection), catheter dysfunction (thrombosis, catheter malposition or kinking, and fibrin shell formation) and central vein stenosis. RESULTS The overall incidence rate was 7.74/1000 catheter-days, affecting 38.61% of all patients, for catheter infections, 10.58/1000 catheter-days, affecting 56.65% of all patients, for catheter dysfunction, and 0.68/1000 catheter-days, affecting 8.79% of all patients, for central vein stenosis. Multivariate analysis showed that increased age, diabetes, primary educational level or below, rural residence, lack of a nephropathy visit before dialysis and pre-established permanent vascular access, not taking oral drugs to prevent catheter thrombus, lower serum albumin levels and higher ferritin levels were independently associated with catheter infections. Rural residence, not taking oral drugs to prevent thrombus, lack of an imaging examination after catheter insertion, non-tunnel catheter type, lack of medical insurance, lack of nephropathy visit before dialysis and pre-established permanent vascular access, left-sided catheter position, access via the femoral vein and lower haemoglobin level were independently associated with catheter dysfunction. Diabetes, lack of nephropathy visit before dialysis and pre-established permanent vascular access, lack of oral drugs to prevent catheter thrombus, left-sided catheter location and higher number of catheter insertions, were independently associated with central vein stenosis. CONCLUSIONS The rate of catheter-related complications was high in patients with end-stage renal disease in Henan Province. Our finding suggest that strategies should be implemented to decrease complication rates.", "qid": 24, "docid": "o3gks1iq", "rank": 71, "score": 7.657400131225586}, {"content": "Title: Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients Content: Diabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs. In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.", "qid": 24, "docid": "gfx7zi53", "rank": 72, "score": 7.618800163269043}, {"content": "Title: COVID-19 in diabetic patients: related risks and specifics of management Content: Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "qid": 24, "docid": "0tsefy6p", "rank": 73, "score": 7.595600128173828}, {"content": "Title: COVID-19 in diabetic patients: Related risks and specifics of management Content: Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "qid": 24, "docid": "lfdeowsl", "rank": 74, "score": 7.595599174499512}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge Content: BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS: This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19 METHODS: The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy RESULTS: The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue;while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19 CONCLUSIONS: The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress", "qid": 24, "docid": "lqfzte7w", "rank": 75, "score": 7.592599868774414}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge. Content: BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.", "qid": 24, "docid": "r4c7nldn", "rank": 76, "score": 7.592598915100098}, {"content": "Title: Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications Content: OBJECTIVES: Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. METHODS: All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. RESULTS: Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. CONCLUSIONS: The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. [Figure: see text]", "qid": 24, "docid": "l8bj9twb", "rank": 77, "score": 7.5868000984191895}, {"content": "Title: Rodent animal models: from mild to advanced stages of diabetic nephropathy Content: Diabetic nephropathy (DN) is a secondary complication of both type 1 and type 2 diabetes, resulting from uncontrolled high blood sugar. 30\u201340 % of diabetic patients develop DN associated with a poor life expectancy and end-stage renal disease, causing serious socioeconomic problems. Although an exact pathogenesis of DN is still unknown, several factors such as hyperglycemia, hyperlipidemia, hypertension and proteinuria may contribute to the progression of renal damage in diabetic nephropathy. DN is confirmed by measuring blood urea nitrogen, serum creatinine, creatinine clearance and proteinuria. Clinical studies show that intensive control of hyperglycemia and blood pressure could successfully reduce proteinuria, which is the main sign of glomerular lesions in DN, and improve the renal prognosis in patients with DN. Diabetic rodent models have traditionally been used for doing research on pathogenesis and developing novel therapeutic strategies, but have limitations for translational research. Diabetes in animal models such as rodents are induced either spontaneously or by using chemical, surgical, genetic, or other techniques and depicts many clinical features or related phenotypes of the disease. This review discusses the merits and demerits of the models, which are used for many reasons in the research of diabetes and diabetic complications.", "qid": 24, "docid": "642pa6sl", "rank": 78, "score": 7.529900074005127}, {"content": "Title: THERAP\u2013COVID-19 Content: Summary According to previous reports, diabetes seems to be associated with serious clinical events due to COVID-19. But is diabetes per se a risk factor of being infected by the virus? We discuss these points. Data about the antidiabetic drugs are scarce. Dipeptidylpeptidase-4 (DPP-4) is found as both a cell surface protein ubiquitously expressed in many tissues and as a soluble molecule found in serum/plasma, fluids. DPP-4 is involved in infection of cells by some viruses. We relate data about the use of DPP-4 inhibitors in diabetic patients. We conclude relating French and international recommendations in people with diabetes.", "qid": 24, "docid": "dudf192x", "rank": 79, "score": 7.528600215911865}, {"content": "Title: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis Content: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.", "qid": 24, "docid": "mez1k8t0", "rank": 80, "score": 7.488800048828125}, {"content": "Title: COVID-19 and diabetes: What does the clinician need to know? Content: COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.", "qid": 24, "docid": "ff04vt1d", "rank": 81, "score": 7.486599922180176}, {"content": "Title: COVID-19 does not stop obstetrics: what we need to change to go on safely birthing. The experience of a University Obstetrics and Gynecology Department in Milan. Content: Since SARS-COV-2 appeared in Wuhan City, China and rapidly spread throughout Europe, a real revolution occurred in the daily routine and in the organization of the entire health system. While non-urgent clinical services have been reduced as far as possible, all kind of specialists turned into COVID-19 specialists. Obstetric assistance cannot be suspended and, at the same time, safety must be guaranteed. In addition, as COVID-19 positive pregnant patients require additional care, some of the clinical habits need to be changed to face emerging needs for a vulnerable but unstoppable kind of patients. We report the management set up in an Obstetrics and Gynecology Unit during the COVID-19 era in a University Hospital in Milan, Italy.", "qid": 24, "docid": "jf9whlu7", "rank": 82, "score": 7.4791998863220215}, {"content": "Title: COVID-19 does not stop obstetrics: what we need to change to go on safely birthing. The experience of a University Obstetrics and Gynecology Department in Milan Content: Since SARS-COV-2 appeared in Wuhan City, China and rapidly spread throughout Europe, a real revolution occurred in the daily routine and in the organization of the entire health system. While non-urgent clinical services have been reduced as far as possible, all kind of specialists turned into COVID-19 specialists. Obstetric assistance cannot be suspended and, at the same time, safety must be guaranteed. In addition, as COVID-19 positive pregnant patients require additional care, some of the clinical habits need to be changed to face emerging needs for a vulnerable but unstoppable kind of patients. We report the management set up in an Obstetrics and Gynecology Unit during the COVID-19 era in a University Hospital in Milan, Italy.", "qid": 24, "docid": "zd3niwqc", "rank": 83, "score": 7.479198932647705}, {"content": "Title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review Content: Objective: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. Data sources: Google Scholar, PubMed, COVID-19 Open Research Dataset: a resource of over 128,000 scholarly articles, including over 59,000 articles with full text related to COVID-19, SARS-CoV-2, and coronaviruses. Methods: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. The search engine was built using a retrieval function that ranks a set of documents based on the query terms appearing in each document regardless of their proximity within the document. Filtering of the articles was then undertaken using keywords and questions, e.g. \"Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?\". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. Findings: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Such reports could lead many oncologists and physicians to change their treatment strategies without solid evidence and recommendations. Further research regarding this relationship and its clinical management is warranted. Additionally, treatment options must be examined further to provide optimal treatment and ensure better outcomes for patients suffering from these comorbidities. It should be noted that, whether definitive measurements exist or not, the care of patients as well as the research involved should be largely prioritized to tackle this deadly pandemic.", "qid": 24, "docid": "kc8xff5n", "rank": 84, "score": 7.473100185394287}, {"content": "Title: Clinical characteristics and outcome in patients with combined diabetic ketoacidosis and hyperosmolar hyperglycemic state associated with COVID-19: A retrospective, hospital-based observational case series Content: AIM: One of the risk factors for poor outcome with SARS-CoV-2 infection is diabetes mellitus; diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious complications of diabetes mellitus. We aimed to explore the clinical characteristics and outcomes of COVID-19 patients presenting with combined DKA/HHS to our institution. METHODS: A retrospective, hospital based observation case series was performed on patients with SARS-CoV-2 admitted to Intensive Care Unit between 3/20/2020 and 4/20/2020. Inclusion criteria were: (1) Blood Glucose >250 mg/dL; (2) Serum bicarbonate <18 mmol/L; (3) Anion Gap >10; (4) serum pH <7.3; (5) ketonemia or ketonuria; (6) effective/calculated plasma osmolality >304 mOsm/kg and (7) positive SARS-CoV-2 RT-PCR. RESULTS: We reported 6 patients who presented during this period with combined DKA/HHS. Their median age was 50 years, all males, three Hispanic, and three African American. Hispanic patients, had more severe acidosis, and multiple comorbidities, with a higher mortality. The striking feature was that combined DKA/HHS was the initial presentation for COVID-19 for most of the cases. DISCUSSION: Our observational retrospective case series shows that diabetic patients are at risk of developing combined DKA/ HHS associated with COVID-19 and a substantial mortality. To our knowledge, we are first to report the clinical characteristics and outcome in this group of patients.", "qid": 24, "docid": "pswgxtwd", "rank": 85, "score": 7.471799850463867}, {"content": "Title: Clinical Characteristics and Outcome in Patients with Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Associated with COVID-19: A Retrospective, Hospital-Based Observational Case Series Content: AIM: One of the risk factors for poor outcome with SARS-CoV-2 infection is diabetes mellitus; diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious complications of diabetes mellitus. We aimed to explore the clinical characteristics and outcomes of COVID-19 patients presenting with combined DKA/HHS to our institution. METHODS: A retrospective, hospital based observation case series was performed on patients with SARS-CoV-2 admitted to Intensive Care Unit between 3/20/2020 and 4/20/2020. Inclusion criteria were: 1) Blood Glucose >250mg/dL; 2) Serum bicarbonate <18 mmol/L; 3) Anion Gap >10; 4) serum pH <7.3 ; 4) ketonemia or ketonuria; 5) effective/calculated plasma osmolality >304 mOsm/kg. and 6) positive SARS-CoV-2 RT-PCR RESULTS: We reported 6 patients who presented during this period with combined DKA/HHS. Their median age was 50 years, all males, three Hispanic, and three African American. Hispanic patients, had more severe acidosis, and multiple comorbidities, with a higher mortality. The striking feature was that combined DKA/HHS was the initial presentation for COVID-19 for most of the cases. DISCUSSION: Our observational retrospective case series shows that diabetic patients are at risk of developing combined DKA/ HHS associated with COVID-19 and a substantial mortality. To our knowledge, we are first to report the clinical characteristics and outcome in this group of patients.", "qid": 24, "docid": "z4p2z2qy", "rank": 86, "score": 7.471798896789551}, {"content": "Title: COVID\u201019 and Older Adults: What We Know Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), a novel virus that causes COVID\u201019 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin\u2010converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE\u20102 receptor, the very receptor that the SARS\u2010CoV\u20102 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID\u201019 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID\u201019 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926\u2013929, 2020", "qid": 24, "docid": "kd4uxcve", "rank": 87, "score": 7.464900016784668}, {"content": "Title: COVID-19 and Older Adults: What We Know Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes COVID-19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor that the SARS-CoV-2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID-19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID-19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926-929, 2020.", "qid": 24, "docid": "vhfl6l6k", "rank": 88, "score": 7.464899063110352}, {"content": "Title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Content: BACKGROUND AND AIMS: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). METHODS: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. CONCLUSION: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "qid": 24, "docid": "1y78dfsl", "rank": 89, "score": 7.463900089263916}, {"content": "Title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Content: Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "qid": 24, "docid": "7kw9lws0", "rank": 90, "score": 7.4638991355896}, {"content": "Title: COVID-19 and diabetes: What have we learned so far? Content: COVID-19 and diabetes are both pandemics with major impacts on global public health. While the response to COVID-19 has been rapid and progressive to reduce risk of harm, the response to the diabetes pandemic has been somewhat more muted. People with diabetes have been disproportionately affected by COVID-19, with growing evidence of higher mortality and morbidity. In this article, we discuss the impact of COVID-19 on our diabetes service in an urban area in the UK. We discuss the impact on our patients and ourselves, and the possible lessons we can carry into the future.", "qid": 24, "docid": "dbclnrwr", "rank": 91, "score": 7.433199882507324}, {"content": "Title: How scientific research reacts to international public health emergencies: a global analysis of response patterns Content: As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.", "qid": 24, "docid": "h4vigeuy", "rank": 92, "score": 7.426599979400635}, {"content": "Title: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study Content: BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of \u226570 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.", "qid": 24, "docid": "fvc7hfhg", "rank": 93, "score": 7.417099952697754}, {"content": "Title: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study Content: BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of &#8805;70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.", "qid": 24, "docid": "q73o1sns", "rank": 94, "score": 7.4170989990234375}, {"content": "Title: Cerebral Venous Thrombosis Associated with COVID-19. Content: Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.", "qid": 24, "docid": "6d3jcf6o", "rank": 95, "score": 7.414000034332275}, {"content": "Title: Cerebral Venous Thrombosis Associated with COVID-19 Content: Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.", "qid": 24, "docid": "iuy2i3bs", "rank": 96, "score": 7.413999080657959}, {"content": "Title: Use of a bioprosthetic mesh in complex hernia repair: early results from a French multicenter pilot study. Content: BACKGROUND Implantation of synthetic meshes for reinforcement of abdominal wall hernias can be complicated by mesh infection, which often requires mesh explantation. The risk of mesh infection is increased in a contaminated environment or in patients who have comorbidities such as diabetes or smoking. The use of biological prostheses has been advocated because of their ability to resist infection. Initial results, however, have shown high hernia recurrence rates and wound occurrences. The objective of the present study is to evaluate early and mid-term outcomes in the largest French series that included 43 consecutive complex abdominal hernias repaired with biological prostheses. MATERIALS AND METHODS Retrospective observational study of a prospective collected data bank. Patient demographics, history of previous repairs, intraoperative findings and degree of contamination, associated procedures, postoperative prosthetic-related complications, and long-term results were retrospectively reviewed. RESULTS There were 25 (58%) incisional, 14 parastomal, and 4 midline hernia repairs. Hernias were considered \"clean\" (n = 5), \"clean-contaminated\" (n = 19), \"contaminated\" (n = 12), or \"dirty\" (n = 7). Wound-related morbidity occurred in 17 patients; 4 patients needed reoperation for cutaneous necrosis or abscess. Smoking was the only risk factor associated with wound complication (P = .022). No postoperative wound events required removal of the prosthesis. There were 4 hernia recurrences (9%). A previous attempt at repair (P = .018) and no complete fascia closure (P = .033) were associated with hernia recurrence. CONCLUSIONS This study demonstrated that the use of bioprothesis in complex hernia repair allowed successful single-stage reconstruction. Wound-related complications were frequent. Cost-benefit analyses are important to establish the validity of these findings.", "qid": 24, "docid": "4r0y9mgv", "rank": 97, "score": 7.412399768829346}, {"content": "Title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review Content: BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. \u201cEffects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?\u201c. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.", "qid": 24, "docid": "ab5tgbvm", "rank": 98, "score": 7.412299156188965}, {"content": "Title: Infecci\u00f3n por coronavirus en pacientes con diabetes Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus;2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes;3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2", "qid": 24, "docid": "5ps6pw6c", "rank": 99, "score": 7.40500020980835}, {"content": "Title: Coronavirus infection in patients with diabetes. Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins. Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death. The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy. Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections. Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality. In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus; 2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes; 3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2.", "qid": 24, "docid": "ifmwfm43", "rank": 100, "score": 7.404999256134033}]}
{"query": "which biomarkers predict the severe clinical course of 2019-nCOV infection?", "hits": [{"content": "Title: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury Content: The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.", "qid": 25, "docid": "9k8r18x7", "rank": 1, "score": 13.839699745178223}, {"content": "Title: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury Content: The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.", "qid": 25, "docid": "t996fbad", "rank": 2, "score": 13.688899993896484}, {"content": "Title: Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage Content: Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age \u2265 50 and NLR < 3.13 patients, and half of patients with age \u2265 50 and NLR \u2265 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age \u2265 50 and NLR \u2265 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.", "qid": 25, "docid": "pd70i3d8", "rank": 3, "score": 11.352700233459473}, {"content": "Title: Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Content: Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV\u2019s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.", "qid": 25, "docid": "85acs4lk", "rank": 4, "score": 10.931300163269043}, {"content": "Title: Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Content: Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.", "qid": 25, "docid": "tfz6f32q", "rank": 5, "score": 10.913399696350098}, {"content": "Title: The role of biomarkers in diagnosis of COVID-19 - A systematic review Content: AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "qid": 25, "docid": "aph6yf7n", "rank": 6, "score": 10.894599914550781}, {"content": "Title: The role of biomarkers in diagnosis of COVID-19 \u2013 A systematic review Content: AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included \u2018COVID-19\u2019, \u2018SARS-CoV2\u2019, \u2018Biomarkers\u2019, among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "qid": 25, "docid": "r8mn4lzv", "rank": 7, "score": 10.894598960876465}, {"content": "Title: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.", "qid": 25, "docid": "etaa9a1v", "rank": 8, "score": 10.503499984741211}, {"content": "Title: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS: Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.", "qid": 25, "docid": "ou7hpqjd", "rank": 9, "score": 10.503499031066895}, {"content": "Title: Clinical Analysis of 25 COVID-19 Infections in Children Content: BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 \u00d7 10/L and 2 cases (8%) less than 4 \u00d7 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 \u00b1 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.", "qid": 25, "docid": "38699x1n", "rank": 10, "score": 10.49269962310791}, {"content": "Title: Clinical Analysis of 25 Novel Coronavirus Infections in Children Content: BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 \u00d7 10/L and 2 cases (8%) less than 4 \u00d7 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 \u00b1 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.", "qid": 25, "docid": "ogcfgy8f", "rank": 11, "score": 10.492698669433594}, {"content": "Title: Clinical Analysis of 25 Novel Coronavirus Infections in Children. Content: BACKGROUND To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 \u00d7 10/L and 2 cases (8%) less than 4 \u00d7 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 \u00b1 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.", "qid": 25, "docid": "yydc7ksy", "rank": 12, "score": 10.492697715759277}, {"content": "Title: Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm Content: The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it. It is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.", "qid": 25, "docid": "t9bt70f2", "rank": 13, "score": 10.491600036621094}, {"content": "Title: Using IL\u20102R/lymphocytes for predicting the clinical progression of patients with COVID\u201019 Content: Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease\u20102019 (COVID\u201019) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID\u201019 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C\u2010reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)\u20102R, IL\u20106, IL\u20108, IL\u201010 and tumor necrosis factor (TNF)\u2010\u03b1] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL\u20102R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL\u20102R to lymphocytes was found to be remarkably increased in severe and critical patients. IL\u20102R/lymphocytes were superior compared with other markers for the identification of COVID\u201019 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL\u20102R/lymphocytes were significantly decreased in recovered patients, but further increased in disease\u2010deteriorated patients, which might be correlated with the outcome of COVID\u201019. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL\u20102R/lymphocyte was a prominent biomarker for early identification of severe COVID\u201019 and predicting the clinical progression of the disease.", "qid": 25, "docid": "7dy95eta", "rank": 14, "score": 10.450699806213379}, {"content": "Title: Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19 Content: Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-&#945;] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.", "qid": 25, "docid": "wesk2dhi", "rank": 15, "score": 10.450698852539062}, {"content": "Title: Coronavirus disease (COVID-19): Rheumatological Prospects/Relevance Content: In December 2019, an outbreak of a novel infection under the working name 2019-nCoV was registered in Wuhan (the Hubei Province located in China's central region), which has quickly spread throughout almost the entire world and become pandemic. The World Health Organization (WHO) proposed a new name coronavirus disease (COVID-19) for this disease, whereas the International Committee on Virus Taxonomy renamed 2019-nCov as SARS-Cov-2 (Severe Acute Respiratory Syndrome Coronavirus-2). The development of the COVID-19 pandemic is not only of great social importance, but also draws the attention of a medical community to the fundamentally new clinical and fundamental problems of the immunopathology of human diseases that are yet to be formulated. The unique experience gained in rheumatology from studies of the pathogenetic mechanisms and pharmacotherapy of immune-mediated inflammatory rheumatic diseases (IMIRDs) can be of great importance for deciphering the nature of the pathological processes that underlie the severe, potentially fatal complications of COVID-19, and may assist in improving their therapy. As for prospects in patients with IMIRDs, although the development of COVID-19 in the presence of IMIRDs has not yet fortunately been described, infection with SARS-CoV-2, like other viruses, can be assumed to cause an exacerbation of the pathological process, whereas severe immune system pathology and comorbidities can worsen the course of infection. Since, according to the current concepts, it is the \u00abhyperimmune\u00bb response, and not just the effect only of the virus itself, that underlies lung damage and deaths from COVID-19, special attention is drawn to the effects of antirheumatic therapy that includes glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), biological agents, and targeted DMARDs, which can have a multidirectional effect on the course of COVID-19. There are significant theoretical prerequisites for the repurposing of some drugs widely used in rheumatology for the treatment of COVID-19 and its complications. Consideration is given to the prospects of studying the immunopathology of COVID-19 and to the theoretical justifications for the use of antimalarial 4-aminoquinolines, anti-cytokine monoclonal antibodies (mAbs), and Janus kinase inhibitors for the prevention of complications and for the treatment of COVID-19.", "qid": 25, "docid": "k3wkb1gn", "rank": 16, "score": 10.311100006103516}, {"content": "Title: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events Content: BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (\u2265 1.5 fold, P \u2264 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a \u2265 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.", "qid": 25, "docid": "o32d3kaw", "rank": 17, "score": 10.29580020904541}, {"content": "Title: ACE2 variants underlie interindividual variability and susceptibility to COVID-19 in Italian population Content: In December 2019, an initial cluster of unexpected interstitial bilateral pneumonia emerged in Wuhan, Hubei province. A human-to-human transmission was immediately assumed and a previously unrecognized entity, termed coronavirus disease 19 (COVID-19) due to a novel coronavirus (2019-nCov) was suddenly described. The infection has rapidly spread out all over the world and Italy has been the first European Country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has recently been shown that 2019-nCov utilizes host receptors namely angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined around 7000 exomes from 5 different Centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three missense changes, p.Asn720Asp, p.Lys26Arg, p.Gly211Arg (MAF 0.002 to 0.015), which have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants likely interfering with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. These findings suggest that a predisposing genetic background may contribute to the observed inter-individual clinical variability associated with COVID-19. They allow an evidence-based risk assessment opening up the way to personalized preventive measures and therapeutic options.", "qid": 25, "docid": "klj710h2", "rank": 18, "score": 10.249199867248535}, {"content": "Title: 2019-NCoV: What Every Neurologist Should Know? Content: The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early \u2013 headache, dizziness, hyposmia and hypogeusia and late \u2013 encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV.", "qid": 25, "docid": "ml80nllo", "rank": 19, "score": 10.23289966583252}, {"content": "Title: Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020 Content: Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.", "qid": 25, "docid": "60qmiwjm", "rank": 20, "score": 10.231300354003906}, {"content": "Title: Prediction of 2019-nCov in Italy based on PSO and inversion analysis Content: Although China achieved an early victory of controlling the novel coronavirus (2019-nCov), the overseas situation is overwhelming negative, especially in Italy. Up to March 11, 2020, 2019-nCov thoroughly broke out in Italy with over 10,000 confirmed cases notwithstanding the gradually block of the country since March 9, 2020. Estimation of possible infection population and prospective suggestion of handling spread based on exist data are of crucial importance. Considering of the biology parameters obtained based on Chinese clinical data in Wuhan, other scholars' work and real spread feature of 2019-nCov in Italy, we built a more applicable model called SEIJR with log-normal distributed time delay to forecast the trend of spreading. Adopting Particle Swarm Optimization (PSO), we estimated the early period average spreading velocity (0) and conducted inversion analysis of time point (T0) when the virus first hit the Italy. Based on fixed 0 and T0, we then obtained the average spreading velocity 1 after the lock by PSO. For the aim of offering expeditious advice, we generated the prediction trends with different which we considered would be helpful in addressing the infection. Not only solved the complex, nondifferentiable equation of epidemic model, our research also performs well in inversion analysis based on PSO which conveys informative outcomes for further discussion on precatious action. To conclude, the first day of spread is around February 1, 2020 with the early period average spreading velocity 0=0.330 which is higher than most cities in China except Wuhan. After locking the country and attaching great attention to public precaution, the 1 sharply descended to 0.278, indicting the effectiveness of these measures. Furthermore, in order to cope the disease before mid-April, take actions to control the under 0.25 is necessary. Code can be freely download from https://github.com/Summerwork/2019-nCov-Prediction.", "qid": 25, "docid": "gj518ja2", "rank": 21, "score": 10.225199699401855}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-\u03b1), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "0deyspy2", "rank": 22, "score": 10.210000038146973}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-\u03b1), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "iprkszdn", "rank": 23, "score": 10.209999084472656}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia] Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-&#945;), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "wmlme0f4", "rank": 24, "score": 10.20999813079834}, {"content": "Title: Mozliwosci kontrolowania zakazenia nowym wirusem Corona \u00ad 2019-nCoV./ [Options for controlling new Corona virus infection - 2019-nCoV] Content: According to the Situation Report 65 of the World Health Organization of March 25, 2020, the COVID-19 incidence rate indicates 413 467 confirmed cases and 18 433 deaths. Genetic diversification of the Corona virus has resulted in strains that cause severe respiratory tract infections in humans via drip and animal mediation. S-proteins covering its surface, which bind to the cell receptor - angiotensin converting enzyme 2 (ACE-2) and transmembrane serine protease (TMPRSS2) are important in shaping virus activity. The course of infection varies from mild to severe. The ability to control infection is limited because there are no drugs that fully inhibit 2019-nCoV. Interferon-alpha (5 million U twice daily by inhalation), lopinavir/ritonavir (400/100 mg twice daily orally), as well as chloroquine (500 mg twice daily orally for 10 days) and azithromycin (500 mg twice per day) cause a milder course of the disease and reduce the duration of treatment. The administration of glucocorticosteroids and research drugs (tocilizumab) is acceptable for massive infiltrative lesions in the pulmonary parenchyma causing severe lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the system operation it is necessary to create the socalled a safety matrix that would take into account the existing threat on the one hand and all available services and resources on the other. Precise analysis and separation of individual tasks can enable the creation of a real crisis management plan.", "qid": 25, "docid": "dpe9ld92", "rank": 25, "score": 10.208000183105469}, {"content": "Title: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Content: Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55\u00b75 years (SD 13\u00b71), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.", "qid": 25, "docid": "m40kwgcg", "rank": 26, "score": 10.161100387573242}, {"content": "Title: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Content: BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55\u00b75 years (SD 13\u00b71), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China.", "qid": 25, "docid": "vndydx85", "rank": 27, "score": 10.161099433898926}, {"content": "Title: [From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment] Content: COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases had been found. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases,authors proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which were related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "qid": 25, "docid": "a290vxor", "rank": 28, "score": 10.123600006103516}, {"content": "Title: [From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment]. Content: COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases. They proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which are related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "qid": 25, "docid": "qpwu24e8", "rank": 29, "score": 10.1235990524292}, {"content": "Title: Network-Based Prediction of the 2019-nCoV Epidemic Outbreak in the Chinese Province Hubei Content: At the moment of writing (12 February, 2020), the future evolution of the 2019-nCoV virus is unclear. Predictions of the further course of the epidemic are decisive to deploy targeted disease control measures. We consider a network-based model to describe the 2019-nCoV epidemic in the Hubei province. The network is composed of the cities in Hubei and their interactions (e.g., traffic flow). However, the precise interactions between cities is unknown and must be inferred from observing the epidemic. We propose a network-based method to predict the future prevalence of the 2019-nCoV virus in every city. Our results indicate that network-based modelling is beneficial for an accurate forecast of the epidemic outbreak.", "qid": 25, "docid": "5uvv46mi", "rank": 30, "score": 10.069299697875977}, {"content": "Title: Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases Content: Objective To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection Methods The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR Results Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV One premature infant was transferred to Department of Neonatology due to low birth weight By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment) There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction No pathological change of villitis and chorioamnionitis was observed in our observation of three cases All samples from three placentas were negative for the nucleic acid of 2019-nCoV Conclusions The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation Pathological study suggests that there are no morphological changes related to infection in the three placentas Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy", "qid": 25, "docid": "6l87fij9", "rank": 31, "score": 10.043299674987793}, {"content": "Title: [Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases] Content: Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy,and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology by February 4, 2020 were retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.", "qid": 25, "docid": "djw2zzk6", "rank": 32, "score": 10.043298721313477}, {"content": "Title: [Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases]. Content: Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.", "qid": 25, "docid": "gsc0ukst", "rank": 33, "score": 10.04329776763916}, {"content": "Title: Clinical characteristics of 2019 novel coronavirus infection in China Content: Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.", "qid": 25, "docid": "tovfd9lw", "rank": 34, "score": 9.958600044250488}, {"content": "Title: The diagnostic value of joint detection of serum IgMand IgG antibodies to 2019-nCoV in 2019-nCoV infection/ \u4e2d\u534e\u68c0\u9a8c\u533b\u5b66\u6742\u5fd7 Content: Objective@#To investigate the diagnostic value of immunoglobulin M (IgM) and immunoglobulin G(IgG) antibodies to 2019 Novel Coronavirus (2019-nCoV) in 2019-nCoV infection.@*Method@#This is a retrospective study. Serum samples were collected from 284 patients including outpatients and inpatients in the Renmin Hospital of Wuhan University from January 20, 2020 to February 17, 2020. Among them 205 cases were 2019-nCoV infected patients, including 186 cases confirmed with nucleic acid test and 19 cases diagnosed by clinical symptoms and CT characteristics according to &quot;the New Coronavirus Pneumonia Control Protocol (5th edition)&quot; . A total of 79 subjects with other diseases but negative to 2019-nCoV infection were recruited as control group. Serum IgM and IgG antibodies to 2019-nCoV were measured with fully automated immunoassay technology for all subjects. Statistical significance between 2019-nCoV antibodies test and 2019-nCoV nucleic acid test was determined using the &#x03C7;2 tests.@*Result@#The sensitivity of serum IgM and IgG antibodies to 2019-nCoV were 70.24%(144/205) and 96.10%(197/205) respectively and the specificity were 96.20%(76/79) and 92.41%(73/79) respectively. The positive and negative predictive values of 2019-nCoV antibodies were 95.63%(197/206) and 91.03% (71/78) respectively, and the positive and negative predictive values of 2019-nCoV nucleic acid test were 100%(186/186) and 80.61%(79/98) respectively. The total coincidence rate of diagnosing 2019-nCoV infection between antibody tests and nucleic acid test for 2019-nCoV were 88.03%(250/284).@*Conclusion@#Joint detection of serum IgM and IgG antibodies to 2019-nCoV is an effective screening and diagnostic indicators for 2019-nCoV infection, and an effective complement to the false negative results to nucleic acid test.", "qid": 25, "docid": "zzljrkbf", "rank": 35, "score": 9.95419979095459}, {"content": "Title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Content: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of 2019-nCoV; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.", "qid": 25, "docid": "vogum3ir", "rank": 36, "score": 9.837499618530273}, {"content": "Title: A link between inflammatory biomarkers and lung ultrasound observations in patients with SARS-CoV-2 infection Content: ABSTRACT: Lung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate a potential association between lung lesions visualised by LUS and blood biomarkers as well as the ability to predict mortality from two different lung ultrasound scoring systems (LUSS). We performed a retrospective observational study on 45 patients aged >70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. The correlation between biochemical parameters and either LUSS score was significant for ferritin levels. It was 0.486 (p=0.001) for LUSS8 and 0.458 (p=0.002) for LUSS12. Using a threshold score of 15 with LUSS12 predicted mortality in 86.7% of cases (ORcrude 31, CI 95% 4.79-200.51). Applying a threshold of 10 with LUSS8 predicted mortality in 88.9% (ORcrude 69.75, CI 95% 6.90-705.20). There is a correlation between ferritin levels and LUSS. The prognostic capacity of LUSS12 does not surpass that of LUSS8.", "qid": 25, "docid": "gw767i37", "rank": 37, "score": 9.780699729919434}, {"content": "Title: A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital Content: Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks' treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.", "qid": 25, "docid": "e5uyahea", "rank": 38, "score": 9.757699966430664}, {"content": "Title: A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital Content: Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks\u2019 treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.", "qid": 25, "docid": "o6bkxn7l", "rank": 39, "score": 9.757699012756348}, {"content": "Title: [Options for controlling new Corona virus infection - 2019-nCoV]. Content: According to the Situation Report 65 of the World Health Organization of March 25, 2020, the COVID-19 incidence rate indicates 413 467 confirmed cases and 18 433 deaths. Genetic diversification of the Corona virus has resulted in strains that cause severe respiratory tract infections in humans via drip and animal mediation. S-proteins covering its surface, which bind to the cell receptor - angiotensin converting enzyme 2 (ACE-2) and transmembrane serine protease (TMPRSS2) are important in shaping virus activity. The course of infection varies from mild to severe. The ability to control infection is limited because there are no drugs that fully inhibit 2019-nCoV. Interferon-alpha (5 million U twice daily by inhalation), lopinavir/ritonavir (400/100 mg twice daily orally), as well as chloroquine (500 mg twice daily orally for 10 days) and azithromycin (500 mg twice per day) cause a milder course of the disease and reduce the duration of treatment. The administration of glucocorticosteroids and research drugs (tocilizumab) is acceptable for massive infiltrative lesions in the pulmonary parenchyma causing severe lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the system operation it is necessary to create the socalled a safety matrix that would take into account the existing threat on the one hand and all available services and resources on the other. Precise analysis and separation of individual tasks can enable the creation of a real crisis management plan.", "qid": 25, "docid": "xj7z6zk1", "rank": 40, "score": 9.757200241088867}, {"content": "Title: Specific Serum Markers of IPF: What Is the Significance of KL-6, SP-A, and SP-D? Content: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. It is characterized by the progressive worsening of lung function and has a poor prognosis (median survival is approximately 3 years). However, the clinical course of disease shows considerable individual variability. Therefore, it is important to monitor the clinical course and to predict prognosis for optimal therapy. Serum biomarkers are both less invasive and reproducible diagnostic tools. Useful biomarkers for patients with IPF are strongly coveted; however, to date, there are no biomarkers that are globally known. In Japan, surfactant protein (SP)-A, SP-D, and KL-6 are commonly used as serum markers of interstitial pneumonia, including IPF, in the clinical setting, and empirical data has been accumulated over 10 years. SP-A and SP-D are hydrophilic proteins and members of the collectin family. These collectins have been shown to function as host defense lectins in the lung. KL-6 is a high molecular weight glycoprotein and now classified as a human MUC1 mucin protein. These three proteins are mainly synthesized by alveolar type II cells. The mechanisms of increase for these protein levels in sera of patients with IPF are probably a combination of a loss of epithelial integrity due to injury and an increased mass of type II cells due to hyperplasia. It has been revealed that those proteins are useful for monitoring the clinical course and predicting prognosis as well as for the diagnosis of IPF. In this review article, the molecular structures and biological functions of these biomarkers are outlined, and we discuss the clinical application of these biomarkers for patients with IPF.", "qid": 25, "docid": "18jiikdq", "rank": 41, "score": 9.729100227355957}, {"content": "Title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target Content: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.", "qid": 25, "docid": "m15m1xh8", "rank": 42, "score": 9.704500198364258}, {"content": "Title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Content: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.", "qid": 25, "docid": "og92zxnf", "rank": 43, "score": 9.704499244689941}, {"content": "Title: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study. Content: Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "qid": 25, "docid": "nqee1shq", "rank": 44, "score": 9.675200462341309}, {"content": "Title: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study Content: Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "qid": 25, "docid": "rkm6c8z6", "rank": 45, "score": 9.675199508666992}, {"content": "Title: SYSTEMATIC REVIEW OF THE ONGOING CLINICAL TRIALS EVALUATING THE DIAGNOSTIC AND THERAPEUTIC INTERVENTIONS TO MANAGE THE RESPIRATORY INFECTION CAUSED BY 2019 NOVEL CORONAVIRUS (2019-NCOV) Content: TYPE: Abstract Publication TOPIC: Respiratory Care PURPOSE: 2019 novel coronavirus (2019-nCoV) is attributed for outbreak with first human infection detected in December 2019 in Wuhan, China, which has caused clusters of severe respiratory illness like severe acute respiratory syndrome coronavirus. The latest mortality was 2.07%. Currently, the standard care is supportive care, and no treatment is proven to be effective METHODS: We systematically analysed the contemporary protocols of the seven ongoing trials through the Chinese Clinical Trial Registry (4 trials) and the trials registry (3 trials) database. The latest evaluation was on January 29, 2020 with key word \u20182019-nCoV\u2019, for the trials evaluating the diagnostic and the therapeutic interventions to manage the respiratory infection caused by 2019-nCoV RESULTS: Therapeutic interventions include, lopinavir-ritonavir with aerosolized interferon-alpha compared with the adjunctive IV methylprednisolone, umifenovir (broad-spectrum antiviral), SARI-nCoV trial for role of glucocorticoid, three comparative antiviral therapies utilising ribavirin, interferon alpha-1b, lopinavir -ritonavir, Xue-Bi-Jing injection (only Chinese medicine injection approved for sepsis) and novel isothermal nucleic acid amplification technique is under trial for simple, fast and portable diagnosis. The mean number of patients being enrolled is 193 (SD \u00b1 183, maximum 500, minimum 40, range 460, 95% CI 24 to 362). Cumulatively, 1350 patients are targeted across 7 trials. CONCLUSIONS: Varied novel approaches based on the current scientific understanding of the disease are being evaluated for quick and effective management CLINICAL IMPLICATIONS: As the 2019-nCoV becomes a global threat, the rapidity of the Chinese trials for an evidence-based approach are in direction to provide rational, efficacious and potential solutions to effectively manage the disease DISCLOSURE: No significant relationships. KEYWORDS: Ongoing Trials, Systematic Review, 2019-nCoV", "qid": 25, "docid": "7r01gnot", "rank": 46, "score": 9.653599739074707}, {"content": "Title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Content: Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1\u03b1, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.", "qid": 25, "docid": "8ceabd6e", "rank": 47, "score": 9.64680004119873}, {"content": "Title: Functional assessment of cell entry and receptor usage for lineage B \u03b2-coronaviruses, including 2019-nCoV Content: Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS- CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.", "qid": 25, "docid": "tyhwtt7j", "rank": 48, "score": 9.62660026550293}, {"content": "Title: Clinical characteristics of 50466 patients with 2019-nCoV infection Content: Objective: We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results: Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion: Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).", "qid": 25, "docid": "aoi4iqkf", "rank": 49, "score": 9.62399959564209}, {"content": "Title: Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction deep learning model Content: The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.", "qid": 25, "docid": "cszqykpu", "rank": 50, "score": 9.617500305175781}, {"content": "Title: Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019\u2010nCoV Content: OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019\u2010nCoV). METHODS: Based on the susceptible\u2010exposed\u2010infected\u2010removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019\u2010nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real\u2010time reports on the number of 2019\u2010nCoV\u2010infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019\u2010nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.", "qid": 25, "docid": "bhjc1jcs", "rank": 51, "score": 9.611900329589844}, {"content": "Title: Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019-nCoV Content: OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). METHODS: Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real-time reports on the number of 2019-nCoV-infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019-nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.", "qid": 25, "docid": "fp6fhijm", "rank": 52, "score": 9.611899375915527}, {"content": "Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01-01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of a dysregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "qid": 25, "docid": "i4t1jq29", "rank": 53, "score": 9.584400177001953}, {"content": "Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "qid": 25, "docid": "qzev2reb", "rank": 54, "score": 9.584399223327637}, {"content": "Title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Content: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-\u00ce\u00b3-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-\u00ce\u00b3-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.", "qid": 25, "docid": "7rjzontt", "rank": 55, "score": 9.522199630737305}, {"content": "Title: A comparative-descriptive analysis of clinical characteristics in 2019-coronavirus-infected children and adults Content: Acute respiratory disease caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-2019-nCoV acute respiratory diseases were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%), and 1 (4%), respectively. The median incubation period of children and adults was 5 days (ranged, 3-12 days) and 4 days (ranged, 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were demic by World Health Organiza more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5%, 71.4%) was roughly the same as adults (20%, 80%). A total of 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs 4%, P=.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019-nCoV disease, but also for a future discussion on age-specific coronavirus infection.", "qid": 25, "docid": "ltdfyzay", "rank": 56, "score": 9.506999969482422}, {"content": "Title: Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening Content: 2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.", "qid": 25, "docid": "iu2ziccm", "rank": 57, "score": 9.501899719238281}, {"content": "Title: Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV Content: OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of \"2019-nCoV, SARS-CoV, and MERS-CoV\" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.", "qid": 25, "docid": "ovmso3qu", "rank": 58, "score": 9.5}, {"content": "Title: Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV. Content: OBJECTIVE Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS The data on the global outbreak of \"2019-nCoV, SARS-CoV, and MERS-CoV\" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.", "qid": 25, "docid": "zppc6p20", "rank": 59, "score": 9.499999046325684}, {"content": "Title: D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19 Content: A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 \u00c53 on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easily to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.", "qid": 25, "docid": "45pp83im", "rank": 60, "score": 9.497699737548828}, {"content": "Title: Statistics based predictions of coronavirus 2019-nCoV spreading in mainland China Content: Background. The epidemic outbreak cased by coronavirus 2019-nCoV is of great interest to researches because of the high rate of spread of the infection and the significant number of fatalities. A detailed scientific analysis of the phenomenon is yet to come, but the public is already interested in the questions of the duration of the epidemic, the expected number of patients and deaths. For long time predictions, the complicated mathematical models are necessary which need many efforts for unknown parameters identification and calculations. In this article, some preliminary estimates will be presented. Objective. Since the reliable long time data are available only for mainland China, we will try to predict the epidemic characteristics only in this area. We will estimate some of the epidemic characteristics and present the most reliable dependences for victim numbers, infected and removed persons versus time. Methods. In this study we use the known SIR model for the dynamics of an epidemic, the known exact solution of the linear equations and statistical approach developed before for investigation of the children disease, which occurred in Chernivtsi (Ukraine) in 1988-1989. Results. The optimal values of the SIR model parameters were identified with the use of statistical approach. The numbers of infected, susceptible and removed persons versus time were predicted. Conclusions. Simple mathematical model was used to predict the characteristics of the epidemic caused by coronavirus 2019-nCoV in mainland China. The further research should focus on updating the predictions with the use of fresh data and using more complicated mathematical models.", "qid": 25, "docid": "bhm2un6v", "rank": 61, "score": 9.47439956665039}, {"content": "Title: 2019 Coronavirus pandemic in Turkey and across the world/ D\u00fcnyada ve T\u00fcrkiye'de 2019 Koronavir\u00fcs Pandemisi Content: The novel coronavirus, which was called 2019-nCoV at the beginning of the outbreak, was named SARS-CoV-2 later. The clinical disease caused by the virus was also called Coronavirus disease 2019 (COVID-19). World Health Organization declared COVID-19 a global pandemic on 11.03.2020. As of 26.03.2020, there have been 462.684 confirmed cases and 20.834 deaths globally, and these numbers are expected to increase in the coming days. The dynamics of virus spread are investigated with various models and outbreak parameters such as incubation time and basic reproduction number (R0) is tried to be illuminated. According to official numbers, as of 03.26.2020, there have also been 3629 cases and 75 deaths in Turkey. COVID-19 Guideline prepared by the Ministry of Health of the Republic of Turkey is constantly updated with additional prevention and treatment strategies. Various predictions are made for the future course of the pandemic, and the contribution of the spread of the virus in Africa and seasonal changes on this issue has been investigated.", "qid": 25, "docid": "xxnasobj", "rank": 62, "score": 9.456199645996094}, {"content": "Title: Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) Content: The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.", "qid": 25, "docid": "b1iyr42n", "rank": 63, "score": 9.437299728393555}, {"content": "Title: Treatment to prevent the development of severe COVID-19 Content: The respiratory virus infection COVID-19 caused by the new coronavirus SARS-CoV2 has been reported in China since December 2019 It has been reported that COVID-19 tends to be more severe in the elderly and in patients with underlying diseases including diabetes, heart disease, and chronic lung disease In severe cases, patients require intensive cares including mechanical ventilation in the ICUs So far, no biomarker that predicts the severity, or no therapeutic strategies to prevent the development of severe diseases has been established Pathology of severe COVID-19 has two aspects: viral overgrowth and excess pulmonary inflammation For the former, clinical trials using existing drugs such as remdesivir (nucleic acid drug), lopinavir/ritonavir combination drug (protease inhibitor), favipravir (polymerase inhibitor), and interferon (antiviral drugs) are being conducted in patients with severe COVID-19 in China Furthermore the interest has been focused on immune globulin preparations enriched with pathogen-specific antibodies collected from the plasma of recovered patients For the latter, clinical studies using tocilizumab (IL-6 receptor antibody) and ACE2 protein have been conducted with the purpose of reducing excessive inflammation of the lung In addition, single cell analysis of immune cells and comprehensive repertoire analysis of TCR/BCR using patient blood are in progress overseas, which are useful to elucidate the mechanism of the severe disease progression and identify the useful biomarkers for it", "qid": 25, "docid": "flfnpzsd", "rank": 64, "score": 9.406000137329102}, {"content": "Title: Clinical Perspective on 2019 Novel Coronavirus Pneumonia: A Systematic Review of Published Case Reports Content: The ongoing pandemic of 2019 novel coronavirus (2019-nCoV), which originated from Wuhan, China, has led to 68,279 deaths due to 2019-nCoV pneumonia as of May 5, 2020. We conducted a systematic review and included 16 case reports to summarize the transmission and pathology of 2019-nCoV, and clinical presentation, laboratory and imaging findings, and treatment in 2019-nCoV pneumonia. The disease is mild in most people; in some, it may progress to severe pneumonia with acute respiratory distress syndrome (ARDS). Patients with mild illness usually recover at home, with supportive care and isolation in accordance with guidelines. Patients who have moderate to severe pneumonia are usually monitored in the hospital. Although there is no definitive treatment for 2019-nCoV pneumonia so far, some antiviral drugs have shown promising results. The use of lopinavir/ritonavir and remdesivir was associated with significant clinical improvement in severe pneumonia. Nonetheless, we need more randomized clinical trials (RCTs) and treatment guidelines for developing effective management of the 2019-nCoV and improve patient outcomes by reducing mortality in high-risk patients. We also need \ufeffmore clinical trials and management guidelines for the effective management of 2019-nCoV pneumonia.", "qid": 25, "docid": "xv7fun4g", "rank": 65, "score": 9.385499954223633}, {"content": "Title: Protein Chip Array Profiling Analysis in Patients with Severe Acute Respiratory Syndrome Identified Serum Amyloid A Protein as a Biomarker Potentially Useful in Monitoring the Extent of Pneumonia Content: Background: A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients. Methods: We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals. Results: Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11 695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild. Conclusions: Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.", "qid": 25, "docid": "9ij6cned", "rank": 66, "score": 9.38070011138916}, {"content": "Title: Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr law Content: Background: The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China. Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful. Farr law is a classic epidemiology theory/practice for predicting epidemics. Therefore, we used and validated a model based on Farr law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence. Methods: We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions. A model based on Farr law was developed using the data available on Feb. 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward. Results: We observed 50,995 (37001 on or before Feb. 8) incident cases in China from January 16 to February 15, 2020. The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes. If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city. However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend. The predicted trends overall match the prospectively-collected data, confirming usefulness of these models. Conclusions: This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing. However, there is a possibility of upward trend.", "qid": 25, "docid": "hpid3fzc", "rank": 67, "score": 9.375699996948242}, {"content": "Title: Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr's law Content: BACKGROUND: The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful Farr's law is a classic epidemiology theory/practice for predicting epidemics Therefore, we used and validated a model based on Farr's law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence METHODS: We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions A model based on Farr's law was developed using the data available on Feb 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward RESULTS: We observed 50,995 (37,001 on or before Feb 8) incident cases in China from January 16 to February 15, 2020 The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend The predicted trends overall match the prospectively-collected data, confirming usefulness of these models CONCLUSIONS: This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing However, there is a possibility of upward trend", "qid": 25, "docid": "smi9iy0p", "rank": 68, "score": 9.375699043273926}, {"content": "Title: Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr's law. Content: BACKGROUND The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China. Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful. Farr's law is a classic epidemiology theory/practice for predicting epidemics. Therefore, we used and validated a model based on Farr's law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence. METHODS We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions. A model based on Farr's law was developed using the data available on Feb. 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward. RESULTS We observed 50,995 (37,001 on or before Feb. 8) incident cases in China from January 16 to February 15, 2020. The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes. If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city. However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend. The predicted trends overall match the prospectively-collected data, confirming usefulness of these models. CONCLUSIONS This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing. However, there is a possibility of upward trend.", "qid": 25, "docid": "ylhfe5nc", "rank": 69, "score": 9.37569808959961}, {"content": "Title: D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19 Content: A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 \u00c5(3) on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easily to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.", "qid": 25, "docid": "gjpgcimx", "rank": 70, "score": 9.364399909973145}, {"content": "Title: Vaccine development and therapeutic design for 2019\u2010nCoV/SARS\u2010CoV\u20102: Challenges and chances Content: The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019\u2010nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019\u2010nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time\u2010consuming and expensive to obtain. Scientific simulations and more in\u2010depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti\u20102019\u2010nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019\u2010nCoV. Computational\u2010based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS\u2010CoV\u20102.", "qid": 25, "docid": "bsobuwl2", "rank": 71, "score": 9.321499824523926}, {"content": "Title: Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances Content: The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.", "qid": 25, "docid": "y5tts376", "rank": 72, "score": 9.32149887084961}, {"content": "Title: Neutrophil to CD4+ lymphocyte ratio as a potential biomarker in predicting virus negative conversion time in COVID-19 Content: BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. Our study aimed to evaluate the robustness of neutrophil to CD4+ lymphocyte ratio (NCD4LR) in predicting the negative conversion time (NCT) of SARS-CoV-2 in COVID-19 patients. METHODS: Univariate and multivariate analysis were conducted to evaluate the independency of NCD4LR in predicting NCT. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to assess the diagnostic accuracy. RESULTS: Compared with low NCD4LR patients, patients with high NCD4LR had an older age; higher incidence of fever, fatigue, chest distress/breath shortness, severer disease assessment on admission; higher levels of inflammatory indicators; low levels of lymphocyte subsets, and a longer NCT. Multivariate analysis also identified NCD4LR as an independent risk factor for delayed NCT. ROC analysis showed that NCD4LR had a better performance than neutrophil to lymphocyte ratio in predicting the virus negative conversion within 2 weeks (AUC = 0.772), 3 weeks (AUC = 0.710), 4 weeks (AUC = 0.728), or 5 weeks (AUC = 0.815). CONCLUSION: This study suggests that NCD4LR is a potential and useful biomarker for predicting the virus negative conversion time in COVID-19 patients. Furthermore, due to the NCDLR value is easily calculated, it can be widely used as a clinical biomarker for disease progression and clinical outcomes in COVID-19 patients.", "qid": 25, "docid": "dvpl8dfx", "rank": 73, "score": 9.319999694824219}, {"content": "Title: Global dynamics of a SUIR model with predicting COVID-19 Content: Since December 2019, A novel coronavirus (2019-nCoV) has been breaking out in China, which can cause respiratory diseases and severe pneumonia. Epidemic models relying on the incidence rate of new cases for forecasting epidemic outbreaks have received increasing attention. However, many prior works in this area mostly focus on the application of the traditional SIR model and disregard the transmission characteristics of 2019-nCoV, exceptionally the infectious of undiagnosed cases. Here, we propose a SUIR model based on the classical SIR model object to supervise the effective prediction, prevention, and control of infectious diseases. SUIR model adds a unique $U$ (Undiagnosed) state of the epidemic and divides the population into four states: S (Susceptible), U (Undiagnosed), I (Infectious and Uninfectious), and R (Recovered). This approach enables us to predict the incidence of 2019-nCoV effectively and the clear advantage of the model accuracy more reliable than the traditional SIR model.", "qid": 25, "docid": "kr1qy54q", "rank": 74, "score": 9.304400444030762}, {"content": "Title: An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov) Content: The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a na\u00efve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.", "qid": 25, "docid": "thu861hj", "rank": 75, "score": 9.290599822998047}, {"content": "Title: Novel coronavirus infection in children outside of Wuhan, China Content: BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.", "qid": 25, "docid": "nb8hpst0", "rank": 76, "score": 9.28600025177002}, {"content": "Title: Novel coronavirus infection in children outside of Wuhan, China Content: BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID\u201019) has spread rapidly, but information about children with COVID\u201019 is limited. METHODS: This retrospective and the single\u2010center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID\u201019 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019\u2010nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019\u2010nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground\u2010glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT\u2010PCR for 2019\u2010nCoV and were discharged. The median time from exposure to a negative RT\u2010PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.", "qid": 25, "docid": "txssq1p1", "rank": 77, "score": 9.285999298095703}, {"content": "Title: Neurophysiologic predictors of response to atomoxetine in young adults with attention deficit hyperactivity disorder: a pilot project. Content: Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) enrolled in a multi-site, double-blind placebo-controlled study of the effectiveness of atomoxetine and underwent serial qEEG recordings at pretreatment baseline and one week after the start of medication. qEEG measures were calculated from a subset of the sample (N = 29) that provided useable qEEG recordings. Left temporoparietal cordance in the theta frequency band after one week of treatment was associated with ADHD symptom improvement and quality of life measured at 12 weeks in atomoxetine-treated subjects, but not in those treated with placebo. Neither absolute nor relative power measures selectively predicted improvement in medication-treated subjects. Measuring theta cordance after one week of treatment could be useful in predicting atomoxetine treatment response in adult ADHD.", "qid": 25, "docid": "quacyyln", "rank": 78, "score": 9.280900001525879}, {"content": "Title: ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection Content: In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.", "qid": 25, "docid": "s5w8rf6t", "rank": 79, "score": 9.267900466918945}, {"content": "Title: Circulating microRNAs in malaria infection: bench to bedside Content: Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas. The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited. Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease. However, a few of these factors could be applied to clinical practice. MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases. Recently it was found that plasma miR-451 and miR-16 were downregulated in malaria infection at parasitic stages or with multi-organ failure involvement. MiR-125b, -27a, -23a, -150, 17\u201392 and -24 are deregulated in malaria patients with multiple organ failures. Here, the current findings of miRNAs were reviewed in relation to clinical severity of malaria infection and emphasized that miRNAs are potential biomarkers for severe malaria infection.", "qid": 25, "docid": "gse1k0wh", "rank": 80, "score": 9.262299537658691}, {"content": "Title: First Case of 2019 Novel Coronavirus in the United States Content: An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient\u2019s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.", "qid": 25, "docid": "7z7zxcm2", "rank": 81, "score": 9.253399848937988}, {"content": "Title: First Case of 2019 Novel Coronavirus in the United States Content: An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.", "qid": 25, "docid": "tt3pbpmu", "rank": 82, "score": 9.253398895263672}, {"content": "Title: A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults. Content: Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%) & 1 (4%), respectively. The median incubation period of children and adults was 5 days (range 3-12 days) and 4 days (range 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5, 71.4%) was roughly the same as adults (20, 80%). 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=0.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs. 4%, P=0.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019 novel coronavirus disease (COVID-19), but also for a future discussion on age-specific coronavirus infection. This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "4oocm6o1", "rank": 83, "score": 9.222100257873535}, {"content": "Title: Predictions for the binding domain and potential new drug targets of 2019-nCoV Content: An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.", "qid": 25, "docid": "fvig79k3", "rank": 84, "score": 9.212900161743164}, {"content": "Title: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity Content: The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002\u20132003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.", "qid": 25, "docid": "76vgv8qs", "rank": 85, "score": 9.188599586486816}, {"content": "Title: Hemostatic laboratory derangements in COVID-19 with a focus on platelet count. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.", "qid": 25, "docid": "4srdobgu", "rank": 86, "score": 9.183300018310547}, {"content": "Title: Hemostatic laboratory derangements in COVID-19 with a focus on platelet count Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.", "qid": 25, "docid": "nvs3kz78", "rank": 87, "score": 9.18329906463623}, {"content": "Title: In silico identification of vaccine targets for 2019-nCoV Content: Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.", "qid": 25, "docid": "23ryjycz", "rank": 88, "score": 9.179900169372559}, {"content": "Title: In silico identification of vaccine targets for 2019-nCoV. Content: Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.", "qid": 25, "docid": "z20po3eq", "rank": 89, "score": 9.179899215698242}, {"content": "Title: Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients Content: A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin\u2013angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO(2)/FiO(2) ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms4595) contains supplementary material, which is available to authorized users.", "qid": 25, "docid": "2vo80sry", "rank": 90, "score": 9.173399925231934}, {"content": "Title: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis Content: Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "qid": 25, "docid": "apgh3j3r", "rank": 91, "score": 9.145600318908691}, {"content": "Title: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Content: Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "qid": 25, "docid": "fg69m7o0", "rank": 92, "score": 9.145599365234375}, {"content": "Title: Predictive Data Mining Models for Novel Coronavirus (COVID-19) Infected Patients\u2019 Recovery Content: Novel coronavirus (COVID-19 or 2019-nCoV) pandemic has neither clinically proven vaccine nor drugs; however, its patients are recovering with the aid of antibiotic medications, anti-viral drugs, and chloroquine as well as vitamin C supplementation. It is now evident that the world needs a speedy and quicker solution to contain and tackle the further spread of COVID-19 across the world with the aid of non-clinical approaches such as data mining approaches, augmented intelligence and other artificial intelligence techniques so as to mitigate the huge burden on the healthcare system while providing the best possible means for patients' diagnosis and prognosis of the 2019-nCoV pandemic effectively. In this study, data mining models were developed for the prediction of COVID-19 infected patients\u2019 recovery using epidemiological dataset of COVID-19 patients of South Korea. The decision tree, support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor algorithms were applied directly on the dataset using python programming language to develop the models. The model predicted a minimum and maximum number of days for COVID-19 patients to recover from the virus, the age group of patients who are of high risk not to recover from the COVID-19 pandemic, those who are likely to recover and those who might be likely to recover quickly from COVID-19 pandemic. The results of the present study have shown that the model developed with decision tree data mining algorithm is more efficient to predict the possibility of recovery of the infected patients from COVID-19 pandemic with the overall accuracy of 99.85% which stands to be the best model developed among the models developed with other algorithms including support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor.", "qid": 25, "docid": "dvg0isgt", "rank": 93, "score": 9.135299682617188}, {"content": "Title: Gaining insight into SARS-CoV-2 infection and COVID-19 severity using self-supervised edge features and Graph Neural Networks Content: Graph Neural Networks (GNN) have been extensively used to extract meaningful representations from graph structured data and to perform predictive tasks such as node classification and link prediction. In recent years, there has been a lot of work incorporating edge features along with node features for prediction tasks. In this work, we present a framework for creating new edge features, via a combination of self-supervised and unsupervised learning which we then use along with node features for node classification tasks. We validate our work on two biological datasets comprising of single-cell RNA sequencing data of \\textit{in vitro} SARS-CoV-2 infection and human COVID-19 patients. We demonstrate that our method achieves better performance over baseline Graph Attention Network (GAT) and Graph Convolutional Network (GCN) models. Furthermore, given the attention mechanism on edge and node features, we are able to interpret the cell types and genes that determine the course and severity of COVID-19, contributing to a growing list of potential disease biomarkers and therapeutic targets.", "qid": 25, "docid": "8wb3384l", "rank": 94, "score": 9.120599746704102}, {"content": "Title: Early Prediction of the 2019 Novel Coronavirus Outbreak in the Mainland China Based on Simple Mathematical Model Content: The 2019 novel coronavirus (2019-nCoV) outbreak has been treated as a Public Health Emergency of International Concern by the World Health Organization. This work made an early prediction of the 2019-nCoV outbreak in China based on a simple mathematical model and limited epidemiological data. Combing characteristics of the historical epidemic, we found part of the released data is unreasonable. Through ruling out the unreasonable data, the model predictions exhibit that the number of the cumulative 2019-nCoV cases may reach 76,000 to 230,000, with a peak of the unrecovered infectives (22,000-74,000) occurring in late February to early March. After that, the infected cases will rapidly monotonically decrease until early May to late June, when the 2019-nCoV outbreak will fade out. Strong anti-epidemic measures may reduce the cumulative infected cases by 40%-49%. The improvement of medical care can also lead to about one-half transmission decrease and effectively shorten the duration of the 2019-nCoV.", "qid": 25, "docid": "vxfkb3jb", "rank": 95, "score": 9.116700172424316}, {"content": "Title: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity Content: The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002&ndash;2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins", "qid": 25, "docid": "h632ll6u", "rank": 96, "score": 9.114399909973145}, {"content": "Title: Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia Content: Background: The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019- nCoV infections in neonates. Methods: The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. Results: Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. Conclusions: Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.", "qid": 25, "docid": "jetjxf90", "rank": 97, "score": 9.10509967803955}, {"content": "Title: [The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease] Content: Objective: To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy. Methods: Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI. Results: Among the 139 cancer patients who underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized with GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man who was diagnosed with non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection, fever or other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed with viral pneumonia and an experiential anti-infection treatment had been prescribed for him. Conclusions: The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be taken into combined consideration. The 2019-nCoV nuclear acid testing might be applied in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.", "qid": 25, "docid": "fs7qsqn2", "rank": 98, "score": 9.062899589538574}, {"content": "Title: The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease/ \u4e2d\u534e\u80bf\u7624\u6742\u5fd7 Content: Objective@#To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy.@*Methods@#Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI.@*Results@#Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him.@*Conclusions@#The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.", "qid": 25, "docid": "s5f1olt4", "rank": 99, "score": 9.062898635864258}, {"content": "Title: [The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease]. Content: Objective: To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy. Methods: Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI. Results: Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him. Conclusions: The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.", "qid": 25, "docid": "yk8f9jtn", "rank": 100, "score": 9.062897682189941}]}
{"query": "what are the initial symptoms of Covid-19?", "hits": [{"content": "Title: Command Suicidal Hallucination as Initial Presentation of Coronavirus Disease 2019 (COVID-19): A Case Report Content: INTRODUCTION: Presently the COVID-19 pandemic is raging through the United States and worldwide. This enigmatic virus characteristically affects the respiratory system. Atypical presentations, such as gastrointestinal symptoms, and cases of encephalopathy have also been reported. However, psychiatric symptoms as the initial presenting feature is novel. We describe one such case. CASE PRESENTATION: 53-year-old man with no prior psychiatric or significant medical history was brought to the emergency department after ingesting bleach in an apparent suicide attempt. On initial presentation, the patient was uncooperative and withdrawn, though alert and oriented. He subsequently developed fever, tachycardia, elevated blood urea nitrogen and transaminases. SARS CoV-2 was confirmed on RT-PCR. Neurological examination was non-contributory. As his clinical condition improved, the patient reported that his initial symptom was an auditory hallucination telling him to jump from a bridge or ingest bleach. He reported that the increasing intensity of his auditory hallucinations led him to act upon it. He denied mood symptoms or suicidal ideation. The hallucinations did not recur during the hospital course, but he required 3 doses of antipsychotic medication for agitation. After improvement of his SARS CoV-2 infection, he was free of psychiatric symptoms and was discharged to a subacute rehabilitation center. CONCLUSION: This case indicates that what appears as a sudden onset of a psychiatric illness in the current context may be an initial manifestation of a developing COVID illness.", "qid": 26, "docid": "d3qgrjc4", "rank": 1, "score": 7.752900123596191}, {"content": "Title: Patients with specific skin disorders who are affected by COVID\u201019: what do experiences say about management strategies? : A systematic review Content: BACKGROUND AND AIM: In patients with dermatologic disorders who are affected by new corona virus, we know little about course (underlying disease and new onset\u2010infection) and the most proper management strategies include both issues that are what this systematic review targets. METHOD: Databases of PubMed, Scopus, Google Scholar, Medscape and CEBD coronavirus dermatology resource of Nottingham University searched completely and initial 237 articles selected to further review and finally nine articles (including 12 patients) entered to this study. RESULT: from 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only one patient required ICU admission, the others have been treated for mild\u2010 moderate symptoms with conventional therapies. The biologic or immunosuppressive/ Immunomodulator agents has been ceased during the course of disease. The course of COVID\u201019 its management was as similar as normal populations. Their underlying dermatologic disease was exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. CONCLUSION: Exacerbation of patients underlying dermatologic disease is mild\u2010 moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence in these patients. This article is protected by copyright. All rights reserved.", "qid": 26, "docid": "s5oxr6es", "rank": 2, "score": 7.0954999923706055}, {"content": "Title: Patients with specific skin disorders who are affected by COVID-19: What do experiences say about management strategies? A systematic review Content: In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection), and the most proper management strategies include both issues that are what this systematic review targets. Databases of PubMed, Scopus, Google Scholar, Medscape, and Centre of Evidence-Based Dermatology, coronavirus dermatology resource of Nottingham University searched completely up to May 15, 2020, and initial 237 articles were selected to further review and finally 9 articles (including 12 patients) entered to this study. From 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only 1 patient required Intensive Care Unit admission, the others have been treated for mild-moderate symptoms with conventional therapies. The biologic or immunosuppressive/immunomodulator agents have been ceased during the course of disease. The course of coronovirus diseases 2019 (COVID-19) and its management was as similar as normal populations. Their underlying dermatologic disease were exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. Exacerbation of patients underlying dermatologic disease was mild to moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence and disturbing cytokine storms in these patients.", "qid": 26, "docid": "x96vp6r4", "rank": 3, "score": 6.97730016708374}, {"content": "Title: Shedding Light on Dysphagia Associated With COVID-19: The What and Why Content: The most common symptom of COVID-19 in critically ill patients is ARDS (acute respiratory distress syndrome), with many patients requiring invasive or noninvasive respiratory support in the intensive care unit. Oropharyngeal dysphagia may be a consequence of the respiratory-swallowing incoordination common in ARDS or may occur following the respiratory support interventions. In this commentary, we highlight the risk and complications of oropharyngeal dysphagia in patients with COVID-19 and urge medical and rehabilitation professionals to consider dysphagia a prognostic complication, provide appropriate referrals, and initiate early interventions as appropriate.", "qid": 26, "docid": "sy7kgh2a", "rank": 4, "score": 6.89300012588501}, {"content": "Title: General Surgery Operating Room Practice in Patients with COVID-19 Content: The virus COVID-19, which emerged in China in December 2019, was announced by the World Health Organization as a pandemic in January 2020 It is known that infection is not severe and may even progress without symptoms in patients who have come into contact with COVID-19 Although various organizations have been informed about how to take measures to protect the patient and the surgeon in case of diseases requiring urgent or elective surgery in people infected with COVID-19 or in cases with high suspicion, there is still no definite judgment between patients, physicians and health authorities In this study, which was prepared with the initiative of the Turkish Surgical Association, we tried to shed light on what should be done and how surgeons should act in patients whose operation is mandatory in light of the available data", "qid": 26, "docid": "lsse2xvw", "rank": 5, "score": 6.7153000831604}, {"content": "Title: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement Content: With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.", "qid": 26, "docid": "5p0yyrdx", "rank": 6, "score": 6.709099769592285}, {"content": "Title: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement Content: [Image: see text] With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.", "qid": 26, "docid": "kbvy4g7i", "rank": 7, "score": 6.709098815917969}, {"content": "Title: Ophthalmic Manifestations Of Coronavirus (COVID-19) Content: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] There have been several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis may be an ocular manifestation of SARS-CoV-2 infection A study conducted during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak detected SARS-CoV in tear samples in SARS patients in Singapore [2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions [3][[4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19 As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19 Indeed, one of the first providers to voice concerns regarding the spread of Coronavirus in Chinese patients was Li Wenliang, MD, an ophthalmologist He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission", "qid": 26, "docid": "vzxutyii", "rank": 8, "score": 6.6234002113342285}, {"content": "Title: Rhabdomyolysis as a Presentation of 2019 Novel Coronavirus Disease Content: An emerging viral infection is a global public health challenge. The development of modern, fast, and extensive transportation makes the outbreak hard to contain. Everyone is at risk, and the outbreak can rapidly turn into a pandemic crisis, like what we are currently facing for the 2019 novel coronavirus disease (COVID-19). Prompt diagnosis of the case is required to improve patients\u2019 prognosis and control of the outbreak. The common manifestations of COVID-19 include fever, cough, dyspnea, and malaise. However, patients may present with atypical symptoms that pose a diagnostic challenge. We report the first case of an elderly male who presented with rhabdomyolysis and later was diagnosed with COVID-19. Clinicians should be aware that rhabdomyolysis can be an initial presentation of COVID-19 or can occur at any time during the disease course. Patients with rhabdomyolysis should receive aggressive fluid administration to prevent acute kidney injury (AKI). However, COVID-19 patients are at risk of worsening oxygenation and acute hypoxemic respiratory failure from fluid overload. Therefore, cautious fluid administration is needed in COVID-19 patients with rhabdomyolysis.", "qid": 26, "docid": "o3b2yvbs", "rank": 9, "score": 6.551799774169922}, {"content": "Title: Self-reported alteration of sense of smell or taste in patients with COVID-19: a systematic review and meta-analysis on 3563 patients Content: BACKGROUND: Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. METHODS: The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. RESULTS: 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. CONCLUSIONS: Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.", "qid": 26, "docid": "0cydu5cv", "rank": 10, "score": 6.404300212860107}, {"content": "Title: Self-reported alteration of sense of smell or taste in patients with COVID-19: a systematic review and meta-analysis on 3563 patients. Content: BACKGROUND Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. METHODS The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. RESULTS 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. CONCLUSIONS Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.", "qid": 26, "docid": "qilh19ai", "rank": 11, "score": 6.404299259185791}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 26, "docid": "gnaubzah", "rank": 12, "score": 6.388500213623047}, {"content": "Title: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Content: Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.", "qid": 26, "docid": "hlhhvmtu", "rank": 13, "score": 6.3884992599487305}, {"content": "Title: Case-Initiated COVID-19 Contact Tracing Using Anonymous Notifications Content: We discuss the concept of a participatory digital contact notification approach to assist tracing of contacts who are exposed to confirmed cases of coronavirus disease (COVID-19); the approach is simple and affordable for countries with limited access to health care resources and advanced technology. The proposed tool serves as a supplemental contract tracing approach to counteract the shortage of health care staff while providing privacy protection for both cases and contacts. This tool can be deployed on the internet or as a plugin for a smartphone app. Confirmed cases with COVID-19 can use this tool to provide contact information (either email addresses or mobile phone numbers) of close contacts. The system will then automatically send a message to the contacts informing them of their contact status, what this status means, the actions that should follow (eg, self-quarantine, respiratory hygiene/cough etiquette), and advice for receiving early care if they develop symptoms. The name of the sender of the notification message by email or mobile phone can be anonymous or not. The message received by the contact contains no disease information but contains a security code for the contact to log on the platform to retrieve the information.", "qid": 26, "docid": "qmp2h3h2", "rank": 14, "score": 6.335299968719482}, {"content": "Title: Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases Content: BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo-chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID-19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID-19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID-19, using a consensus method to define morphological patterns associated with COVID-19. We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition.", "qid": 26, "docid": "8r4no840", "rank": 15, "score": 6.28980016708374}, {"content": "Title: Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China Content: Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3\u201316 days), 7 with anorexia (7\u201322 days), 6 with upper abdominal discomfort (1\u20137 days), and 4 with nausea (1\u20137 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.", "qid": 26, "docid": "0fzwwluc", "rank": 16, "score": 6.282800197601318}, {"content": "Title: Psychological Impact and Associated Factors During the Initial Stage of the Coronavirus (COVID-19) Pandemic Among the General Population in Spain Content: The outbreak of COVID-19 in Spain started at the end of February. By 9th April 2020 Spain was the second country in confirmed cases and in deaths. On March 14, 2020, the Spanish Government declared the state of alarm to limit viral transmission. During such state, citizens must stay confined at home with few justified exceptions. This whole situation drastically changed the life of the population, which can cause a wide range of psychosocial impacts. This study explored the psychological impact of the COVID-19 pandemic in the general adult population (N = 3055) during the first stages of the outbreak in Spain, as well as their anxiety, stress and depression levels. We also examined the extent to which the following variables were associated to participants\u2019 mental health: (1) demographics; (2) degree of concern about the pandemic; (3) environmental conditions during the home confinement, (4) changes in daily life as a consequence of the pandemic; (5) contact with the COVID-19 disease; (6) actual and perceived severity of the crisis; (7) information about the COVID-19, (8) perceived health status and (9) leisure activities conducted within the last 24 h. Our results show that Spanish consider the current COVID-19 health crisis as fairly severe, and the majority felt that the COVID-19 crisis had greatly impacted on their daily life, including changes in their daily routines and cancelation of important activities. About 36% of the participants reported moderate to severe psychological impact, 25% showed mild to severe levels of anxiety, 41% reported depressive symptoms, and 41% felt stressed. Women, young, and those who that lost their job during the health crisis showed the strongest negative psychological symptoms. What worried Spaniards the most was the likelihood of suffering an economic crisis derived from the pandemic. We found factors associated with better mental health, such as being satisfied with the information received about the health crisis, conducting leisure activities, and the perception of being in good health. These findings can be used to design psychological interventions to help coping with COVID-19 pandemic, both in Spain and other countries.", "qid": 26, "docid": "7j98rhr8", "rank": 17, "score": 6.26200008392334}, {"content": "Title: One Academic Health System's Early (and Ongoing) Experience Responding to COVID-19: Recommendations From the Initial Epicenter of the Pandemic in the United States Content: On January 19, 2020, the first case of a patient with coronavirus disease 2019 (COVID-19) in the United States was reported in Washington State. On February 29, 2020, a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) passed away in a hospital in Seattle-King County, the first reported COVID-19-related death in the United States. That same day, a skilled nursing and rehabilitation facility in the county reported that several of its residents tested positive for SARS-CoV-2 and that many staff had symptoms compatible with COVID-19.The University of Washington Medicine health system (UW Medicine), which is based in Seattle-King County and provides quaternary care for the region, was one of several health care organizations called upon to address this growing crisis. What ensued was a series of swiftly enacted decisions and activities at UW Medicine, in partnership with local, state, and national public health agencies, to respond to the COVID-19 pandemic. Tapping into the multipronged mission areas of academic medicine, UW Medicine worked to support the community, innovate in science and clinical practice, lead policy and practice guideline development, and adopt changes as the crisis unfolded. In doing so, health system leaders had to balance their commitments to students, residents and fellows, researchers, faculty, staff, and hospital and health center entities, while ensuring that patients continued to receive cutting edge, high-quality, safe care. In this Invited Commentary, the authors highlight the work and challenges UW Medicine has faced in responding to the global COVID-19 pandemic.", "qid": 26, "docid": "jw85ao93", "rank": 18, "score": 6.1539998054504395}, {"content": "Title: One Academic Health System\u2019s Early (and Ongoing) Experience Responding to COVID-19: Recommendations From the Initial Epicenter of the Pandemic in the United States Content: On January 19, 2020, the first case of a patient with coronavirus disease 2019 (COVID-19) in the United States was reported in Washington State. On February 29, 2020, a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) passed away in a hospital in Seattle-King County, the first reported COVID-19-related death in the United States. That same day, a skilled nursing and rehabilitation facility in the county reported that several of its residents tested positive for SARS-CoV-2 and that many staff had symptoms compatible with COVID-19. The University of Washington Medicine health system (UW Medicine), which is based in Seattle-King County and provides quaternary care for the region, was one of several health care organizations called upon to address this growing crisis. What ensued was a series of swiftly enacted decisions and activities at UW Medicine, in partnership with local, state, and national public health agencies, to respond to the COVID-19 pandemic. Tapping into the multipronged mission areas of academic medicine, UW Medicine worked to support the community, innovate in science and clinical practice; lead policy and practice guideline development; and adopt changes as the crisis unfolded. In doing so, health system leaders had to balance their commitments to students, residents and fellows, researchers, faculty, staff, and hospital and health center entities, while ensuring that patients continued to receive cutting-edge, high-quality, safe care. In this Invited Commentary, the authors highlight the work and challenges UW Medicine has faced in responding to the global COVID-19 pandemic.", "qid": 26, "docid": "mhwqgjbg", "rank": 19, "score": 6.153998851776123}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10\u201320% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 26, "docid": "2ootfjhk", "rank": 20, "score": 6.149899959564209}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 26, "docid": "88n6hwyo", "rank": 21, "score": 6.149899005889893}, {"content": "Title: A First Look at Contact Tracing Apps Content: Today's smartphones come with a large number of powerful additional devices such as a low power Bluetooth sensor, powerful embedded sensors such as the digital compass, accelerometer, GPS sensors, Wi-Fi capabilities, microphone, humidity sensors, health tracking sensors, and camera. These value-added sensors revolutionize many sectors of today's community including tracking, social networking, healthcare, manufacturing, and monitoring of the environment, etc. These additional embedded sensors could be used for large-scale personal, group, and community sensing applications. Governments and regulators are turning to use these features of the smartphone technology to trace the people thought to have symptoms of certain diseases or virus e.g. COVID-19. The outbreak of COVID-19 in December 2019, has seen a surge of the mobile applications for tracing, tracking and isolating the persons showing COVID-19 symptoms in-order to overcome the contagious disease. As the embedded sensors could disclose private information of the users thus potentially bring threat to the privacy and security of users. In this paper, we analyzed a large set of smartphone applications that have been designed by the governments to deal with the COVID-19 outbreak and bring the people back to normal life. Specifically, we analyzed what type of permission these smartphone apps require, whether these permissions are necessary for the track and trace, how data from the user devices is transported to the analytics center, what security measures apps have deployed, and what privacy threats these features could have.", "qid": 26, "docid": "5mwhc6q7", "rank": 22, "score": 6.127699851989746}, {"content": "Title: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say? Content: There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.", "qid": 26, "docid": "zpb9jicw", "rank": 23, "score": 6.071400165557861}, {"content": "Title: A Critical Needs Assessment for Research in Companion Animals and Livestock Following the Pandemic of COVID-19 in Humans Content: Problem: The emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China, in November 2019 and a growing body of information compel inquiry regarding the transmissibility of infection between humans and certain animal species. Although there are a number of issues to be considered, the following points are most urgent: The potential for domesticated (companion) animals to serve as a reservoir of infection contributing to continued human-to-human disease, infectivity, and community spread. The ramifications to food security, economy, and trade issues should coronavirus establish itself within livestock and poultry. The disruption to national security if SARS-CoV-2 and its fairly well-established effects on smell (hyposmia/anosmia) to critical military service animals including explosive detector dog, narcotics detector dog, specialized search dog, combat tracker dog, mine detection dog, tactical explosive detector dog, improvised explosive device detector dog, patrol explosive detector dog, and patrol narcotics detector dog, as well as multipurpose canines used by special operations such as used by the U.S. customs and border protection agency (e.g., Beagle Brigade). This article presents in chronological order data that both individually (as received independently from multiple countries) and collectively urge studies that elucidate the following questions. 1.What animal species can be infected with SARS-CoV-2, the likely sources of infection, the period of infectivity, and transmissibility between these animals and to other animal species and humans? 2.What are the best diagnostic tests currently available for companion animals and livestock? 3.What expressions of illness in companion and other animal species can serve as disease markers? Although it is recognized that robust funding and methodology need to be identified to apply the best scientific investigation into these issues, there may be easily identifiable opportunities to capture information that can guide decision and study. First, it may be possible to quickly initiate a data collection strategy using in-place animal gatekeepers, such as zookeepers, veterinarians, kennel owners, feed lots, and military animal handlers. If provided a simple surveillance form, their detection of symptoms (lethargy, hyposmia, anosmia, and others) might be quickly reported to a central data collection site if one were created. Second, although current human COVID-19 disease is aligning around areas of population density and cluster events, it might be possible to overlay animal species density or veterinary reports that could signal some disease association in animals with COVID-19 patients. Unfortunately, although companion animals and zoo species have repeatedly served as sentinels for emerging infectious diseases, they do not currently fall under the jurisdiction of any federal agency and are not under surveillance.", "qid": 26, "docid": "cydhg0jz", "rank": 24, "score": 6.057600021362305}, {"content": "Title: A Critical Needs Assessment for Research in Companion Animals and Livestock Following the Pandemic of COVID-19 in Humans. Content: Problem: The emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China, in November 2019 and a growing body of information compel inquiry regarding the transmissibility of infection between humans and certain animal species. Although there are a number of issues to be considered, the following points are most urgent: The potential for domesticated (companion) animals to serve as a reservoir of infection contributing to continued human-to-human disease, infectivity, and community spread. The ramifications to food security, economy, and trade issues should coronavirus establish itself within livestock and poultry. The disruption to national security if SARS-CoV-2 and its fairly well-established effects on smell (hyposmia/anosmia) to critical military service animals including explosive detector dog, narcotics detector dog, specialized search dog, combat tracker dog, mine detection dog, tactical explosive detector dog, improvised explosive device detector dog, patrol explosive detector dog, and patrol narcotics detector dog, as well as multipurpose canines used by special operations such as used by the U.S. customs and border protection agency (e.g., Beagle Brigade). This article presents in chronological order data that both individually (as received independently from multiple countries) and collectively urge studies that elucidate the following questions. 1.What animal species can be infected with SARS-CoV-2, the likely sources of infection, the period of infectivity, and transmissibility between these animals and to other animal species and humans? 2.What are the best diagnostic tests currently available for companion animals and livestock? 3.What expressions of illness in companion and other animal species can serve as disease markers? Although it is recognized that robust funding and methodology need to be identified to apply the best scientific investigation into these issues, there may be easily identifiable opportunities to capture information that can guide decision and study. First, it may be possible to quickly initiate a data collection strategy using in-place animal gatekeepers, such as zookeepers, veterinarians, kennel owners, feed lots, and military animal handlers. If provided a simple surveillance form, their detection of symptoms (lethargy, hyposmia, anosmia, and others) might be quickly reported to a central data collection site if one were created. Second, although current human COVID-19 disease is aligning around areas of population density and cluster events, it might be possible to overlay animal species density or veterinary reports that could signal some disease association in animals with COVID-19 patients. Unfortunately, although companion animals and zoo species have repeatedly served as sentinels for emerging infectious diseases, they do not currently fall under the jurisdiction of any federal agency and are not under surveillance.", "qid": 26, "docid": "nooo6ttz", "rank": 25, "score": 6.057599067687988}, {"content": "Title: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts Content: BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R0 of 1\u00b75, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2\u00b75 or 3\u00b75 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1\u00b75 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2\u00b75 more than 70% of contacts had to be traced, and for an R0 of 3\u00b75 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1\u00b75. For R0 values of 2\u00b75 or 3\u00b75, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.", "qid": 26, "docid": "ofijw6n7", "rank": 26, "score": 6.027699947357178}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 26, "docid": "x82yaoxc", "rank": 27, "score": 6.013700008392334}, {"content": "Title: A case of COVID-19 patient with the diarrhea as initial symptom and literature review Content: Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.", "qid": 26, "docid": "0ylislv9", "rank": 28, "score": 6.008900165557861}, {"content": "Title: A case of COVID-19 patient with the diarrhea as initial symptom and literature review Content: Summary Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.", "qid": 26, "docid": "1aqtqaod", "rank": 29, "score": 6.008899211883545}, {"content": "Title: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis Content: OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.", "qid": 26, "docid": "epk4uksu", "rank": 30, "score": 5.990900039672852}, {"content": "Title: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms\u2014A Potential Pathway to Early Diagnosis Content: OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.", "qid": 26, "docid": "zv45usvu", "rank": 31, "score": 5.990899085998535}, {"content": "Title: What might the future bring? COVID-19 planning considerations for faculty and universities Content: This paper applies a scenario planning approach, to outline some current uncertainties related to COVID-19 and what they might mean for plausible futures for which we should prepare, and to identify factors that we as individual faculty members and university institutions should be considering now, when planning for the future under COVID-19. Although the contextual focus of this paper is Canada, the content is likely applicable to other places where the COVID-19 epidemic curve is in its initial rising stage, and where universities are predominantly publicly funded institutions.", "qid": 26, "docid": "mhnm4zac", "rank": 32, "score": 5.98859977722168}, {"content": "Title: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts Content: BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1\u00b75, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2\u00b75 or 3\u00b75 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1\u00b75 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2\u00b75 more than 70% of contacts had to be traced, and for an R(0) of 3\u00b75 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1\u00b75. For R(0) values of 2\u00b75 or 3\u00b75, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.", "qid": 26, "docid": "ueb7mjnv", "rank": 33, "score": 5.950799942016602}, {"content": "Title: What is the people posting about symptoms related to Coronavirus in Bogota, Colombia? Content: During the last months, there is an increasing alarm about a new mutation of coronavirus, covid-19 coined by World Health Organization(WHO) with an impact in many areas: economy, health, politics and others. This situation was declared a pandemic by WHO, because of the fast expansion over many countries. At the same time, people is using Social Networks to express what they think, feel or experiment, so this people are Social Sensors and helps to analyze what is happening in their city. The objective of this paper is analyze the publications of Colombian people living in Bogota with a radius of 50 km using Text Mining techniques from symptomatology approach. The results support the understanding of the spread in Colombia related to symptoms of covid19.", "qid": 26, "docid": "6jiy0b55", "rank": 34, "score": 5.935299873352051}, {"content": "Title: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Content: OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.", "qid": 26, "docid": "g7dhmyyo", "rank": 35, "score": 5.921999931335449}, {"content": "Title: Neurological manifestations of COVID-19: a review of what we know so far Content: Coronavirus disease 2019 (COVID\u201019) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.", "qid": 26, "docid": "blkhfhe2", "rank": 36, "score": 5.907599925994873}, {"content": "Title: Neurological manifestations of COVID-19: a review of what we know so far Content: Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.", "qid": 26, "docid": "rvo73h2l", "rank": 37, "score": 5.907598972320557}, {"content": "Title: A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID-19 Content: OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), manifests with a wide spectrum of presentations. Most reports of COVID-19 highlight fever and upper respiratory symptoms as the dominant initial presentations, consistent with the World Health Organization guidelines regarding suspected SARS-CoV-2 infection. However, atypical presentations of this disease have been evolving since the initial outbreak of the pandemic in December 2019. We report a case of an older male patient who presented at our hospital with an unusual manifestation of COVID-19. DESIGN: Brief report. SETTING: A university hospital in Saudi Arabia. PARTICIPANT: A 73-year-old man who presented with confusion in the absence of any respiratory symptoms or fever. INTERVENTION: The patient was initially admitted with delirium and underwent a further work-up. MEASUREMENTS: Given his recent history of domestic travel and the declaration of a global COVID-19 pandemic status, the patient was administered a swab test for SARS-CoV-2. RESULTS: The patient's positive test led to a diagnosis of COVID-19. Although he began to experience a spiking fever and mild upper respiratory symptoms, he recovered rapidly with no residual sequela. CONCLUSION: The recognition of atypical presentations of COVID-19 infection, such as delirium, is critical to the timely diagnosis, provision of appropriate care, and avoidance of outbreaks within healthcare facilities during this pandemic. J Am Geriatr Soc 68:1382-1384, 2020.", "qid": 26, "docid": "jeaqqbna", "rank": 38, "score": 5.878799915313721}, {"content": "Title: A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID\u201019 Content: OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), which causes coronavirus disease 2019 (COVID\u201019), manifests with a wide spectrum of presentations. Most reports of COVID\u201019 highlight fever and upper respiratory symptoms as the dominant initial presentations, consistent with the World Health Organization guidelines regarding suspected SARS\u2010CoV\u20102 infection. However, atypical presentations of this disease have been evolving since the initial outbreak of the pandemic in December 2019. We report a case of an older male patient who presented at our hospital with an unusual manifestation of COVID\u201019. DESIGN: Brief report. SETTING: A university hospital in Saudi Arabia. PARTICIPANT: A 73\u2010year\u2010old man who presented with confusion in the absence of any respiratory symptoms or fever. INTERVENTION: The patient was initially admitted with delirium and underwent a further work\u2010up. MEASUREMENTS: Given his recent history of domestic travel and the declaration of a global COVID\u201019 pandemic status, the patient was administered a swab test for SARS\u2010CoV\u20102. RESULTS: The patient's positive test led to a diagnosis of COVID\u201019. Although he began to experience a spiking fever and mild upper respiratory symptoms, he recovered rapidly with no residual sequela. CONCLUSION: The recognition of atypical presentations of COVID\u201019 infection, such as delirium, is critical to the timely diagnosis, provision of appropriate care, and avoidance of outbreaks within healthcare facilities during this pandemic.", "qid": 26, "docid": "nq466fvh", "rank": 39, "score": 5.878798961639404}, {"content": "Title: Ocular manifestations and clinical characteristics of 535 cases of COVID\u201019 in Wuhan, China: a cross\u2010sectional study Content: PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID\u201019 patients caused by SARS\u2010CoV\u20102 in Wuhan, China. METHODS: A total of 535 COVID\u201019 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS\u2010CoV\u20102 detection in nasopharyngeal swabs by real\u2010time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 \u00b1 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand\u2013eye contact was independently correlated with conjunctival congestion in COVID\u201019 patients. We also found that some COVID\u201019 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS\u2010CoV\u20102 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID\u201019\u2010related ocular symptoms, which could occur as the initial symptoms. Frequent hand\u2013eye contact may be the risk factor for conjunctival congestion in COVID\u201019 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID\u201019. It is essential to provide eye\u2010care equipment and strengthen education on eye protection.", "qid": 26, "docid": "bfp6tsuc", "rank": 40, "score": 5.865799903869629}, {"content": "Title: Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study Content: PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID-19 patients caused by SARS-CoV-2 in Wuhan, China. METHODS: A total of 535 COVID-19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS-CoV-2 detection in nasopharyngeal swabs by real-time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 \u00b1 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand-eye contact was independently correlated with conjunctival congestion in COVID-19 patients. We also found that some COVID-19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS-CoV-2 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID-19-related ocular symptoms, which could occur as the initial symptoms. Frequent hand-eye contact may be the risk factor for conjunctival congestion in COVID-19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID-19. It is essential to provide eye-care equipment and strengthen education on eye protection.", "qid": 26, "docid": "gexdgyfv", "rank": 41, "score": 5.8657989501953125}, {"content": "Title: First COVID-19 infections in the Philippines: a case report Content: BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient\u2019s condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.", "qid": 26, "docid": "ajbypz7g", "rank": 42, "score": 5.853600025177002}, {"content": "Title: Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment Content: Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.", "qid": 26, "docid": "6xph6ya7", "rank": 43, "score": 5.839300155639648}, {"content": "Title: Development of child immunity in the context of COVID-19 pandemic Content: Children, because of having an immature immune system, are usually more prone than the adults to the microbial infections and have more severe symptoms, which is especially true for the newborns, and very young children. However, the review of clinical data from the current COVID-19 pandemic indicates otherwise. We discuss here what are the main features and components of children's immune system, the role of maternal transmission of immunity, and what are the possible explanations for the seemingly lower infection rate and severity of COVI-19 in children.", "qid": 26, "docid": "p8aztarb", "rank": 44, "score": 5.821499824523926}, {"content": "Title: Hypogeusia as the initial presenting symptom of COVID-19 Content: COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory involvement. After 4 days in the ICU and 6 days on the general medicine floor, our patient regained a majority of her sense of smell and was discharged with only lingering dysgeusia. In this paper, we review existing literature and the clinical course of SARS-CoV-2 in relation to the reported symptoms of hyposmia, hypogeusia and dysgeusia.", "qid": 26, "docid": "z5u32l0w", "rank": 45, "score": 5.817299842834473}, {"content": "Title: Initial CT imaging characters of an imported family cluster of COVID-19 Content: The objective of this report is to better understand the initial CT imaging spectrum and the relationship between clinical characteristics and initial CT imaging features of an imported family cluster cases involving 7 laboratory-confirmed COVID-19 patients. We find that initial CT findings of 4 patients were positive within one week after the onset of symptoms and 1 patient was negative before the onset of symptoms. Two asymptomatic patients had typical CT abnormalities. The initial CT imaging manifestations are mainly peripheral or subpleural ground-glass opacities and ground-glass with consolidation. Our report is of potential guiding value for the initial CT screening of imported familial cluster cases since the imported cases have an identified time of infection.", "qid": 26, "docid": "aimvn68x", "rank": 46, "score": 5.814799785614014}, {"content": "Title: Initial CT imaging characters of an imported family cluster of COVID-19 Content: Abstract The objective of this report is to better understand the initial CT imaging spectrum and the relationship between clinical characteristics and initial CT imaging features of an imported family cluster cases involving 7 laboratory-confirmed COVID-19 patients. We find that initial CT findings of 4 patients were positive within one week after the onset of symptoms and 1 patient was negative before the onset of symptoms. Two asymptomatic patients had typical CT abnormalities. The initial CT imaging manifestations are mainly peripheral or subpleural ground-glass opacities and ground-glass with consolidation. Our report is of potential guiding value for the initial CT screening of imported familial cluster cases since the imported cases have an identified time of infection.", "qid": 26, "docid": "z7lz9syq", "rank": 47, "score": 5.814798831939697}, {"content": "Title: Delayed Initiation of Remdesivir in a COVID-19-Positive Patient Content: We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40-year-old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID-19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID-19 polymerase chain reaction result. Supportive measures, in addition to a 5-day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS-CoV-2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS-CoV-2 as well as to meet manufacturing demands.", "qid": 26, "docid": "jql4n0td", "rank": 48, "score": 5.810200214385986}, {"content": "Title: Delayed Initiation of Remdesivir in a COVID\u201019\u2010Positive Patient Content: We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40\u2010year\u2010old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID\u201019) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID\u201019 polymerase chain reaction result. Supportive measures, in addition to a 5\u2010day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS\u2010CoV\u20102, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS\u2010CoV\u20102 as well as to meet manufacturing demands.", "qid": 26, "docid": "ssuao9mb", "rank": 49, "score": 5.81019926071167}, {"content": "Title: Incidentally discovered COVID-19 in low-suspicion patients-a threat to front line health care workers Content: PURPOSE: The COVID-19 pandemic has been responsible for thousands of deaths worldwide. Testing remains at a premium, and criteria for testing remains reserved for those with lower respiratory infection symptoms and/or a known high-risk exposure. The role of imaging in COVID-19 is rapidly evolving; however, few algorithms include imaging criteria, and it is unclear what should be done in low-suspicion patients with positive imaging findings. METHODS: From 03/01/2020-03/20/2020, a retrospective review of all patients with suspected COVID-19 on imaging was performed. Imaging was interpreted by a board-certified, fellowship-trained radiologist. Patients were excluded if COVID-19 infection was suspected at the time of presentation, was the reason for imaging, or if any lower respiratory symptoms were present. RESULTS: Eight patients with suspected COVID-19 infection on imaging were encountered. Seven patients received testing due to suspicious imaging findings with subsequent lab-confirmed COVID-19. No patients endorsed prior exposure to COVID-19 or recent international travel. COVID-19 was suggested in six patients incidentally on abdominal CT and two on chest radiography. At the time of presentation, no patients were febrile, and seven endorsed gastrointestinal symptoms. Five COVID-19 patients eventually developed respiratory symptoms and required intubation. Two patients expired during the admission. CONCLUSIONS: Patients with imaging findings suspicious for COVID-19 warrant prompt reverse transcription polymerase chain reaction (RT-PCR) testing even in low clinical suspicion cases. The prevalence of disease in the population may be underestimated by the current paradigm of RT-PCR testing with the current clinical criteria of lower respiratory symptoms and exposure risk.", "qid": 26, "docid": "dhfl8qr5", "rank": 50, "score": 5.794600009918213}, {"content": "Title: Incidentally discovered COVID-19 in low-suspicion patients\u2014a threat to front line health care workers Content: PURPOSE: The COVID-19 pandemic has been responsible for thousands of deaths worldwide. Testing remains at a premium, and criteria for testing remains reserved for those with lower respiratory infection symptoms and/or a known high-risk exposure. The role of imaging in COVID-19 is rapidly evolving; however, few algorithms include imaging criteria, and it is unclear what should be done in low-suspicion patients with positive imaging findings. METHODS: From 03/01/2020\u201303/20/2020, a retrospective review of all patients with suspected COVID-19 on imaging was performed. Imaging was interpreted by a board-certified, fellowship-trained radiologist. Patients were excluded if COVID-19 infection was suspected at the time of presentation, was the reason for imaging, or if any lower respiratory symptoms were present. RESULTS: Eight patients with suspected COVID-19 infection on imaging were encountered. Seven patients received testing due to suspicious imaging findings with subsequent lab-confirmed COVID-19. No patients endorsed prior exposure to COVID-19 or recent international travel. COVID-19 was suggested in six patients incidentally on abdominal CT and two on chest radiography. At the time of presentation, no patients were febrile, and seven endorsed gastrointestinal symptoms. Five COVID-19 patients eventually developed respiratory symptoms and required intubation. Two patients expired during the admission. CONCLUSIONS: Patients with imaging findings suspicious for COVID-19 warrant prompt reverse transcription polymerase chain reaction (RT-PCR) testing even in low clinical suspicion cases. The prevalence of disease in the population may be underestimated by the current paradigm of RT-PCR testing with the current clinical criteria of lower respiratory symptoms and exposure risk.", "qid": 26, "docid": "x81035za", "rank": 51, "score": 5.7945990562438965}, {"content": "Title: Adapting to the COVID-19 pandemic in New York City Content: COVID-19 has and continues to overwhelm the medical establishment in New York City It has moved faster and had rates of mortality higher than what were initially forecast All departments within large hospital systems have had to learn lessons and adapt in real time to the crisis We share our experience and what we have learned as it pertains to this pandemic and hope that it aides, guides and influences other departments of physical medicine and rehabilitation regarding their potential roles and areas of growth during this time", "qid": 26, "docid": "a09ptyke", "rank": 52, "score": 5.772299766540527}, {"content": "Title: Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China Content: Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20\u201324 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p < 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p < 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.", "qid": 26, "docid": "d3owtd98", "rank": 53, "score": 5.767199993133545}, {"content": "Title: Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China Content: Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20-24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p < 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p < 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.", "qid": 26, "docid": "qujbaiq2", "rank": 54, "score": 5.7671990394592285}, {"content": "Title: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Content: Coronavirus disease-2019 (COVID-19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1-2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.", "qid": 26, "docid": "y5ptscri", "rank": 55, "score": 5.766300201416016}, {"content": "Title: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Content: Coronavirus disease-2019 (COVID\u201019) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1\u20132 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.", "qid": 26, "docid": "ywsm11aw", "rank": 56, "score": 5.766299247741699}, {"content": "Title: Prolonged SARS\u2010CoV\u20102 shedding and mild course of COVID\u201019 in a patient after recent heart transplantation Content: In the coronavirus disease 2019 (COVID\u201019) pandemic, organ transplant recipients are considered to be at high risk for unfavorable outcome. However, in particular the role of immunosuppression in patients infected with SARS\u2010CoV\u20102 remains undetermined. Here, we present a 62\u2010year old male COVID\u201019 patient with recent heart transplantation who developed only mild symptoms, but had prolonged virus shedding, and summarize the available data on COVID\u201019 in cardiac allograft recipients. Initially the patient presented with a transient episode of fever and sore throat but no other symptoms, in particular no cough or dyspnea at rest. After diagnosis, immunosuppression was continued unchanged. On day 7, temperature increased again with concurrent mild rise of CRP, IL\u20106 and proBNP levels. Hydroxychloroquine was started and continued for 7 days. While the patient had no clinical symptoms anymore 20 days after initial presentation, virus culture of throat swabs on days 18 and 21 confirmed active virus replication and SARS\u2010CoV\u20102 PCR remained positive on day 35 with copy numbers similar to the onset of infection. In conclusion, immunosuppression regimen in transplant recipients with mild COVID\u201019 associated symptoms may be continued unchanged. However, it may contribute to delayed virus PCR conversion and thus possible prolonged infectivity.", "qid": 26, "docid": "5867bc6i", "rank": 57, "score": 5.753200054168701}, {"content": "Title: Social innovation and food provisioning during Covid-19: The case of urban-rural initiatives in the Province Of Naples Content: This paper draws on the theoretical framework based on social innovation determinants to analyze how and to what extent the recent and self-organized initiatives for food provisioning are contributing to increase food accessibility at the time of personal and mobility restrictions due to Covid-19. Based on this, the paper firstly maps the initiatives activated during the first months of the Covid-19 emergency (March and April 2020) in the urban-rural territories in the province of Naples (Italy). Secondly, it characterizes these initiatives in relation to their capacity to enhance outcome and social well-being, as well as to involve local society in answer to social challenges through a desk research. Thirdly, the paper describes the case of Masseria Ferraioli, which emerges as social innovative best practice among the previous mapped initiatives. Even in these days, the Masseria distributes to people who cannot afford the purchase due to the emergency vegetables grown on land confiscated from the Camorra, the local mafia. Its configuration as social innovative experience is also confirmed directly by the Masserias project manager, who was required to answer to a semi-structured interview. Based on the evidence of the desk research and this interview, the paper demonstrates the importance of the combined commitment of local communities and volunteering association as a reaction to food provisioning problems in the time of Covid-19, as well as an increasing interest in reconnecting with local food practices, above all when food access has become a priority.", "qid": 26, "docid": "568domkf", "rank": 58, "score": 5.746200084686279}, {"content": "Title: Factors Associated with Depression, Anxiety, and PTSD Symptomatology During the COVID-19 Pandemic: Clinical Implications for U.S. Young Adult Mental Health Content: This study sought to identify factors associated with depression, anxiety, and PTSD symptomatology in U.S. young adults (18-30 years) during the COVID-19 pandemic. This cross-sectional online study assessed 898 participants from April 13, 2020 to May 19, 2020, approximately one month after the U.S. declared a state of emergency due to COVID-19 and prior to the initial lifting of restrictions across 50 U.S. states. Respondents reported high levels of depression (43.3%, PHQ-8 scores \u2265 10), high anxiety scores (45.4%, GAD-7 scores \u2265 10), and high levels of PTSD symptoms (31.8%, PCL-C scores \u2265 45). High levels of loneliness, high levels of COVID-19-specific worries, and low distress tolerance were significantly associated with clinical levels of depression, anxiety, and PTSD symptoms. Resilience was associated with low levels of depression and anxiety symptoms but not PTSD. Most respondents had high levels of social support; social support from family, but not from partner or peers, was associated with low levels of depression and PTSD. Compared to Whites, Asian Americans were less likely to report high levels across mental health symptoms, and Hispanic/Latinos were less likely to report high levels of anxiety. These factors provide initial guidance regarding clinical management for COVID-19-related mental health problems.", "qid": 26, "docid": "2mvcyvbl", "rank": 59, "score": 5.71589994430542}, {"content": "Title: Factors associated with depression, anxiety, and PTSD symptomatology during the COVID-19 pandemic: Clinical implications for U.S. young adult mental health Content: This study sought to identify factors associated with depression, anxiety, and PTSD symptomatology in U.S. young adults (18-30 years) during the COVID-19 pandemic. This cross-sectional online study assessed 898 participants from April 13, 2020 to May 19, 2020, approximately one month after the U.S. declared a state of emergency due to COVID-19 and prior to the initial lifting of restrictions across 50 U.S. states. Respondents reported high levels of depression (43.3%, PHQ-8 scores &#8805; 10), high anxiety scores (45.4%, GAD-7 scores &#8805; 10), and high levels of PTSD symptoms (31.8%, PCL-C scores &#8805; 45). High levels of loneliness, high levels of COVID-19-specific worry, and low distress tolerance were significantly associated with clinical levels of depression, anxiety, and PTSD symptoms. Resilience was associated with low levels of depression and anxiety symptoms but not PTSD. Most respondents had high levels of social support; social support from family, but not from partner or peers, was associated with low levels of depression and PTSD. Compared to Whites, Asian Americans were less likely to report high levels across mental health symptoms, and Hispanic/Latinos were less likely to report high levels of anxiety. These factors provide initial guidance regarding the clinical management for COVID-19-related mental health problems.", "qid": 26, "docid": "xl9ia23n", "rank": 60, "score": 5.7158989906311035}, {"content": "Title: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? Content: Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient\u2019s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "dnv2xl0h", "rank": 61, "score": 5.714200019836426}, {"content": "Title: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? Content: The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported. At first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms mainly include anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive presentations, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images consistent with COVID-19 infection. No data exist on the value of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "pbqm2xrg", "rank": 62, "score": 5.714199066162109}, {"content": "Title: Que doivent savoir les chirurgiens \u00e0 propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19?/ [What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?] Content: The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "sk5eugor", "rank": 63, "score": 5.6981000900268555}, {"content": "Title: Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients. Content: Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.", "qid": 26, "docid": "8e8h7bo3", "rank": 64, "score": 5.69189977645874}, {"content": "Title: Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation Content: In the coronavirus disease 2019 (COVID-19) pandemic, organ transplant recipients are considered to be at high risk for an unfavorable outcome. However, in particular the role of immunosuppression in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains undetermined. Here, we present a 62-year-old male COVID-19 patient with recent heart transplantation who developed only mild symptoms, but had prolonged virus shedding, and summarize the available data on COVID-19 in cardiac allograft recipients. Initially the patient presented with a transient episode of fever and sore throat but no other symptoms, in particular no cough or dyspnea at rest. After diagnosis, immunosuppression was continued unchanged. On day 7, his temperature increased again with concurrent mild rise of C-reactive protein, IL-6, and pro-B-type natriuretic peptide levels. Hydroxychloroquine was started and continued for 7 days. While the patient no longer had clinical symptoms 20 days after initial presentation, virus culture of throat swabs on days 18 and 21 confirmed active virus replication and SARS-CoV-2 PCR remained positive on day 35 with copy numbers similar to the onset of infection. In conclusion, the immunosuppression regimen in transplant recipients with mild COVID-19-associated symptoms may be continued unchanged. However, it may contribute to delayed virus polymerase chain reaction conversion and thus possible prolonged infectivity.", "qid": 26, "docid": "tqb41unj", "rank": 65, "score": 5.690400123596191}, {"content": "Title: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Content: Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any \u201dnormal\u201d post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.", "qid": 26, "docid": "iwkuwnun", "rank": 66, "score": 5.679699897766113}, {"content": "Title: COVID-19 is a Real Headache! Content: After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.", "qid": 26, "docid": "mqp3pjx6", "rank": 67, "score": 5.67609977722168}, {"content": "Title: COVID\u201019 is a Real Headache! Content: After the emergence of a novel coronavirus named SARS\u2010CoV\u20102, coronavirus disease 2019 (COVID\u201019) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID\u201019 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%\u201034% of the hospitalized COVID\u201019 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID\u201019 patients were new\u2010onset, moderate\u2010severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID\u201019. Symptomatic COVID\u201019 patients, around 6%\u201010%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS\u2010CoV\u20102 directly or through the vasculopathy and/or increased circulating pro\u2010inflammatory cytokines and hypoxia. We concluded that as a common non\u2010respiratory symptom of COVID\u201019, headache should not be overlooked, and its characteristics should be recorded with scrutiny.", "qid": 26, "docid": "q7r2vfo1", "rank": 68, "score": 5.676098823547363}, {"content": "Title: COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results Content: BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9-April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10-3.64), which increased to 2.61 (95% CI: 1.50-4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature &#8805; 37.5\u00b0C (3.49 (95% CI: 1.95-6.21)), and those with myalgias (1.83 (95% CI: 1.04-3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95-17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8-99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.", "qid": 26, "docid": "qziln7b6", "rank": 69, "score": 5.673399925231934}, {"content": "Title: COVID-19 symptoms predictive of healthcare workers\u2019 SARS-CoV-2 PCR results Content: BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9\u2014April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10\u20133.64), which increased to 2.61 (95% CI: 1.50\u20134.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature \u2265 37.5\u00b0C (3.49 (95% CI: 1.95\u20136.21)), and those with myalgias (1.83 (95% CI: 1.04\u20133.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95\u201317.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8\u201399.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.", "qid": 26, "docid": "z19ri377", "rank": 70, "score": 5.673398971557617}, {"content": "Title: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Content: The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).", "qid": 26, "docid": "7q9jady4", "rank": 71, "score": 5.658199787139893}, {"content": "Title: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Content: Abstract The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).", "qid": 26, "docid": "vhtc0jvq", "rank": 72, "score": 5.658198833465576}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID-19) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory-confirmed COVID-19. We conducted random-effects meta-analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty-six articles reporting 551 cases of COVID-19 in children (aged 1 day-17.5 years) were included. Eighty-seven percent (95% CI: 77%-95%) of patients had household exposure to COVID-19. The most common symptoms and signs were fever (53%, 95% CI: 45%-61%), cough (39%, 95% CI: 30%-47%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%-28%); however, 18% (95% CI: 11%-27%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%-43%) and ground glass opacities (28%, 95% CI: 18%-39%), but 36% (95% CI: 28%-45%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%-92%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID-19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID-19 case. Children with COVID-19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 26, "docid": "dqjwcm0i", "rank": 73, "score": 5.633500099182129}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta\u2010analysis of 551 laboratory\u2010confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID\u201019) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory\u2010confirmed COVID\u201019. We conducted random\u2010effects meta\u2010analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty\u2010six articles reporting 551 cases of COVID\u201019 in children (aged 1 day\u201017.5 years) were included. Eighty\u2010seven percent (95% CI: 77%\u201095%) of patients had household exposure to COVID\u201019. The most common symptoms and signs were fever (53%, 95% CI: 45%\u201061%), cough (39%, 95% CI: 30%\u201047%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%\u201028%); however, 18% (95% CI: 11%\u201027%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%\u201043%) and ground glass opacities (28%, 95% CI: 18%\u201039%), but 36% (95% CI: 28%\u201045%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%\u201092%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID\u201019 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID\u201019 case. Children with COVID\u201019 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 26, "docid": "hit7rs6q", "rank": 74, "score": 5.6334991455078125}, {"content": "Title: COVID-19 Anosmia Reporting Tool: Initial Findings. Content: There is accumulating anecdotal evidence that anosmia and dysgeusia are associated with the COVID-19 pandemic. To investigate their relationship to SARS-CoV2 infection, the American Academy of Otolaryngology-Head and Neck Surgery developed the COVID-19 Anosmia Reporting Tool for Clinicians for the basis of this pilot study. This tool allows health care providers to confidentially submit cases of anosmia and dysgeusia related to COVID-19. We analyzed the first 237 entries, which revealed that anosmia was noted in 73% of patients prior to COVID-19 diagnosis and was the initial symptom in 26.6%. Some improvement was noted in 27% of patients, with a mean time to improvement of 7.2 days in this group (85% of this group improved within 10 days). Our findings suggest that anomia can be a presenting symptom of COVID-19, consistent with other emerging international reports. Anosmia may be critical in timely identification of individuals infected with SARS-CoV2 who may be unwittingly transmitting the virus.", "qid": 26, "docid": "udy9wyu2", "rank": 75, "score": 5.63129997253418}, {"content": "Title: COVID-19 Anosmia Reporting Tool: Initial Findings Content: There is accumulating anecdotal evidence that anosmia and dysgeusia are associated with the COVID-19 pandemic. To investigate their relationship to SARS-CoV2 infection, the American Academy of Otolaryngology-Head and Neck Surgery developed the COVID-19 Anosmia Reporting Tool for Clinicians for the basis of this pilot study. This tool allows health care providers to confidentially submit cases of anosmia and dysgeusia related to COVID-19. We analyzed the first 237 entries, which revealed that anosmia was noted in 73% of patients prior to COVID-19 diagnosis and was the initial symptom in 26.6%. Some improvement was noted in 27% of patients, with a mean time to improvement of 7.2 days in this group (85% of this group improved within 10 days). Our findings suggest that anomia can be a presenting symptom of COVID-19, consistent with other emerging international reports. Anosmia may be critical in timely identification of individuals infected with SARS-CoV2 who may be unwittingly transmitting the virus.", "qid": 26, "docid": "xbkdylri", "rank": 76, "score": 5.631299018859863}, {"content": "Title: A retrospective study of the initial 25 COVID-19 patients in Luoyang, China Content: PURPOSE: To summarize the chest CT imaging and clinical features of the initial COVID-19 patients and provide a clinical diagnostic method that is more effective and can be performed earlier. METHODS: This retrospective study investigated the clinical, laboratory and imaging information of 25 patients in the Luoyang area. There were 15 (60%) male and 10 (40%) female patients ranging from 24 to 88 years old (52 \u00b1 19.30). Data were analyzed by Microsoft Excel and are expressed as the mean \u00b1 standard deviation or percentage. RESULTS: Thirteen (52%) patients had been in Wuhan or were in contact with people who had been in Wuhan, and ten (40%) patients were infected by their families or colleagues. The median time from initial symptoms to diagnosis was 7 days. Ninety-two percent of patients had respiratory symptoms, and 8% of them had digestive symptoms. Fever (92%), cough (60%) and fatigue (56%) were the most common symptoms. Most patients had a normal or reduced WBC (96%), reduced lymphocyte count (60%), increased CRP (48%) and increased ESR (44%). Ground glass opacity (GGO) was the typical radiological finding on chest CT. CONCLUSION: Characteristic chest CT imaging features could appear earlier than the viral nucleic acid assay results.", "qid": 26, "docid": "tqrjb1fe", "rank": 77, "score": 5.628900051116943}, {"content": "Title: A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments Content: The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.", "qid": 26, "docid": "zdyggb4o", "rank": 78, "score": 5.628699779510498}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge Content: BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS: This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19 METHODS: The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy RESULTS: The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue;while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19 CONCLUSIONS: The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress", "qid": 26, "docid": "lqfzte7w", "rank": 79, "score": 5.625199794769287}, {"content": "Title: COVID-19 and pregnancy: a review of current knowledge. Content: BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.", "qid": 26, "docid": "r4c7nldn", "rank": 80, "score": 5.625198841094971}, {"content": "Title: Measuring Icebergs: Using Different Methods to Estimate the Number of COVID-19 Cases in Portugal and Spain Content: The world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. The different national governments have problems evaluating the reach of the epidemic, having limited resources and tests at their disposal. Hence, any means to evaluate the number of persons with symptoms compatible with COVID-19 with reasonable level of accuracy is useful. In this paper we present the initial results of the @CoronaSurveys project. The objective of this project is the collection and publication of data concerning the number of people that show symptoms compatible with COVID-19 in different countries using open anonymous surveys. While this data may be biased, we conjecture that it is still useful to estimate the number of infected persons with the COVID-19 virus at a given point in time in these countries, and the evolution of this number over time. We show here the initial results of the @CoronaSurveys project in Spain and Portugal.", "qid": 26, "docid": "asj3r94u", "rank": 81, "score": 5.624000072479248}, {"content": "Title: Subjective Changes in Smell and Taste During the COVID-19 Pandemic: A National Survey-Preliminary Results. Content: Since the COVID-19 pandemic began, many individuals have noted acute loss of smell and/or taste, although not all patients with these symptoms are tested for COVID-19. To better characterize all patients with these rare symptoms, a national survey was created. Over 13 days in April 2020, a total of 220 people completed the survey in its entirety, representing a wide geographic distribution across the United States. Of the 220 respondents, 93 (42%) were diagnosed with COVID-19, and 127 (58%) were not. A total of 37.7% of respondents reported changes in smell/taste as the initial or sole presentation of their condition. Most but not all patients had other symptoms suggestive of COVID-19 at the time of chemosensory loss. Despite its inclusion as a major symptom of COVID-19 by the CDC (Centers for Disease Control and Prevention), respondents with additional CDC-defined symptoms associated with COVID-19 were statistically more likely to be tested/diagnosed than those without.", "qid": 26, "docid": "fqsmfuxl", "rank": 82, "score": 5.598199844360352}, {"content": "Title: Subjective Changes in Smell and Taste During the COVID-19 Pandemic: A National Survey-Preliminary Results Content: Since the COVID-19 pandemic began, many individuals have noted acute loss of smell and/or taste, although not all patients with these symptoms are tested for COVID-19. To better characterize all patients with these rare symptoms, a national survey was created. Over 13 days in April 2020, a total of 220 people completed the survey in its entirety, representing a wide geographic distribution across the United States. Of the 220 respondents, 93 (42%) were diagnosed with COVID-19, and 127 (58%) were not. A total of 37.7% of respondents reported changes in smell/taste as the initial or sole presentation of their condition. Most but not all patients had other symptoms suggestive of COVID-19 at the time of chemosensory loss. Despite its inclusion as a major symptom of COVID-19 by the CDC (Centers for Disease Control and Prevention), respondents with additional CDC-defined symptoms associated with COVID-19 were statistically more likely to be tested/diagnosed than those without.", "qid": 26, "docid": "okkrg30e", "rank": 83, "score": 5.598198890686035}, {"content": "Title: Uncommon presentation of COVID-19: Gastrointestinal bleeding Content: The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "qid": 26, "docid": "99c1wgid", "rank": 84, "score": 5.5980000495910645}, {"content": "Title: Uncommon Presentation Of Covid-19: Gastrointestinal Bleeding Content: SUMMARY The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "qid": 26, "docid": "xgr6r6of", "rank": 85, "score": 5.597999095916748}, {"content": "Title: Development and Initial Validation of the COVID Stress Scales Content: Abstract Research and clinical observations suggest that during times of pandemic many people exhibit stress- or anxiety-related psychopathology that include fear of becoming infected, fear of coming into contact with possibly contaminated objects or surfaces, fear of foreigners who might be carrying infection (i.e., disease-related xenophobia), fear of the socio-economic consequences of the pandemic, compulsive checking and reassurance-seeking regarding possible pandemic-related threats, and traumatic stress symptoms about the pandemic (e.g., nightmares, intrusive thoughts). We developed the 36-item COVID Stress Scales (CSS) to measure these features, as they pertain to COVID-19. The CSS were developed to better understand and assess COVID-19-related psychopathology. The scales were intentionally designed so they could be readily adapted for future pandemics. The CSS were developed and initially validated in population-representative samples from Canada (N = 3,479) and the United States (N = 3,375). A stable 5-factor solution was identified, corresponding to scales assessing COVID-related stress and anxiety symptoms: (1) Danger and contamination fears, (2) fears about economic consequences, (3) xenophobia, (4) compulsive checking, and (5) traumatic stress symptoms about COVID-19. The scales performed well on various indices of reliability and validity. The scales were intercorrelated, providing evidence of a COVID Stress Syndrome. The scales offer promise as tools for better understanding the psychopathology associated with COVID-19 and for identifying people in need of mental health services.", "qid": 26, "docid": "jn6zofl7", "rank": 86, "score": 5.580699920654297}, {"content": "Title: Development and initial validation of the COVID Stress Scales Content: Research and clinical observations suggest that during times of pandemic many people exhibit stress- or anxiety-related responses that include fear of becoming infected, fear of coming into contact with possibly contaminated objects or surfaces, fear of foreigners who might be carrying infection (i.e., disease-related xenophobia), fear of the socio-economic consequences of the pandemic, compulsive checking and reassurance-seeking regarding possible pandemic-related threats, and traumatic stress symptoms about the pandemic (e.g., nightmares, intrusive thoughts). We developed the 36-item COVID Stress Scales (CSS) to measure these features, as they pertain to COVID-19. The CSS were developed to better understand and assess COVID-19-related distress. The scales were intentionally designed so they could be readily adapted for future pandemics. The CSS were developed and initially validated in population-representative samples from Canada (N = 3479) and the United States (N = 3375). A stable 5-factor solution was identified, corresponding to scales assessing COVID-related stress and anxiety symptoms: (1) Danger and contamination fears, (2) fears about economic consequences, (3) xenophobia, (4) compulsive checking and reassurance seeking, and (5) traumatic stress symptoms about COVID-19. The scales performed well on various indices of reliability and validity. The scales were intercorrelated, providing evidence of a COVID Stress Syndrome. The scales offer promise as tools for better understanding the distress associated with COVID-19 and for identifying people in need of mental health services.", "qid": 26, "docid": "qp7kdyhy", "rank": 87, "score": 5.5806989669799805}, {"content": "Title: Optimising benefits of testing key workers for infection with SARS-CoV-2: A mathematical modelling analysis. Content: BACKGROUND Internationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates / quarantines many staff without SARS-CoV-2, whilst not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others. METHODS We used a decision-analytic model for 1,000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household-quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially-positive tests, initially-negative tests; or no re-testing. We varied all parameters, including the infection rate (0.1%-20%), proportion asymptomatic (10%-80%), sensitivity (60%-95%), and specificity (90%-100%). RESULTS Testing all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers per 1,000 tests (with reductions throughout at RT-PCR sensitivity of \u226565%), and absences by 0.5 to +3.6 days per test but at heightened testing needs of 989.6-1995.9 tests per 1,000 workers. Testing workers in household-quarantine (S2) reduces absences the most by 3.0-6.9 days per test (at 47.0-210.4 tests per 1,000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers per 1,000 tests (which can be minimised when re-testing initially-negative tests). DISCUSSION Based on optimising absence durations or transmission risk our modelling suggests testing staff in household-quarantine or all staff, depending on infection levels and testing capacities.", "qid": 26, "docid": "igpxdj5m", "rank": 88, "score": 5.565999984741211}, {"content": "Title: Optimising benefits of testing key workers for infection with SARS-CoV-2: A mathematical modelling analysis Content: BACKGROUND: Internationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates / quarantines many staff without SARS-CoV-2, whilst not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others. METHODS: We used a decision-analytic model for 1,000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household-quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially-positive tests, initially-negative tests; or no re-testing. We varied all parameters, including the infection rate (0.1%-20%), proportion asymptomatic (10%-80%), sensitivity (60%-95%), and specificity (90%-100%). RESULTS: Testing all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers per 1,000 tests (with reductions throughout at RT-PCR sensitivity of &#8805;65%), and absences by 0.5 to +3.6 days per test but at heightened testing needs of 989.6-1995.9 tests per 1,000 workers. Testing workers in household-quarantine (S2) reduces absences the most by 3.0-6.9 days per test (at 47.0-210.4 tests per 1,000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers per 1,000 tests (which can be minimised when re-testing initially-negative tests). DISCUSSION: Based on optimising absence durations or transmission risk our modelling suggests testing staff in household-quarantine or all staff, depending on infection levels and testing capacities.", "qid": 26, "docid": "uig5y33c", "rank": 89, "score": 5.5659990310668945}, {"content": "Title: Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19) Content: We present a case of coronavirus disease 2019 (COVID-19) with an initial medical presentation of keratoconjunctivitis, the first such reported case in North America. The patient's primary symptom was a red eye with watery discharge, though she did have mild respiratory symptoms, without fever. She was diagnosed with keratoconjunctivitis; evolving corneal findings were characterized through repeat visits to ophthalmology. A conjunctival swab of the affected eye was positive for the SAR-CoV-2 virus. This case emphasizes the importance of ensuring that first-line health care providers, including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of suspicion with this presentation would allow for appropriate precautions to be taken to prevent further spread of COVID-19.", "qid": 26, "docid": "edevlflf", "rank": 90, "score": 5.560400009155273}, {"content": "Title: Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19) Content: Abstract We present a case of coronavirus disease 2019 (COVID-19) with an initial medical presentation of keratoconjunctivitis, the first such reported case in North America. The patient's primary symptom was a red eye with watery discharge, though she did have mild respiratory symptoms, without fever. She was diagnosed with keratoconjunctivitis; evolving corneal findings were characterized through repeat visits to ophthalmology. A conjunctival swab of the affected eye was positive for the SAR-CoV-2 virus. This case emphasizes the importance of ensuring that first-line health care providers, including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of suspicion with this presentation would allow for appropriate precautions to be taken to prevent further spread of COVID-19.", "qid": 26, "docid": "ys7z7j8j", "rank": 91, "score": 5.560399055480957}, {"content": "Title: [Epidemiological characteristics of COVID-19 in Gansu province]. Content: Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend \u03c72=2.20, P<0.05) and fatigue (trend \u03c72=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.", "qid": 26, "docid": "aqyig0mb", "rank": 92, "score": 5.555500030517578}, {"content": "Title: [Epidemiological characteristics of COVID-19 in Gansu province] Content: Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend &#967;2=2.20, P<0.05) and fatigue (trend &#967;2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.", "qid": 26, "docid": "ecen7ke8", "rank": 93, "score": 5.555499076843262}, {"content": "Title: Five common skin manifestations of COVID\u201019 identified Content: COVID\u201019, also called coronavirus, is an infectious disease caused by SARS\u2010CoV\u20102. First identified in December 2019, in March 2020 it was announced by the World Health Organisation that COVID\u201019 had become a global pandemic. The disease can affect different organ systems, and early reports have suggested skin symptoms. The researchers, working with dermatologists across Spain, reviewed 375 patients with suspected, or confirmed, COVID\u201019, with the aim of developing a detailed classification of the different types of skin symptoms associated with COVID\u201019 with corresponding images. An initial 120 images were reviewed by four dermatologists, without knowing any other clinical information, and they identified patterns of symptoms associated with COVID\u201019. These patterns were then applied to the rest of the images and further refined. Five common skin symptoms were identified this way. These symptoms are chilblain\u2010like lesions, outbreaks of small blisters, wheals, rashes comprised of small flat and raised red bumps, and livedo and necrosis. Livedo is a skin condition where circulation is impaired within the blood vessels of the skin, necrosis refers to the premature death of skin tissue. These symptoms are associated with different severity of COVID\u201019 infection, from less severe disease in the chilblain\u2010like lesions, to most severe in patients with livedo. The researchers noted that some of the skin symptoms associated with COVID\u201019 are common and can have many causes, particularly wheals and rashes. As such, they may not be particularly helpful as an aide to diagnosis.", "qid": 26, "docid": "pb4d6jo0", "rank": 94, "score": 5.5543999671936035}, {"content": "Title: A Contemporary Review of Neurological Sequelae of COVID-19 Content: Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a \u201ccytokine storm\u201d can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.", "qid": 26, "docid": "411qyubx", "rank": 95, "score": 5.548999786376953}, {"content": "Title: [The Covid-19 pandemic and otolaryngology: What it comes down to?] Content: Here, we review the most recent findings on the effects COVID-19 pandemic for the work of otolaryngologists. The role of anosmia and hyposmia as a potential COVID-19 related symptom is presented. We discuss the clinical management of all ENT patients, but especially of COVID-19 patients from the ENT perspective. The impact of the infection on the ENT examination and ENT surgery is summarized.", "qid": 26, "docid": "ezyu6873", "rank": 96, "score": 5.548998832702637}, {"content": "Title: COVID-19 and Acute Pancreatitis: What Do Surgeons Need to Know? Content: Coronavirus disease 2019 (COVID-19) typically presents with pulmonary symptoms. Extra-pulmonary symptomatology of COVID-19 has drawn significant attention. However, information about the incidence, course and outcomes of acute pancreatitis in these patients is still limited.", "qid": 26, "docid": "umaxozwk", "rank": 97, "score": 5.5457000732421875}, {"content": "Title: The enduring grip of covid-19 Content: Contrary to medical expectation, many people with covid-19 are still experiencing symptoms weeks or even months later. Linda Geddes investigates what's going on", "qid": 26, "docid": "f95i3al5", "rank": 98, "score": 5.534599781036377}, {"content": "Title: Clinical Practice Guideline for the Evaluation of Fever and Infection in Older Adult Residents of Long\u2010Term Care Facilities: 2008 Update by the Infectious Diseases Society of America Content: Residents of long\u2010term care facilities (LTCFs) are at great risk for infection. Most residents are older and have multiple comorbidities that complicate recognition of infection; for example, typically defined fever is absent in more than one\u2010half of LTCF residents with serious infection. Furthermore, LTCFs often do not have the on\u2010site equipment or personnel to evaluate suspected infection in the fashion typically performed in acute care hospitals. In recognition of the differences between LTCFs and hospitals with regard to hosts and resources present, the Infectious Diseases Society of America first provided guidelines for evaluation of fever and infection in LTCF residents in 2000. The guideline presented here represents the second edition, updated by data generated over the intervening 8 years. It focuses on the typical elderly person institutionalized with multiple chronic comorbidities and functional disabilities (e.g., a nursing home resident). Specific topic reviews and recommendations are provided with regard to what resources are typically available to evaluate suspected infection, what symptoms and signs suggest infection in a resident of an LTCF, who should initially evaluate the resident with suspected infection, what clinical evaluation should be performed, how LTCF staff can effectively communicate about possible infection with clinicians, and what laboratory tests should be ordered. Finally, a general outline of how a suspected outbreak of a specific infectious disease should be investigated in an LTCF is provided.", "qid": 26, "docid": "wkhxbcue", "rank": 99, "score": 5.528299808502197}, {"content": "Title: The COVID-19 outbreak in Italy: initial implications for organ transplantation programs. Content: The spread of Coronavirus Disease 2019 (COVID-19) has already reached a pandemic dimension within few weeks. Italy has been one of the first countries dealing with the outbreak of COVID-19 and severe measures have been adopted to limit viral transmission. The spread of COVID-19 may have several implications in organ transplant activity that physicians should be aware of. The initial experience gained during the COVID-19 outbreak shows that around 10% of infected patients in Italy need intensive care management to overcome the acute respiratory distress syndrome. Due to the exponential rise of infected patients we are now facing an actual risk of saturation of intensive care unit (ICU) beds. A restriction in the number of ICU beds available for both donors and transplant recipients may unfavorably influence the overall donation activity, and eventually lead to a reduced number of transplants. Preliminary Italian data show that a 25% reduction of procured organs has already occurred during the first 4 weeks of COVID-19 outbreak. This underlines the need to closely monitor what will be further happening in ICUs due to the COVID-19 spread in the attempt to preserve transplant activity, especially in Western countries where deceased donors represent the major organ resource.", "qid": 26, "docid": "avbl3lfx", "rank": 100, "score": 5.524099826812744}]}
{"query": "what is known about those infected with Covid-19 but are asymptomatic?", "hits": [{"content": "Title: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review Content: BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "qid": 27, "docid": "998lscmk", "rank": 1, "score": 10.539999961853027}, {"content": "Title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Content: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: \u00e2\u0080\u00a2 There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: \u00e2\u0080\u00a2 Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. \u00e2\u0080\u00a2 However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.", "qid": 27, "docid": "u7arfoym", "rank": 2, "score": 9.768500328063965}, {"content": "Title: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Content: Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health", "qid": 27, "docid": "nadzy6lm", "rank": 3, "score": 9.708399772644043}, {"content": "Title: Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "qid": 27, "docid": "5j6uu16i", "rank": 4, "score": 9.526700019836426}, {"content": "Title: Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations. Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "qid": 27, "docid": "t0mqh9m0", "rank": 5, "score": 9.52669906616211}, {"content": "Title: Management of non traumatic surgical emergencies during the COVID-19 pandemia Content: In December 2019, in Wuhan, China, the first cases of what would be known as COVID-19, a disease caused by an RNA virus called SARS-CoV-2, were described Its spread was rapid and wide, leading the World Health Organization to declare a pandemic in March 2020 The disease has distinct clinical presentations, from asymptomatic to critical cases, with high lethality Parallel to this, patients with non-traumatic surgical emergencies, such as acute appendicitis and cholecystitis, continue to be treated at the emergency services In this regard, there were several doubts on how to approach these cases, among them: how to quickly identify the patient with COVID-19, what is the impact of the abdominal surgical disease and its treatment on the evolution of patients with COVID-19, in addition to the discussion about the role of the non-operative treatment for abdominal disease under these circumstances In this review, we discuss these problems based on the available evidence", "qid": 27, "docid": "vnq1fjwy", "rank": 6, "score": 9.48390007019043}, {"content": "Title: Audiological profile of asymptomatic Covid-19 PCR-positive cases Content: OBJECTIVE: The current study compared the amplitude of transient evoked otoacoustic emissions (TEOAEs) and latencies of vestibular evoked myogenic potentials (VEMPs) between asymptomatic COVID-19 PCR-positive cases and normal non-infected subjects. METHODS: Twenty cases who were confirmed positive for COVID-19 and had none of the known symptoms for this viral infection formed the test group for 2 full weeks. Their age ranged between 20 and 50 years to avoid any age-related hearing affection. Patients who had definite symptoms of COVID-19 infection as well as those who had a history of hearing loss or a history of any known cause of hearing loss were excluded from the examined sample. TEOAEs amplitude was measured for all participants. RESULTS: The high frequency pure-tone thresholds as well as the TEOAE amplitudes were significantly worse in the test group. CONCLUSIONS: COVID-19 infection could have deleterious effects on cochlear hair cell functions despite being asymptomatic. The mechanism of these effects requires further research.", "qid": 27, "docid": "8u7d4czd", "rank": 7, "score": 9.147600173950195}, {"content": "Title: Audiological profile of asymptomatic Covid-19 PCR-positive cases Content: OBJECTIVE: The current study compared the amplitude of transient evoked otoacoustic emissions (TEOAEs) and thresholds of pure-tone audiometry between asymptomatic COVID-19 PCR-positive cases and normal non-infected subjects. METHODS: Twenty cases who were confirmed positive for COVID-19 and had none of the known symptoms for this viral infection formed the test group. Their age ranged between 20 and 50 years to avoid any age-related hearing affection. Patients who had definite symptoms of COVID-19 infection as well as those who had a history of hearing loss or a history of any known cause of hearing loss were excluded from the examined sample. TEOAEs amplitude was measured for all participants. RESULTS: The high frequency pure-tone thresholds as well as the TEOAE amplitudes were significantly worse in the test group. CONCLUSIONS: COVID-19 infection could have deleterious effects on cochlear hair cell functions despite being asymptomatic. The mechanism of these effects requires further research.", "qid": 27, "docid": "zdmof6zb", "rank": 8, "score": 9.147599220275879}, {"content": "Title: Human and novel coronavirus infections in children: a review Content: Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS: 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Gu\u00e9rin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.", "qid": 27, "docid": "2zaxn6tq", "rank": 9, "score": 9.070899963378906}, {"content": "Title: Human and novel coronavirus infections in children: a review. Content: Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Gu\u00e9rin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.", "qid": 27, "docid": "5w194etz", "rank": 10, "score": 9.07089900970459}, {"content": "Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 27, "docid": "rs79r7kc", "rank": 11, "score": 9.037799835205078}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 27, "docid": "rsz7ch2a", "rank": 12, "score": 9.037798881530762}, {"content": "Title: The COVID-19 infection control arms race Content: US hospitals are engaged in an infection control arms race. Hospitals, specialties, and professional groups are spurring one another on to adopt progressively more aggressive measures in response to COVID-19 that often exceed federal and international standards. Examples include universal masking of providers and patients; decreasing thresholds to test asymptomatic patients; using face shields and N95 respirators regardless of symptoms and test results; novel additions to the list of aerosol-generating procedures; and more comprehensive personal protective equipment including hair, shoe, and leg covers. Here, we review the factors underlying this arms race, including fears about personal safety, ongoing uncertainty around how SARS-CoV-2 is transmitted, confusion about what constitutes an aerosol-generating procedure, increasing recognition of the importance of asymptomatic infection, and the limited accuracy of diagnostic tests. We consider the detrimental effects of a maximal infection control approach and the research studies that are needed to eventually de-escalate hospitals and to inform more evidence-based and measured strategies.", "qid": 27, "docid": "iy6rw8h5", "rank": 13, "score": 8.990599632263184}, {"content": "Title: COVID-19, Negligence and Occupational Health and Safety: Ethical and Legal Issues for Hospitals and Health Centres. Content: The international incidence of health workers being infected with COVID-19 is deeply troubling. Until a vaccine is developed, they are the community's bulwark against the pandemic. It is vital that they be protected to the maximum extent possible. This entails the need for implementation of effective and compassionate protocols to keep their workplace as safe as possible for them, their colleagues and their patients in a context of much as yet not being known about the virus and awareness that some persons infected by it are for a time at least asymptomatic and that others test negative for it when they are prodromal or even already displaying some symptomatology. This has repercussions both for the liability of hospitals and multi-practitioner centres for negligence and also under occupational health and safety legislation. With the commencement of the roll out of biosecurity and disaster/emergency measures by government and escalating levels of anxiety in the general population, it is important to reflect upon the measures that most effectively can be adopted practically and ethically to protect the health and safety of those whose task it is to care for us if we become infected by COVID-19.", "qid": 27, "docid": "i3i3xuc6", "rank": 14, "score": 8.963800430297852}, {"content": "Title: COVID-19, Negligence and Occupational Health and Safety: Ethical and Legal Issues for Hospitals and Health Centres Content: The international incidence of health workers being infected with COVID-19 is deeply troubling. Until a vaccine is developed, they are the community's bulwark against the pandemic. It is vital that they be protected to the maximum extent possible. This entails the need for implementation of effective and compassionate protocols to keep their workplace as safe as possible for them, their colleagues and their patients in a context of much as yet not being known about the virus and awareness that some persons infected by it are for a time at least asymptomatic and that others test negative for it when they are prodromal or even already displaying some symptomatology. This has repercussions both for the liability of hospitals and multi-practitioner centres for negligence and also under occupational health and safety legislation. With the commencement of the roll out of biosecurity and disaster/emergency measures by government and escalating levels of anxiety in the general population, it is important to reflect upon the measures that most effectively can be adopted practically and ethically to protect the health and safety of those whose task it is to care for us if we become infected by COVID-19.", "qid": 27, "docid": "var1ftgr", "rank": 15, "score": 8.963799476623535}, {"content": "Title: ACE 2 Coding Variants: A Potential X-linked Risk Factor for COVID-19 Disease Content: Viral genetic variants are widely known to influence disease progression among infected humans. Given the recent and rapid emergence of pandemic SARS-CoV-2 infection, the cause of COVID-19 disease, viral protein variants have attracted research interest. However, little has yet been written about genetic risk factors among human hosts. Human genetic variation has proven to affect disease progression and outcome for important diseases such as HIV infection and malaria infestation. The fact that the human ACE2 protein is encoded on the X chromosome means that males who carry rare ACE2 coding variants will express those variants in all ACE2-expressing cells, whereas females will typically express those variants in a mosaic distribution determined by early X-inactivation events. This sex-based difference in ACE2 expression has unique implications for epidemiological studies designed to assess host genetic factors influencing progression from asymptomatic SARS-coV-2 infection to COVID-19. Here we present theoretical modelling of rare ACE2 coding variants documented to occur naturally in several human superpopulations and subpopulations, and show that rare variants predicted to affect the binding of ACE2 to the SARS-CoV-2 spike protein exist in people. Though the rs4646116 (p.Lys26Arg) allele is found in 1 in 70 Ashkenazi Jewish males, and in 1 in 172 non-Finnish European males, this allele is found at higher frequencies in females. Furthermore, the class of missense ACE2 alleles predicted to affect SARS-CoV-2 binding are found in aggregate among 1.43% and 2.16% of Ashkenazi males and females, respectively, as well as in 0.58% and 1.24% of European males and females outside of Finland. These alleles are rarer in other population groups, and almost absent from East Asians genotyped to date. Though we are aware that full genome-wide and exome-wide sequencing studies may ultimately be required to assess human genetic susceptibility to SARS-CoV-2 fully, we argue on the basis of strong prior probabilities that genotyping of this class of alleles is justified in cases of atypical SARS-CoV-2 diseases, such as asymptomatic super-spreaders (if any are identified), and in neonatal/paediatric-onset COVID-19 disease. Even relatively rare susceptibility factors (1% or fewer carriers) may become quantitatively important in the context of hundreds of thousands of infections. A small number of asymptomatic carriers, or a small number of super-spreaders, or a small segment of the population that is disproportionately likely to require intensive care, can magnify the medical, social and economic impacts of a pandemic of this size. The speed of the pandemic and the large number of affected cases worldwide justify efforts to identify all possible risk factors for adverse outcomes, including efforts to identify genetic susceptibility factors in human hosts.", "qid": 27, "docid": "05w8tv8x", "rank": 16, "score": 8.905699729919434}, {"content": "Title: A Review of Asymptomatic and Subclinical Middle East Respiratory Syndrome Coronavirus Infections Content: The epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) since 2012 has been largely characterized by recurrent zoonotic spillover from dromedary camels followed by limited human-to-human transmission, predominantly in health-care settings. The full extent of infection of MERS-CoV is not clear, nor is the extent and/or role of asymptomatic infections in transmission. We conducted a review of molecular and serological investigations through PubMed and EMBASE from September 2012 to November 15, 2018, to measure subclinical or asymptomatic MERS-CoV infection within and outside of health-care settings. We performed retrospective analysis of laboratory-confirmed MERS-CoV infections reported to the World Health Organization to November 27, 2018, to summarize what is known about asymptomatic infections identified through national surveillance systems. We identified 23 studies reporting evidence of MERS-CoV infection outside of health-care settings, mainly of camel workers, with seroprevalence ranges of 0%\u201367% depending on the study location. We identified 20 studies in health-care settings of health-care worker (HCW) and family contacts, of which 11 documented molecular evidence of MERS-CoV infection among asymptomatic contacts. Since 2012, 298 laboratory-confirmed cases were reported as asymptomatic to the World Health Organization, 164 of whom were HCWs. The potential to transmit MERS-CoV to others has been demonstrated in viral-shedding studies of asymptomatic MERS infections. Our results highlight the possibility for onward transmission of MERS-CoV from asymptomatic individuals. Screening of HCW contacts of patients with confirmed MERS-CoV is currently recommended, but systematic screening of non-HCW contacts outside of health-care facilities should be encouraged.", "qid": 27, "docid": "udn2t8il", "rank": 17, "score": 8.903400421142578}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child's will must not be forced.Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation. What is Known: \u00e2\u0080\u00a2 Asymptomatic people can transmit and become important sources of COVID-19. \u00e2\u0080\u00a2 Asymptomatic cases are common also in pediatrics. What is New: \u00e2\u0080\u00a2 Universal use of face masks for success against COVID-19 seems necessary also in pediatric age when people have to go out in their everyday lives. \u00e2\u0080\u00a2 In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons with the main aim to obtain child cooperation.", "qid": 27, "docid": "471z07ac", "rank": 18, "score": 8.791000366210938}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index &#8805;40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 27, "docid": "3jwl97qb", "rank": 19, "score": 8.786199569702148}, {"content": "Title: The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy. Content: The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index \u226540), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to \"shelter in place,\" quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to \"flatten the curve\" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity.", "qid": 27, "docid": "7ofa04l1", "rank": 20, "score": 8.786198616027832}, {"content": "Title: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Content: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining", "qid": 27, "docid": "3wuh6k6g", "rank": 21, "score": 8.753399848937988}, {"content": "Title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID-19: Meta-analysis and sensitivity analysis Content: The coronavirus disease-2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscript conducts a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% CI (2.41-3.90), the average incubation time to be 5.08 days with the 95% CI (4.77-5.39) (in day), the asymptomatic infection rate to be 46% with the 95% CI (18.48%-73.60%), and the case fatality rate to be 2.72% with 95% CI (1.29%-4.16%) where asymptomatic infections are accounted for.", "qid": 27, "docid": "dt0b87me", "rank": 22, "score": 8.730199813842773}, {"content": "Title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID\u201019: Meta\u2010analysis and sensitivity analysis Content: The coronavirus disease\u20102019 (COVID\u201019) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102). However, comprehensive knowledge of COVID\u201019 remains incomplete and many important features are still unknown. This manuscript conducts a meta\u2010analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% CI (2.41\u20103.90), the average incubation time to be 5.08 days with the 95% CI (4.77\u20105.39) (in day), the asymptomatic infection rate to be 46% with the 95% CI (18.48%\u201073.60%), and the case fatality rate to be 2.72% with 95% CI (1.29%\u20104.16%) where asymptomatic infections are accounted for.", "qid": 27, "docid": "fraczoxu", "rank": 23, "score": 8.730198860168457}, {"content": "Title: Prevalence of positive COVID-19 among asymptomatic health care workers who care patients infected with the novel coronavirus: A retrospective study Content: BACKGROUND: Limited information is available about COVID-19 infections among health care workers. Sensitive detection of COVID-19 cases in health care workers is crucial for hospital infection prevention policy, particularly for those who work with vulnerable patients. The aim of this study is to describe the prevalence of positive COVID-19 among asymptomatic health care workers who took care of patients with COVID-19 during the pandemic. METHODS: This retrospective study included all health care workers at King Abdullah University Hospital who take care of patients infected with COVID-19 patients from March 18, 2020 to April 29, 2020. They were tested for COVID-19 infection by use of real-time reverse-transcriptase rRT-PCR on samples from nasopharyngeal swabs. RESULTS: A total number of 370 health care workers were screened. The majority were nurses followed by physicians and other personnel. This study showed that all asymptomatic health care workers were tested negative for COVID-19Q. CONCLUSION: Unexpectedly, the prevalence of positive COVID-19 among asymptomatic health care workers who take care of patients infected with the novel coronavirus was 0%. This result must be cautiously interpreted. Further studies are needed in order to find effective strategy of screening health care workers to insure a safe working environment.", "qid": 27, "docid": "hvo5smwx", "rank": 24, "score": 8.657600402832031}, {"content": "Title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate forCOVID-19: Meta-analysis and sensitivity analysis Content: The coronavirus disease 2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscripts conduct a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% interval (2.41, 3.90), the average incubation time to be 5.08 days with the 95% confidence interval (4.77, 5.39) (in day), the asymptomatic infection rate to be 46% with the 95% confidence interval (18.48%, 73.60%), and the case fatality rate to be 2.72% with 95% confidence interval (1.29%, 4.16%) where asymptomatic infections are accounted for.", "qid": 27, "docid": "1ew0p6x7", "rank": 25, "score": 8.596500396728516}, {"content": "Title: COVID-19 and the Heart. Content: Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 27, "docid": "d4h49d8b", "rank": 26, "score": 8.419099807739258}, {"content": "Title: COVID-19 and the Heart Content: Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 27, "docid": "dn41mqmb", "rank": 27, "score": 8.374199867248535}, {"content": "Title: Prudent public health intervention strategies to control the coronavirus disease 2019 transmission in India: A mathematical model-based approach Content: BACKGROUND & OBJECTIVES: Coronavirus disease 2019 (COVID-19) has raised urgent questions about containment and mitigation, particularly in countries where the virus has not yet established human-to-human transmission. The objectives of this study were to find out if it was possible to prevent, or delay, the local outbreaks of COVID-19 through restrictions on travel from abroad and if the virus has already established in-country transmission, to what extent would its impact be mitigated through quarantine of symptomatic patients? METHODS: These questions were addressed in the context of India, using simple mathematical models of infectious disease transmission. While there remained important uncertainties in the natural history of COVID-19, using hypothetical epidemic curves, some key findings were illustrated that appeared insensitive to model assumptions, as well as highlighting critical data gaps. RESULTS: It was assumed that symptomatic quarantine would identify and quarantine 50 per cent of symptomatic individuals within three days of developing symptoms. In an optimistic scenario of the basic reproduction number (R(0)) being 1.5, and asymptomatic infections lacking any infectiousness, such measures would reduce the cumulative incidence by 62 per cent. In the pessimistic scenario of R(0)=4, and asymptomatic infections being half as infectious as symptomatic, this projected impact falls to two per cent. INTERPRETATION & CONCLUSIONS: Port-of-entry-based entry screening of travellers with suggestive clinical features and from COVID-19-affected countries, would achieve modest delays in the introduction of the virus into the community. Acting alone, however, such measures would be insufficient to delay the outbreak by weeks or longer. Once the virus establishes transmission within the community, quarantine of symptomatics may have a meaningful impact on disease burden. Model projections are subject to substantial uncertainty and can be further refined as more is understood about the natural history of infection of this novel virus. As a public health measure, health system and community preparedness would be critical to control any impending spread of COVID-19 in the country.", "qid": 27, "docid": "v88f9e7m", "rank": 28, "score": 8.339699745178223}, {"content": "Title: Covid-19 in pregnant women and babies: What pediatricians need to know Content: Beginning in late 2019, a novel coronavirus labeled SARS-CoV-2 spread around the world, affecting millions. The impact of the disease on patients and on health care delivery has been unprecedented. Here, we review what is currently known about the effects of the virus and its clinical condition, Covid-19 in areas of relevance to those providing care to neonates. While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this. Viral carriage prevalence based on universal screening show that rates vary from 13% in \u201chot spots\u201d such as New York City, to 3% in areas with lower cases. Vertical transmission risks are unknown but 3.1% of 311 babies born to mothers with Covid-19 were positive within a week of birth. The clinical description of 26 neonates < 30 days of age showed no deaths and only one requiring intensive care. Risks for breast-feeding and for milk banks are discussed.", "qid": 27, "docid": "fllqdn4s", "rank": 29, "score": 8.329999923706055}, {"content": "Title: The COVID-19 (SARS-CoV-2) Uncertainty Tripod in Brazil: Assessments on model-based predictions with large under-reporting Content: The COVID-19 pandemic (SARS-CoV-2 virus) is the defying global health crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We propose an adapted Susceptible-Infected-Recovered (SIR) model which explicitly incorporates the under-reporting and the response of the population to public policies (such as confinement measures, widespread use of masks, etc) to cast short-term and long-term predictions. Large amounts of uncertainty could provide misleading models and predictions. In this paper, we discuss the role of uncertainty in these prediction, which is illustrated regarding three key aspects. First, assuming that the number of infected individuals is under-reported, we demonstrate an anticipation regarding the peak of infection. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic. Second, considering that the actual amount of deaths is larger than what is being register, then demonstrate the increase of the mortality rates. Third, when consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the effect of the\"COVID-19 under-reporting tripod\", i.e. the under-reporting in terms of infected individuals, of deaths and the true mortality rate. If two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates.", "qid": 27, "docid": "8cw3bjxh", "rank": 30, "score": 8.319899559020996}, {"content": "Title: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Content: BACKGROUND: Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. METHODS: We retrospectively retrieved data for paediatric patients (aged 0-16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. FINDINGS: From Jan 17 to March 1, 2020, 36 children (mean age 8\u00b73 [SD 3\u00b75] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38\u00b75\u00b0C or higher, and nine (25%) had a body temperature of 37\u00b75-38\u00b75\u00b0C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir-ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. INTERPRETATION: Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. FUNDING: Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.", "qid": 27, "docid": "12sakknb", "rank": 31, "score": 8.317700386047363}, {"content": "Title: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Content: Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0\u201316 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8\u00b73 [SD 3\u00b75] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38\u00b75\u00b0C or higher, and nine (25%) had a body temperature of 37\u00b75\u201338\u00b75\u00b0C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir\u2013ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.", "qid": 27, "docid": "dmrtsxik", "rank": 32, "score": 8.317699432373047}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10(th) and April 4(th), 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "bfe8e0wu", "rank": 33, "score": 8.298700332641602}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: Background: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. Methods: We conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results: Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. Conclusions: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "js5my502", "rank": 34, "score": 8.298699378967285}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "pf2pj6mo", "rank": 35, "score": 8.298698425292969}, {"content": "Title: Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. Content: BACKGROUND Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms, but little is known about their relationship with severe respiratory illness. OBJECTIVE To compare the prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever (ARI/fever) with that among asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV infection compared with other respiratory viruses. METHODS From December 2003 to April 2004 and October 2004 to April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in 3 US counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by real-time reverse-transcription polymerase chain reaction. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review. RESULTS Overall, HCoV was detected in 113 (7.6%) of 1481 hospitalized children (83 [5.7%] after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, whereas those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone. CONCLUSIONS In this study of children hospitalized for ARI/fever, HCoV infection was not associated with hospitalization or with increased severity of illness.", "qid": 27, "docid": "vbye4nrj", "rank": 36, "score": 8.295999526977539}, {"content": "Title: What orthopedic surgeons need to know about Covid-19 pandemic Content: The ongoing outbreak of COVID-19, also known as SARS-CoV-2 and coronavirus disease 2019, is considered a major public concern that propagates steadily by the increased number of the infected cases and the mortality rate. In this article, we provide a brief review for Orthopedic surgeons as regard COVID-19 virus microbiology, epidemiology, clinical picture, and diagnosis. Moreover, what measures should be taken amid this pandemic to assess its control, maintain the urgent duties, and protect health care workers (HCW) are also discussed.", "qid": 27, "docid": "9pmix2zq", "rank": 37, "score": 8.262800216674805}, {"content": "Title: What orthopedic surgeons need to know about Covid-19 pandemic() Content: The ongoing outbreak of COVID-19, also known as SARS-CoV-2 and coronavirus disease 2019, is considered a major public concern that propagates steadily by the increased number of the infected cases and the mortality rate. In this article, we provide a brief review for Orthopedic surgeons as regard COVID-19 virus microbiology, epidemiology, clinical picture, and diagnosis. Moreover, what measures should be taken amid this pandemic to assess its control, maintain the urgent duties, and protect health care workers (HCW) are also discussed.", "qid": 27, "docid": "bbnbnwte", "rank": 38, "score": 8.262799263000488}, {"content": "Title: Lived experiences of the Corona Survivors (patients admitted in COVID wards): A Narrative real-life documented summaries of internalized guilt, shame, stigma, anger Content: COVID-19 pandemic has emerged as a disaster for the human beings. All the Governments across the globe have been preparing to deal with this medical emergency, which is known to be associated with mortality in about 5% of the sufferers. Gradually, it is seen that, many patients with COVID-19 infection have mild symptoms or are asymptomatic. Due to the risk of infecting others, persons with COVID-19 infection are kept in isolation wards. Because of the isolation, the fear of death, and associated stigma, many patients with COVID-19 infection go through mental distress. In this report, we discuss the experience of 3 persons diagnosed with COVId-19 infection and admitted to the COVID ward.", "qid": 27, "docid": "6xy8bwfl", "rank": 39, "score": 8.254300117492676}, {"content": "Title: Lived experiences of the corona survivors (patients admitted in COVID wards): A narrative real-life documented summaries of internalized guilt, shame, stigma, anger Content: COVID-19 pandemic has emerged as a disaster for the human beings. All the Governments across the globe have been preparing to deal with this medical emergency, which is known to be associated with mortality in about 5% of the sufferers. Gradually, it is seen that, many patients with COVID-19 infection have mild symptoms or are asymptomatic. Due to the risk of infecting others, persons with COVID-19 infection are kept in isolation wards. Because of the isolation, the fear of death, and associated stigma, many patients with COVID-19 infection go through mental distress. In this report, we discuss the experience of 3 persons diagnosed with COVId-19 infection and admitted to the COVID ward.", "qid": 27, "docid": "ue7rd2yt", "rank": 40, "score": 8.25429916381836}, {"content": "Title: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Content: Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.", "qid": 27, "docid": "c5be70t6", "rank": 41, "score": 8.224100112915039}, {"content": "Title: Dealing with sleep problems during home confinement due to the COVID-19 outbreak: Practical recommendations from a task force of the European CBT-I Academy Content: In the current global home confinement situation due to the COVID-19 outbreak, most individuals are exposed to an unprecedented stressful situation of unknown duration. This may not only increase daytime stress, anxiety and depression levels, but also disrupt sleep. Importantly, because of the fundamental role that sleep plays in emotion regulation, sleep disturbance can have direct consequences upon next day emotional functioning. In this paper, we summarize what is known about the stress-sleep link and confinement as well as effective insomnia treatment. We discuss those effects of the current home confinement situation that can disrupt sleep but also those that could benefit sleep quality. We suggest adaptions of cognitive behavioural therapy elements that are feasible to implement for those facing changed work schedules and requirements, those with health anxiety and those handling childcare and home-schooling, whilst also recognizing the general limitations imposed on physical exercise and social interaction. Managing sleep problems as best as possible during home confinement can limit stress and possibly prevent disruptions of social relationships.", "qid": 27, "docid": "lf6t8xmm", "rank": 42, "score": 8.221199989318848}, {"content": "Title: Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy. Content: In the current global home confinement situation due to the COVID-19 outbreak, most individuals are exposed to an unprecedented stressful situation of unknown duration. This may not only increase daytime stress, anxiety and depression levels but also disrupt sleep. Importantly, because of the fundamental role that sleep plays in emotion regulation, sleep disturbance can have direct consequences upon next day emotional functioning. In this paper we summarize what is known about the stress-sleep link and confinement as well as effective insomnia treatment. We discuss those effects of the current home confinement situation that can disrupt sleep but also those that could benefit sleep quality. We suggest adaptions of cognitive behavioral therapy elements that are feasible to implement for those facing changed work schedules and requirements, those with health anxiety and those handling childcare and homeschooling, whilst also recognizing the general limitations imposed on physical exercise and social interaction. Managing sleep problems as best as possible during home confinement can limit stress and possibly prevent disruptions of social relationships.", "qid": 27, "docid": "x1ffjbvi", "rank": 43, "score": 8.221199035644531}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 27, "docid": "fqs40ivc", "rank": 44, "score": 8.1943998336792}, {"content": "Title: Chest Computed Tomography Findings in Asymptomatic Patients with COVID-19 Content: Background: Little is known about the damage to the respiratory system in asymptomatic patients with coronavirus disease (COVID-19). Objective: Herein, we evaluated the findings of chest computed tomography (CT) and radiography in patients with COVID-19 who were asymptomatic. Methods: We retrospectively investigated patients with a confirmed diagnosis of COVID-19 but who did not show any symptoms. Among the 139 patients with COVID-19 who were hospitalized, 10 (7.2%) were asymptomatic. Their chest CT and radiographic findings were analyzed. Results: In the results, all patients (100%) had ground glass opacity (GGO) on chest CT. Further, the GGO lesions were predominantly distributed peripherally and posteriorly in all patients. In 9 (90%) patients, the GGO lesions were combined with reticular opacity. Air-bronchogram due to bronchiolectasis surrounded by GGO was observed in 8 patients (80%). Additionally, the lung lesions were dominant on the right side in all patients. Conclusions: In conclusion, considering our results that the lung is affected in asymptomatic patients, it will be necessary to extend the indications of COVID-19 testing for effective management of COVID-19 during the pandemic.", "qid": 27, "docid": "4hfmst53", "rank": 45, "score": 8.115500450134277}, {"content": "Title: Asymptomatic SARS-CoV-2 infection and COVID-19 mortality during an outbreak investigation in a skilled nursing facility Content: BACKGROUND: Outbreaks of COVID-19 have been reported in nursing homes and assisted living facilities; however, the extent of asymptomatic and pre-symptomatic SARS-CoV-2 infection in this high-risk population remains unclear. METHODS: We conducted an investigation of the first known outbreak of SARS-CoV-2 at a skilled nursing facility (SNF) in Illinois on March 15, 2020 and followed residents for 30 days. We tested 126/127 residents for SARS-CoV-2 via RT-PCR and performed symptom assessments. We calculated the point prevalence of SARS-CoV-2 and assessed symptom onset over 30-day follow-up to determine: 1) the proportion of cases who were symptomatic, pre-symptomatic, and asymptomatic and 2) incidence of symptoms among those who tested negative. We used the Kaplan-Meier method to determine the 30-day probability of death for cases. RESULTS: Of 126 residents tested, 33 had confirmed SARS-CoV-2 on March 15. Nineteen (58%) had symptoms at the time of testing, 1 (3%) developed symptoms over follow-up, and 13 (39%) remained asymptomatic. Thirty-five residents who tested negative on March 15 developed symptoms over follow-up; of these, 3 were re-tested and 2 were positive. The 30-day probability of death among cases was 29%. CONCLUSIONS: SNFs are particularly vulnerable to SARS-CoV-2, and residents are at risk of severe outcomes. Attention must be paid to preventing outbreaks in these and other congregate care settings. Widespread testing and infection control are key to help prevent COVID-19 morbidity and mortality in these high-risk populations.", "qid": 27, "docid": "ohnyc3i0", "rank": 46, "score": 8.083499908447266}, {"content": "Title: Asymptomatic COVID-19 Have Longer Treatment Cycle Than Moderate Type of Confirmed Patients Content: IMPORTANCE A kind of pneumonia caused by unknown causes that occurred in Wuhan, Hubei, China in December 2019, was reported as a result of novel coronavirus infection on January 7, 2020, and then WHO named it \"COVID-19\". The comparison of epidemiological and clinical characteristics for those patients between asymptomatic COVID-19 infections and moderate type of confirmed cases is limited. OBJECTIVE To compare the difference of epidemiology and clinical characteristics between asymptomatic COVID-19 infections and moderate type of confirmed cases. DESIGN, SETTING, AND PARTICIPANTS Retrospective, single-center cohort study of COVID-19 involving 52 infections of both 26 asymptomatic and 26 moderate type of confirmed cases in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. This study was registered in Chinese Clinical Trial Registry Center. EXPOSURES Documented the asymptomatic COVID-19 infections and moderate type of confirmed cases. MAIN OUTCOMES AND MEASURES Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of asymptomatic COVID-19 infections and moderate type of confirmed cases were compared. RESULTS The median treatment cycle of asymptomatic COVID-19 infections was 16 days (interquartile range, 11-20 days) and longer than 13 days (interquartile range, 10-15 days) of moderate type of confirmed cases (p=0.049). The median incubation period of asymptomatic COVID-19 infections was 10 days (interquartile range, 0-21 days), while the control group was 7 days (interquartile range, 1-15 days) (p=0.27). On the initial chest computerized tomography (CT) check, 18 (69.2%, 18/26) asymptomatic COVID-19 infections were no imaging changes, which was of no significance compared with 12 (46.2%, 12/26) patients with moderate type of confirmed patients (p=0.092). CONCLUSIONS AND RELEVANCE In this single-center study, we found that asymptomatic COVID-19 infections have longer treatment cycle than those moderate type of confirmed cases.", "qid": 27, "docid": "6vxc7wv0", "rank": 47, "score": 8.062000274658203}, {"content": "Title: SARS-CoV-2, COVID-19, skin and immunology - what do we know so far? Content: The pandemic condition Coronavirus-disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2 positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial and maculopapular eruptions as well as livedo, necrosis and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical and histologic features of virus- as well as drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.", "qid": 27, "docid": "t8pltw5x", "rank": 48, "score": 8.016599655151367}, {"content": "Title: COVID-19 \u2013 What does a paediatrician need to know? Content: COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.", "qid": 27, "docid": "828ubhzi", "rank": 49, "score": 8.01039981842041}, {"content": "Title: Adding the missing sugars to coronavirus protein structures Content: Protein structures solved by cryo-electron microscopy (cryo-EM) or X-ray crystallography often miss the sugar molecules known as glycans that cover large swaths of the proteins\u2019 surfaces The recently reported structures of the spike protein on SARS-CoV-2, the novel coronavirus that causes COVID-19, are no different Researchers are now working to fill in some of those sugary blanks to better understand the virus\u2019s biology and to help drugmakers develop vaccines and treatments \u201cPeople usually go for what they can analyze\u201d and focus mostly on the protein components of a structure, says Andrea Thorn, a structural biologist at the Julius Maximilian University of W\u00fcrzburg She is a member of the Coronavirus Structural Task Force, a group of scientists who specialize in modeling and processing crystallographic and cryo-EM data Because structural biology measurements don\u2019t reveal much about glycans on proteins, \u201cwe often fail to recognize what an important part of the structure they", "qid": 27, "docid": "fayr38c7", "rank": 50, "score": 7.9857001304626465}, {"content": "Title: 2019 Novel Coronavirus: What Is Currently Known, Cardiovascular Implications and Management Content: From first cases reported on December 31, 2019, in Wuhan, Hubei-China, SARS-CoV2 has spread worldwide and finally the World Health Organization declared the pandemic status. We summarize what makes SARS-CoV2 different from previous highly pathogenic coronaviruses and why it is so contagious, with focus on its clinical presentation and diagnosis, which is mandatory to start the appropriate management and reduce the transmission. As far as infection pathophysiology is still not completely clarified, this review focuses also on the cardiovascular (CV) implication of COVID-19 and the capability of this virus to cause direct myocardial injury, myocarditis and other CV manifestations. Furthermore, we highlight the relationship between the virus, enzyme ACE2 and ACE inhibitors. Clinical management involves the intensive care approach with intubation and mechanical ventilation in the most serious cases and drug therapy with several apparently promising old and new molecules. Aim of this review is then to summarize what is actually known about the SARS-CoV2 and its cardiovascular implications.", "qid": 27, "docid": "ubuetsi3", "rank": 51, "score": 7.9822998046875}, {"content": "Title: 2019 novel coronavirus: what is currently known, cardiovascular implications and management. Content: From first cases reported on December 31, 2019, in Wuhan, Hubei-China, SARS-CoV2 has spread worldwide and finally the World Health Organization declared the pandemic status. We summarize what makes SARS-CoV2 different from previous highly pathogenic coronaviruses and why it is so contagious, with focus on its clinical presentation and diagnosis, which is mandatory to start the appropriate management and reduce the transmission. As far as infection pathophysiology is still not completely clarified, this review focuses also on the cardiovascular (CV) implication of COVID-19 and the capability of this virus to cause direct myocardial injury, myocarditis and other CV manifestations. Furthermore, we highlight the relationship between the virus, enzyme ACE2 and ACE inhibitors. Clinical management involves the intensive care approach with intubation and mechanical ventilation in the most serious cases and drug therapy with several apparently promising old and new molecules. Aim of this review is then to summarize what is actually known about the SARS-CoV2 and its cardiovascular implications.", "qid": 27, "docid": "zolktlsj", "rank": 52, "score": 7.982298851013184}, {"content": "Title: Is there an airborne component to the transmission of COVID-19? : a quantitative analysis study Content: Objectives While COVID-19 is known to be spread by respiratory droplets (which travel <2m horizontally), much less is known about its transmission via aerosols, which can become airborne and be widely distributed throughout room spaces. In order to quantify the risk posed by COVID-19 infectors exhaling respiratory aerosols in enclosed spaces, we undertook a computer modelling study to simulate transmission in an office building. Methods Respiratory droplet data from four published datasets were analysed to quantify the number and volume of droplets <100m diameter produced by a typical cough and speaking event (i.e. counting from 1 to 100). This was used in a stochastic model to simulate (10,000 simulations) the number of respiratory particles, originating from a COVID-19 infector, that would be inhaled in one hour by a susceptible individual practicing socially distancing in a 5 x 5 x 2.75m office space. Several scenarios were simulated that mimicked the presence of both symptomatic and asymptomatic COVID-19 infectors. Results On average, each cough and speaking event produced similar numbers of droplets <100 m diameter (median range = 955 - 1010). Computer simulations (at ventilation rate = 2AC/h) revealed that sharing the office space with a symptomatic COVID-19 infector (4 coughs per hour) for one hour resulted in the inhalation of 187.3 (median value) respiratory droplets, whereas sharing with an asymptomatic COVID-19 positive person (10 speaking events per hour) resulted in the inhalation of 482.9 droplets. Increasing the ventilation rate resulted in only modest reductions in particle numbers inhaled. Conclusions Given that live SARS-CoV-2 virions are known to be shed in high concentrations from the nasal cavity of both symptomatic and asymptomatic COVID-19 patients, the results suggest that individuals who share enclosed spaces with an infector may be at risk of contracting COVID-19 by the aerosol route, even when practicing social distancing.", "qid": 27, "docid": "a0oxgop2", "rank": 53, "score": 7.978400230407715}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 27, "docid": "abj9b0x0", "rank": 54, "score": 7.973800182342529}, {"content": "Title: Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention. Content: Across two studies with more than 1,700 U.S. adults recruited online, we present evidence that people share false claims about COVID-19 partly because they simply fail to think sufficiently about whether or not the content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they were asked directly about accuracy. Furthermore, greater cognitive reflection and science knowledge were associated with stronger discernment. In Study 2, we found that a simple accuracy reminder at the beginning of the study (i.e., judging the accuracy of a non-COVID-19-related headline) nearly tripled the level of truth discernment in participants' subsequent sharing intentions. Our results, which mirror those found previously for political fake news, suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media.", "qid": 27, "docid": "zbkgabl2", "rank": 55, "score": 7.973799228668213}, {"content": "Title: From SARS to COVID-19: What we have learned about children infected with COVID-19 Content: Abstract Coronaviruses, both SARS-CoV and SARS-CoV-2 were firstly appeared in China. They have certain similarities in biological, epidemiological and pathological. To data, the researches have shown that their gene exhibit 79% of identical sequence and the receptor-binding domain structure is also very similar. There have been extensive research performed on SARS, however, the understanding of pathophysiology impact of Corona Virus Disease 2019(COVID-19) is still limited. In the review, we draw upon the lessons learnt from SARS in the epidemiology, clinical characteristics and pathogenesis for further understand the features of COVID-19. By comparing these two diseases, we found, COVID-19 has quicker and wider transmission, obvious family agglomeration, higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases were emerged in COVID-19. Children started with gastrointestinal symptoms may progress to severe condition and newborn whose mother was infected with COVID-19 could have severe complications. The laboratory test data showed, the percentage of neutrophils and the level of LDH is higher, otherwise the number of CD4+ and CD8+T cells is decreased in children's COVID-19 cases. Based on these early observations, as pediatrician, we put forward some thoughts on children's COVID-19 and give some recommendations to contain the disease.", "qid": 27, "docid": "b9unqnkb", "rank": 56, "score": 7.908100128173828}, {"content": "Title: From SARS to COVID-19: What we have learned about children infected with COVID-19 Content: Coronaviruses, both SARS-CoV and SARS-CoV-2 were firstly appeared in China. They have certain similarities in biological, epidemiological and pathological. To data, the researches have shown that their gene exhibit 79% of identical sequence and the receptor-binding domain structure is also very similar. There have been extensive research performed on SARS, however, the understanding of pathophysiology impact of Corona Virus Disease 2019(COVID-19) is still limited. In the review, we draw upon the lessons learnt from SARS in the epidemiology, clinical characteristics and pathogenesis for further understand the features of COVID-19. By comparing these two diseases, we found, COVID-19 has quicker and wider transmission, obvious family agglomeration, higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases were emerged in COVID-19. Children started with gastrointestinal symptoms may progress to severe condition and newborn whose mother was infected with COVID-19 could have severe complications. The laboratory test data showed, the percentage of neutrophils and the level of LDH is higher, otherwise the number of CD4+ and CD8+T cells is decreased in children's COVID-19 cases. Based on these early observations, as pediatrician, we put forward some thoughts on children's COVID-19 and give some recommendations to contain the disease.", "qid": 27, "docid": "lw935rii", "rank": 57, "score": 7.908099174499512}, {"content": "Title: Outcome of COVID-19 in liver transplant recipients: A preliminary report from Northwestern Italy Content: Covid-19 pandemic is deeply affecting transplant activity worldwide. It is unclear whether solid organ transplant recipients are at increased risk of developing severe complications and how they should be managed, also concerning immunosuppression. This is a report about the course and management of SARS-CoV-2 infection in liver transplant recipients from a single center in Northwestern Italy in the period March-April 2020. Three patients who were treated at our institution are reported in detail, whereas summary data are provided for those managed at peripheral Hospitals. Presentation varied from asymptomatic to rapidly progressive respiratory failure due to bilateral interstitial pneumonia. Accordingly, treatment and changes to immunosuppression were adapted to the severity of the disease. Overall mortality was 20%, whereas Covid-related mortality was 10%. Two cases of prolonged (>2 months) viral carriage were observed in two asymptomatic patients who contracted the infection in the early course after transplant. Besides depicting Covid-19 course and possible treatment scenarios in liver transplant patients, these cases are discussed in relation to the changes in our practice prompted by Covid-19 epidemic, with potential implications for other transplant programs.", "qid": 27, "docid": "0nhuxl45", "rank": 58, "score": 7.906400203704834}, {"content": "Title: Outcome of COVID\u201019 in liver transplant recipients: A preliminary report from Northwestern Italy Content: Covid\u201019 pandemic is deeply affecting transplant activity worldwide. It is unclear whether solid organ transplant recipients are at increased risk of developing severe complications and how they should be managed, also concerning immunosuppression. This is a report about the course and management of SARS\u2010CoV\u20102 infection in liver transplant recipients from a single center in Northwestern Italy in the period March\u2010April 2020. Three patients who were treated at our institution are reported in detail, whereas summary data are provided for those managed at peripheral Hospitals. Presentation varied from asymptomatic to rapidly progressive respiratory failure due to bilateral interstitial pneumonia. Accordingly, treatment and changes to immunosuppression were adapted to the severity of the disease. Overall mortality was 20%, whereas Covid\u2010related mortality was 10%. Two cases of prolonged (>2 months) viral carriage were observed in two asymptomatic patients who contracted the infection in the early course after transplant. Besides depicting Covid\u201019 course and possible treatment scenarios in liver transplant patients, these cases are discussed in relation to the changes in our practice prompted by Covid\u201019 epidemic, with potential implications for other transplant programs.", "qid": 27, "docid": "tmykgbyo", "rank": 59, "score": 7.906399250030518}, {"content": "Title: Coronaviruses: important emerging human pathogens. Content: The identification of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 reaffirmed the importance of understanding how coronaviruses emerge, infect, and cause disease. By comparing what is known about severe acute respiratory syndrome coronavirus (SARS-CoV) to what has recently been found for MERS-CoV, researchers are discovering similarities and differences that may be important for pathogenesis. Here we discuss what is known about each virus and what gaps remain in our understanding, especially concerning MERS-CoV.", "qid": 27, "docid": "inxp2qb4", "rank": 60, "score": 7.868500232696533}, {"content": "Title: A Letter to the Future AWWA Content: Dear Future AWWA Members, I'm writing to you on the 139th birthday of the American Water Works Association, and what a strange time it is We are in the midst of a global pandemic A disease called COVID\u201019 is spreading so quickly that we are running short on hospital beds and people are hoarding toilet paper At this moment, the United States has more confirmed cases than any other country and Canada is ranked 15th But I am not writing to tell you about the tragedy of COVID\u201019;I imagine the history books will capture that This is a letter about how today's water professionals are rising to the challenge through their selfless and often uncelebrated acts of courage They are building on the legacy of water professionals throughout AWWA's history, and I wish you were here to witness it As you\u2014the future AWWA\u2014look back on spring 2020, you will clearly see how access to safe, reliable water was critical in halting the spread of COVID\u201019 The simplest example I can provide is handwashing The practice of handwashing for at least 20 seconds, with plenty of soap, has never seemed so important Now, we are a society uniformly obsessed with washing our hands Because tap water is critical to personal hygiene and protecting the public's health, the US Environmental Protection Agency this week sent a letter to all governors, reminding them that water utility workers and water sector businesses that support water utilities should be considered \u201cessential\u201d as communities impose orders to keep people at home And in another sign of the essential nature of water service in a public health crisis, utilities are suspending water shutoffs and, in many cases, restoring service to customers who had previously been shut off But it isn't these policy decisions I hope you'll remember It's the exemplary\u2014and yes, courageous\u2014commitment of your predecessors in the water profession Each day, water professionals are delivering safe water to their communities and then cleaning the wastewater before returning it to the environment Never has this daily routine seemed more extraordinary These days, we are all being asked to participate in \u201csocial distancing,\u201d a term that most had never heard of before COVID\u201019 As schools and restaurants close and citizens are ordered to stay at home, your predecessors in the water profession continue to do what it takes to keep the water flowing, whether that is repairing mains, unclogging sewer lines (you can't imagine what some people do in the absence of toilet paper!), or ensuring treatment equipment is functioning properly Many water professionals are stationed 24/7 at treatment plants They are living apart from their own families so they can protect all of our families The ongoing pandemic has given our society new appreciation for the work of health professionals, police, and other first responders I would say that water professionals are not only first responders, but \u201ceveryday\u201d responders They are the super\u2010heroes we don't need to summon because they are already on the scene I am certain that in time we will be able to return to a more normal state, where a handshake is a handshake and not an elbow bump And when we do, I hope that we\u2014and the people who live in the communities we serve\u2014remember that water is critical to everything we care about and that it played a crucial role in eliminating COVID\u201019 It is not an overstatement to say that others\u2019 lives were in the hands of water professionals during the pandemic Poet and philosopher George Santayana is known for saying, \u201cThose who cannot remember the past are condemned to repeat it \u201d In this case, however, it would be wise to remember and repeat selfless acts like those of water professionals facing COVID\u201019 in the spring of 2020 In closing, Happy Birthday, AWWA, and my thanks to all who are members today and in the future Your commitment to the legacy of safe and reliable water service is, quite literally, life\u2010saving Sincerely, David B LaFrance Chief Executive Officer, American Water orks Association", "qid": 27, "docid": "sk86rbap", "rank": 61, "score": 7.861100196838379}, {"content": "Title: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes Content: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it\u2019s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven\u2019t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don\u2019t yet know what the real-life significance of this variation is, but it\u2019s possible that these variants decrease the protein\u2019s ability to interact with the SARS-CoV-2 virus, thus decreasing the person\u2019s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.", "qid": 27, "docid": "p7drekee", "rank": 62, "score": 7.859000205993652}, {"content": "Title: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Content: In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19-infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.", "qid": 27, "docid": "ifu4fvwh", "rank": 63, "score": 7.852200031280518}, {"content": "Title: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Content: Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19\u2013infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.", "qid": 27, "docid": "rvg5elrc", "rank": 64, "score": 7.852199077606201}, {"content": "Title: Characterization of an asymptomatic cohort of SARS-COV-2 infected individuals outside of Wuhan, China Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, resulting in the coronavirus disease COVID-19) is highly transmissible among people. Asymptomatic infections are also an important source of infection. Here, we aimed to further clarify the epidemiologic and clinical characteristics of asymptomatic SARS-CoV-2 infections. METHODS: We identified close contacts of confirmed COVID-19 cases in northeast Chongqing who were RT-PCR+ yet remained asymptomatic throughout their infections. We stratified this cohort by normal versus abnormal findings on chest CT, and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors. RESULTS: Between January and March, 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. Of these, 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days (range 1 to 29), and 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (p < 0.05). Nine subjects (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of nucleic acid turning negative in asymptomatic COVID-19 patients was 13 days, compared to 10.4 days in those with normal chest CT (p < 0.05). CONCLUSIONS: A portion of these asymptomatic individuals, with and without abnormal chest CT scans, were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment on asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken.", "qid": 27, "docid": "we4kfb8u", "rank": 65, "score": 7.848199844360352}, {"content": "Title: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known? Content: Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.", "qid": 27, "docid": "tojgojjf", "rank": 66, "score": 7.828700065612793}, {"content": "Title: On the evolutionary epidemiology of SARS-CoV-2 Content: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.", "qid": 27, "docid": "ig0rnbqb", "rank": 67, "score": 7.822299957275391}, {"content": "Title: Thinking about \u201cThinking about COVID-19\u201d Content: Only three months after its emergence, that tiny virus is changing the values and behavior of human race In order to protect ourselves, not only about \"experts\" such as scientists and politicians, but also about ordinary people have to think about it So, what kind of information do we need? What are the issues and controversy? I would like to think about how to make an article called \"Thinking about COVID-19\" as an example of science communication At this time, it would be useful to look back on SARS I hope that this paper will be useful not only for science communicators who write articles, but also for those who want to think more broadly about how to grasp and consider the problems posed by reality and how to communicate science and technology by taking a meta-view of the problems and their treatment I readily welcome any suggestions or criticisms", "qid": 27, "docid": "55ngu8y3", "rank": 68, "score": 7.820700168609619}, {"content": "Title: The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles Content: Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.", "qid": 27, "docid": "m4k20i7g", "rank": 69, "score": 7.811999797821045}, {"content": "Title: Point-of-care lung ultrasound in three neonates with COVID-19 Content: Since March 2020, the world is involved in the COVID-19 pandemic, a disease caused by a novel virus called SARS-CoV-2. Some authors have described the ultrasonographic findings of COVID-19 pneumonia in adults and children, but data on neonates are lacking. Our objective was to describe the ultrasonographic lung pattern on newborns with SARS-CoV-2 infection during the COVID-19 pandemic. Newborns who tested positive for SARS-CoV-2 PCR in respiratory samples and were evaluated with point-of-care lung ultrasound (LU) from March to April 2020 were included. LU was performed bedside by a single investigator at the time of diagnosis and every 48 h during the first week following diagnosis. Six areas were studied. Three neonates were included. Infants' comorbidities included meconium aspiration syndrome, bronchopulmonary dysplasia, and Hirschsprung's disease. One required mechanical ventilation. No deaths occurred. LU showed B-lines, consolidation, and spared areas. No pneumothorax or pleural effusion was observedConclusions: LU could be of value when managing COVID-19 neonates. We describe the findings of lung ultrasound monitoring during the first week following diagnosis in three neonates with SARS-CoV-2 infection. What is known: \u00e2\u0080\u00a2 Lung ultrasound (LU) is a useful tool in COVID-19 management in adults. To date, no report on LU and neonates with SARS-CoV-2 infection has been published. What is new: \u00e2\u0080\u00a2 This study adds evidence about LU findings in neonates with SARS-CoV-2 infection.", "qid": 27, "docid": "pab56xyd", "rank": 70, "score": 7.794899940490723}, {"content": "Title: EFFECTS OF COVID-19 INFECTION DURING PREGNANCY AND NEONATAL PROGNOSIS: WHAT IS THE EVIDENCE? Content: Background: Little is known about how COVID-19 infection affects pregnant women, as well as about the possibility of vertical transmission or that of premature labor. Thus, this studys objective was to identify existing evidence to directive public policies. Method: Systematic literature review assessing papers published in the most comprehensive databases in the field of health. Results: 12 papers were eligible. A total of 119 pregnant women aged between 22 and 42 years old and between the 12th and 41st weeks were analyzed; 90 children were born. Most pregnant women acquired the infection in the third trimester of pregnancy, 97.4% were diagnosed before hospitalization based on signs and symptoms. There was no maternal death and no vertical transmission was confirmed. Conclusions: pregnant women must be cautious and vigilant because their exposure to the virus, even if at the end of a pregnancy, has important repercussions, especially for the type of labor.", "qid": 27, "docid": "fvzkxetl", "rank": 71, "score": 7.79040002822876}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10\u201320% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 27, "docid": "2ootfjhk", "rank": 72, "score": 7.787799835205078}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 27, "docid": "88n6hwyo", "rank": 73, "score": 7.787798881530762}, {"content": "Title: Cytokine storm and the prospects for immunotherapy with COVID-19. Content: Knowledge about the pathobiology of SARS-COV-2 as it interacts with immune defenses is limited. SARS-COV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 3 stages: asymptomatic-paucisymptomatic incubation, nonsevere symptomatic illness for 80% of those infected, and severe respiratory illness. A syndrome characterized by hypercytokinemic inflammation referred to as a \"cytokine storm\" can occur in patients with advanced disease. Effective antiviral agents that can prevent viral infection in exposed individuals are needed.", "qid": 27, "docid": "2skjqwis", "rank": 74, "score": 7.767000198364258}, {"content": "Title: Cytokine storm and the prospects for immunotherapy with COVID-19 Content: Knowledge about the pathobiology of SARS-COV-2 as it interacts with immune defenses is limited. SARS-COV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 3 stages: asymptomatic-paucisymptomatic incubation, nonsevere symptomatic illness for 80% of those infected, and severe respiratory illness. A syndrome characterized by hypercytokinemic inflammation referred to as a \"cytokine storm\" can occur in patients with advanced disease. Effective antiviral agents that can prevent viral infection in exposed individuals are needed.", "qid": 27, "docid": "dd836h0r", "rank": 75, "score": 7.766999244689941}, {"content": "Title: COVID-19 and the difficulty of inferring epidemiological parameters from clinical data Content: Knowing the infection fatality ratio (IFR) is of crucial importance for evidence-based epidemic management: for immediate planning; for balancing the life years saved against the life years lost due to the consequences of management; and for evaluating the ethical issues associated with the tacit willingness to pay substantially more for life years lost to the epidemic, than for those to other diseases. Against this background Verity et al. (2020, Lancet Infections Diseases) have rapidly assembled case data and used statistical modelling to infer the IFR for COVID-19. We have attempted an in-depth statistical review of their approach, to identify to what extent the data are sufficiently informative about the IFR to play a greater role than the modelling assumptions, and have tried to identify those assumptions that appear to play a key role. Given the difficulties with other data sources, we provide a crude alternative analysis based on the Diamond Princess Cruise ship data and case data from China, and argue that, given the data problems, modelling of clinical data to obtain the IFR can only be a stop-gap measure. What is needed is near direct measurement of epidemic size by PCR and/or antibody testing of random samples of the at risk population.", "qid": 27, "docid": "cyjfljoa", "rank": 76, "score": 7.754000186920166}, {"content": "Title: What We Learned about COVID-19 So Far? Notes from Underground Content: The novel coronavirus pandemic poses a major global threat to public health. Our knowledge concerning every aspect of COVID-19 is evolving rapidly, given the increasing data from all over the world. In this narrative review, the Turkish Thoracic Society Early Career Taskforce members aimed to provide a summary on recent literature regarding epidemiology, clinical findings, diagnosis, treatment, prevention, and control of COVID-19. Studies revealed that the genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Angiotensin-converting enzyme 2 receptor is an important target of the SARS-CoV-2 while entering an organism. Smokers were more likely to develop the disease and have a higher risk for ICU admission. The mean incubation period was 6.4 days, whereas asymptomatic transmission was reported up to 25 days after infection. Fever and cough were the most common symptoms, and cardiovascular diseases and hypertension were reported to be the most common comorbidities among patients. Clinical manifestations range from asymptomatic and mild disease to severe acute respiratory distress syndrome. Several patients showed typical symptoms and radiological changes with negative RT-PCR but positive IgG and IgM antibodies. Although radiological findings may vary, bilateral, peripherally distributed, ground-glass opacities were typical of COVID-19. Poor prognosis was associated with older age, higher Sequential Organ Failure Assessment score, and high D-dimer level. Chloroquine was found to be effective in reducing viral replication in vitro. Likewise, protease inhibitors, including lopinavir/ritonavir, favipiravir, and nucleoside analogue remdesivir were proposed to be the potential drug candidates in COVID-19 management. Despite these efforts, we still have much to learn regarding the transmission, treatment, and prevention of COVID-19.", "qid": 27, "docid": "8n4cnfiw", "rank": 77, "score": 7.741499900817871}, {"content": "Title: What We Learned about COVID-19 So Far? Notes from Underground. Content: The novel coronavirus pandemic poses a major global threat to public health. Our knowledge concerning every aspect of COVID-19 is evolving rapidly, given the increasing data from all over the world. In this narrative review, the Turkish Thoracic Society Early Career Taskforce members aimed to provide a summary on recent literature regarding epidemiology, clinical findings, diagnosis, treatment, prevention, and control of COVID-19. Studies revealed that the genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Angiotensin-converting enzyme 2 receptor is an important target of the SARS-CoV-2 while entering an organism. Smokers were more likely to develop the disease and have a higher risk for ICU admission. The mean incubation period was 6.4 days, whereas asymptomatic transmission was reported up to 25 days after infection. Fever and cough were the most common symptoms, and cardiovascular diseases and hypertension were reported to be the most common comorbidities among patients. Clinical manifestations range from asymptomatic and mild disease to severe acute respiratory distress syndrome. Several patients showed typical symptoms and radiological changes with negative RT-PCR but positive IgG and IgM antibodies. Although radiological findings may vary, bilateral, peripherally distributed, ground-glass opacities were typical of COVID-19. Poor prognosis was associated with older age, higher Sequential Organ Failure Assessment score, and high D-dimer level. Chloroquine was found to be effective in reducing viral replication in vitro. Likewise, protease inhibitors, including lopinavir/ritonavir, favipiravir, and nucleoside analogue remdesivir were proposed to be the potential drug candidates in COVID-19 management. Despite these efforts, we still have much to learn regarding the transmission, treatment, and prevention of COVID-19.", "qid": 27, "docid": "p0fwmnn3", "rank": 78, "score": 7.741498947143555}, {"content": "Title: A cluster of COVID-19 in pilgrims to Israel Content: This report describes a cluster of SARS-CoV-2 infections in pilgrims returning from Israel to Greece. Out of 53 pilgrims, 48 (90.5%) were tested positive for SARS-CoV-2; of them, 41 (85.4%) developed symptoms consistent with COVID-19, and 7 (14.6%) remained asymptomatic. These cases suggest a high risk of COVID-19 infection for pilgrims traveling during the pandemic. Although at that time the prevalence of the disease was low in the origin and destination countries, crowded exposure to other pilgrims from many other countries led to this cluster. Increasing awareness about the risks in pilgrims is important and particularly for elderly pilgrims and those with underlying conditions.", "qid": 27, "docid": "qcy7bb5z", "rank": 79, "score": 7.741099834442139}, {"content": "Title: [Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies]. Content: The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing a possible epidemic rebound. This review describes and defines the COVID-19 asymptomatic carrier state and outlines methods for identifying counting and reporting these cases. The author elaborates that the asymptomatic carrier state can be further divided into asymptomatic infection and pre-symptomatic infection after extended follow-up based on the nature of disease progression. The author presents the limited available data about infectiousness of asymptomatic and pre-symptomatic cases and their possible contributions to the overall epidemic of COVID-19 observed so far in China. Challenges of a possible second epidemic wave of COVID-19 caused by asymptomatic and pre-symptomatic cases are discussed and suggestions for control strategies and scientific research are provided.", "qid": 27, "docid": "ghasrwqc", "rank": 80, "score": 7.737400054931641}, {"content": "Title: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Content: The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).", "qid": 27, "docid": "7q9jady4", "rank": 81, "score": 7.735099792480469}, {"content": "Title: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Content: Abstract The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).", "qid": 27, "docid": "vhtc0jvq", "rank": 82, "score": 7.735098838806152}, {"content": "Title: Cytokine storm and the prospects for immunotherapy with COVID-19 Content: Knowledge about the pathobiology of SARS-CoV-2 as it interacts with immune defenses is limited. SARS-CoV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 2 or 3 stages: most patients who recover experience 2 stages of illness commencing with an asymptomatic or paucisymptomatic incubation period, followed by a nonsevere symptomatic illness lasting for several weeks, occurring in about 80% of those infected. In the remainder, a third phase marked by a severe respiratory illness, often accompanied by multisystem dysfunction, coagulopathy, and shock is observed. This phase of the illness is characterized by hypercytokinemic inflammation and is often referred to as \"cytokine storm.\" While the immunopathogenesis remains unclear, prospects of treating this severe phase of the illness with immunotherapy are evolving, with some treatments showing promise.", "qid": 27, "docid": "be38b41o", "rank": 83, "score": 7.727700233459473}, {"content": "Title: Detection of respiratory viruses in gargle specimens of healthy children Content: Abstract Background Respiratory tract viral infection is one of the most common and important diseases in children. Polymerase chain reaction (PCR) tests are often used to detect viruses in samples, it is difficult to interpret the clinical significance of PCR positivity, which may reflect a past, imminent or active asymptomatic infection due to their high sensitivity. Although single respiratory viruses have been detected in samples from children with symptoms, other respiratory viruses can also be detected simultaneously. However, the clinical importance of these findings for the symptoms is not known. Objectives To investigate the prevalence of respiratory viruses among children without any symptoms such as acute respiratory illness and/or fever. Study design From week twenty-five 2013 to week twenty-six 2014, gargle samples were collected from children once a week and these samples were subjected to real-time PCR to detect respiratory viruses. On each sampling day, we asked the parents about their children\u2019s health condition. Results Among the 286 samples collected, 200 were from asymptomatic children. In the asymptomatic condition, human parechovirus, adenovirus, enterovirus, rhinovirus, coronavirus 229E and HKU1 were observed in 45 episodes. In samples from symptomatic children, parainfluenza viruses, respiratory syncytial virus and coronavirus OC43 were detected in addition to those mentioned above. Conclusions Various viruses of different species were detected in the specimens from the children regardless of their health status. It might be speculated that host factors such as the function of the immune system influence the clinical outcome of the infection. However, this needs to be studied further.", "qid": 27, "docid": "8homqmux", "rank": 84, "score": 7.716899871826172}, {"content": "Title: Use of systemic therapies for psoriasis in the COVID-19 era. Content: BACKGROUND In late 2019 a viral pneumonia began to spread across the world. The viral disease, COVID-19, is now officially a pandemic, causing concern for the potential risk of systemic therapies for patients with psoriasis. OBJECTIVE The purpose of this review is to analyze what is currently known about COVID-19 in regard to the safety of systemic treatment, and to provide guidelines for use in psoriasis during this pandemic. METHODS Review of guidelines from various dermatologic regulatory bodies regarding the use of systemic medications during the COVID-19 pandemic was performed and summarized. RESULTS The AAD,NPF and IPC are in agreement regarding their recommendation that patients with active COVID-19 infection should discontinue any biologic therapy. CONCLUSION Patients with active COVID-19 infections should discontinue systemic treatment for psoriasis. Patients with risk factors should discuss continuing treatment on a case by case basis.", "qid": 27, "docid": "wyln1jpr", "rank": 85, "score": 7.711100101470947}, {"content": "Title: Use of systemic therapies for psoriasis in the COVID-19 era Content: BACKGROUND: In late 2019 a viral pneumonia began to spread across the world. The viral disease, COVID-19, is now officially a pandemic, causing concern for the potential risk of systemic therapies for patients with psoriasis. OBJECTIVE: The purpose of this review is to analyze what is currently known about COVID-19 in regard to the safety of systemic treatment, and to provide guidelines for use in psoriasis during this pandemic. METHODS: Review of guidelines from various dermatologic regulatory bodies regarding the use of systemic medications during the COVID-19 pandemic was performed and summarized. RESULTS: The AAD,NPF and IPC are in agreement regarding their recommendation that patients with active COVID-19 infection should discontinue any biologic therapy. CONCLUSION: Patients with active COVID-19 infections should discontinue systemic treatment for psoriasis. Patients with risk factors should discuss continuing treatment on a case by case basis.", "qid": 27, "docid": "xp5lvnbp", "rank": 86, "score": 7.711099147796631}, {"content": "Title: COVID-19: asymptomatic carrier transmission is an underestimated problem Content: At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R0), effective reproduction number (Rt) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R0, Rt and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "qid": 27, "docid": "32jaz3vz", "rank": 87, "score": 7.7032999992370605}, {"content": "Title: Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China Dong Y, Mo X, Hu Y, et al. Pediatrics. 2020; doi: 10.1542/peds.2020-0702. Content: Novel coronavirus (SARS-CoV-2, which causes COVID-19) is a pandemic with many countries employing massive public health responses. Little is known about the severity of illness in the pediatric population. This study sought to identify demographic information and severity of disease in pediatric patients with COVID-19. This was a retrospective study conducted on patients less than 18 years who were suspected or confirmed to have COVID-19 and were reported to the Chinese Centers for Disease Control (China CDC). Children were considered high risk and suspected if they had positive exposure to an endemic area or a confirmed case of COVID-19. High suspicion also included those with fever, respiratory symptoms, digestive symptoms, or fatigue, normal or low white blood cell count and increased C-reactive protein, or abnormal chest radiography, or those at lower risk for whom influenza or other respiratory illnesses were ruled out. Confirmed cases were defined as having a nasopharyngeal swab or blood sample positive via PCR or a genetic sampling of respiratory secretions or blood consistent with SARS-CoV-2. Once identified, patients were categorized by severity of disease using clinical features as well as laboratory and radiographic findings. Severity categories included asymptomatic (no symptoms but positive test), mild (mild respiratory symptoms and normal lung exam), moderate (pneumonia, fever, and cough but without hypoxemia or respiratory distress), severe (above symptoms as well as oxygen saturation less than 92% and respiratory distress), or critical disease (acute respiratory failure, acute respiratory distress syndrome, shock, or other life-threatening organ dysfunction). There were 2143 patients included who were suspected (65.9%) or confirmed (34.1%) to have COVID-19. Median age was 7 years (IQR 2-13) and the majority (56.6%) were male. The median time from onset of symptoms to presentation was 2 days (range 0-42). Nearly all were categorized as asymptomatic (4.4%), mild (50.9%), or moderate (38.8%) severity, leaving only 5.9% as severe or critical. Looking at breakdown by age, infants made up the highest proportion of severe or critical disease (32%) with preschool ages (1-5 years) next with 28.8%. Half (7) of the 13 critical patients were under 1 year old. No significant differences were seen between male or female patients. There was one death in the sample: a 14-year old boy. Limitations included lack of clinical characteristics, as only data from the Chinese CDC was used rather than electronic medical records from individual patients. Additionally the majority of cases were suspected, not confirmed, and some of the children remained hospitalized at the end of the study therefore severity of disease may not be accurate. The authors concluded that COVID-19 caused infection in all ages without obvious gender differences, however younger children appeared to have higher severity of disease. Comment: This is the largest cohort of pediatric COVID-19 patients to date. This study is based on the China CDC dataset and is limited to the variables that are reported to the CDC. We cannot assume children in the United States will be affected similarly. Overall, this dataset suggests that critical disease is rare in children with COVID-19. Emergency physicians should use caution with infants and young children, however, as they appear to be at highest risk of severe disease and may need closer observation in the emergency department or inpatient admission.", "qid": 27, "docid": "h93g5hvf", "rank": 88, "score": 7.6956000328063965}, {"content": "Title: Middle East respiratory syndrome coronavirus in healthcare settings. Content: PURPOSE OF REVIEW Attracting global attention, Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause sporadic cases and a potential risk of healthcare-associated infections. In this review, we highlight what is known about the risk of transmission within healthcare facilities and discuss interventions to halt its transmission within healthcare. RECENT FINDINGS MERS-CoV causes a wide range of infections from asymptomatic infections, mild or moderately symptomatic cases, to fatal disease. Two years after the initial reported case, MERS-CoV has caused limited disease outside the Arabian Peninsula with several cases in Europe, Asia, and the United States. Epidemiologically, these infections are linked to exposures from the region and their diagnosis outside is related to travel. Several reported clusters of disease report multiple transmissions of MERS-CoV within healthcare settings that have been attributed to poor compliance with the basic infection control measures. Factors contributing to the spread and control of MERS-CoV within healthcare settings have not been elucidated so far. Data suggest the overcrowding, late recognition of MERS-CoV cases, and inadequate infection control practices contribute significantly to the transmission. SUMMARY Understanding factors contributing to the spread and the dynamic of MERS-CoV transmission within healthcare settings would further enhance the control of the disease in and outside the healthcare setting.", "qid": 27, "docid": "a7hsppj1", "rank": 89, "score": 7.685299873352051}, {"content": "Title: General Surgery Operating Room Practice in Patients with COVID-19 Content: The virus COVID-19, which emerged in China in December 2019, was announced by the World Health Organization as a pandemic in January 2020 It is known that infection is not severe and may even progress without symptoms in patients who have come into contact with COVID-19 Although various organizations have been informed about how to take measures to protect the patient and the surgeon in case of diseases requiring urgent or elective surgery in people infected with COVID-19 or in cases with high suspicion, there is still no definite judgment between patients, physicians and health authorities In this study, which was prepared with the initiative of the Turkish Surgical Association, we tried to shed light on what should be done and how surgeons should act in patients whose operation is mandatory in light of the available data", "qid": 27, "docid": "lsse2xvw", "rank": 90, "score": 7.6828999519348145}, {"content": "Title: COVID-19: asymptomatic carrier transmission is an underestimated problem Content: At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R(0)), effective reproduction number (R(t)) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R(0), R(t) and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "qid": 27, "docid": "c93j35fl", "rank": 91, "score": 7.663700103759766}, {"content": "Title: Prevalence of SARS-CoV-2 infection among asymptomatic healthcare workers in greater Houston: a cross-sectional analysis of surveillance data from a large healthcare system Content: Objective: To determine the prevalence of SARS-CoV-2 infection among asymptomatic COVID-19 facing and non-COVID-19 facing Healthcare Workers (HCWs), with varying job categories across different hospitals. Design: Cross-sectional analysis of a healthcare system surveillance program that included asymptomatic clinical (COVID-19 facing and non-COVID-19 facing), and non-clinical HCWs. A convenience sample of asymptomatic community residents (CR) was also tested. Proportions and 95% confidence intervals (CI) of SARS-CoV-2 positive HCWs are reported. Proportional trend across HCW categories was tested using Chi Square trend test. Logistic regression model-based likelihood estimates of SARS-CoV-2 prevalence among HCWs with varying job functions and across different hospitals are reported as adjusted odds ratios (aOR) and CI. Setting: Healthcare system comprising one tertiary care academic medical center and six large community hospitals across Greater Houston and a community sample. Participants: 2,872 self-reported asymptomatic adult (> 18 years) HCWs and CRs. Exposure: Clinical HCWs in COVID-19 and non-COVID-19 units, non-Clinical HCWs, and CRs. Job categories of Nursing, Providers, Allied Health, Support, and Administration / Research. Seven hospitals in the healthcare system. Main Outcomes: Positive reverse transcriptase polymerized chain reaction (RT-PCR) test for SARS-CoV-2 Results: Among 2,872 asymptomatic HCWs and CRs, 3.9% (CI: 3.2 - 4.7) tested positive for SARS-CoV-2. Mean (SD) age was 40.9 (11.7) years and 73% were females. Among COVID-19 facing HCWs 5.4% (CI: 4.5 - 6.5) were positive, whereas 0.6% (CI: 0.2 - 1.7%) of non COVID-19 facing HCWs and none of the non-clinical HCWs or CRs were positive (Ptrend < 0.001). Among COVID-19 facing HCWs, SARS-CoV-2 positivity was similar for all job categories (p = 0.74). However, significant differences in positivity were observed across hospitals. Conclusions and Relevance: Asymptomatic HCWs with COVID-19 patient exposure had a higher rate of SARS-CoV-2 positive testing than those not routinely exposed to COVID-19 patients and those not engaged in patient care. Among HCWs with routine COVID-19 exposure, all job types had relatively similar infection rates. These data can inform hospital surveillance and infection control practices for patient-facing job classifications and suggest that general environmental exposure within hospitals is not a significant source of asymptomatic SARS-CoV-2 infection.", "qid": 27, "docid": "cib1oivu", "rank": 92, "score": 7.662799835205078}, {"content": "Title: Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population Shows Low Rates of Positivity Content: Introduction Seattle region hospitals have been severely impacted for several months by ongoing community spread of the novel coronavirus 2019 disease. (1,2) Although testing was initially focused on the diagnosis and treatment of symptomatic patients, this effort has now expanded to include surveillance of asymptomatic patients in order to protect health care workers and prevent nosocomial infections. There is an urgent need to understand best practices for the delivery of routine medical care during an ongoing outbreak. (3) Here we report the rates of SARS-CoV-2 infection in asymptomatic patients screened prior to admission or a surgical or aerosolizing procedure. Methods Beginning March 30, 2020, our hospital began screening all asymptomatic patients prior to needed surgeries and aerosolizing procedures (n=350). On April 13, 2020, we expanded this practice to universal surveillance screening of all patients prior to admission (n=349). Testing was performed on nasopharyngeal swabs using the Washington state emergency use authorized University of Washington CDC-based laboratory-developed test or FDA authorized DiaSorin Simplexa SARS-CoV-2, Hologic Panther Fusion SARS-CoV-2, or Roche cobas SARS-CoV-2 tests. This study was approved by the Institutional Review Board of University of Washington Medical Center (STUDY00009734). Informed consent was not required. Results For patients undergoing surgical or aerosolizing procedures, 3 of 350 patients (0.9%) were positive for SARS-CoV-2. For patients who were asymptomatic and tested at the time of admission, 3 of 349 patients (0.9%) were positive and 2 of 349 (0.6%) were inconclusive; inconclusive results were treated as low-level positives. For asymptomatic patients tested for any other reason (e.g. exposure risk), 12 of 157 patients (7.6%) were positive and 1 of 157 (0.6%) were inconclusive. Meanwhile, of the 473 inpatients in this period who had any symptom concerning for COVID-19, 68 of 473 patients (14.3%) were positive. There was a variety of ordering services and locations in all indication categories, with no particular predominating medical service or location. During this time period the outpatient prevalence of SARS-CoV-2 active infection in our region was 3-5% (manuscript in review). Discussion The application of universal surveillance testing for SARS-CoV-2 in patients prior to surgery or aerosolizing procedure shows that the positivity rate for SARS-CoV-2 is low (<1%) in asymptomatic patients without known exposure risk factors. The positivity rate for asymptomatic patients on admission screen was similar; both measures were notably lower than recently reported measurements during an outbreak in New York City that found a positivity rate of 13.7% in asymptomatic pregnant women. (4) The rate of sub-clinical infection likely varies with the scale of the community outbreak. Even in the context of a community-wide outbreak, our data show a low prevalence of COVID-19 infection in the urgent pre-procedural setting. These data reflect the prevalence of asymptomatic SARS-CoV-2 infection in a population of individuals who use medical services and provide an assessment of exposure risk to other patients and healthcare workers around the time of admission. The Greater Seattle Coronavirus Assessment Network (SCAN) also recently published results from the first 18 days of home-based testing and reported no positive tests in 1392 patients reporting no COVID-19-like illness. (5) Although other studies support a large proportion of asymptomatic infections, the data from this metropolitan outbreak do not support a similar pattern. Clinical providers, especially those involved in performing procedures that have a risk of aerosolization, are asking for methods to risk-assess patients prior to the procedure. Pre-procedure testing is one option to accomplish this goal. Importantly, in the midst of an outbreak, testing prior to procedures can decrease the use of PPE, identify appropriate precautions for patients, and reduce the risk of nosocomial infection.", "qid": 27, "docid": "9hvhru6o", "rank": 93, "score": 7.63539981842041}, {"content": "Title: COVID-19 in Children: An Ample Review Content: The aim of this review was to describe the current knowledge about coronavirus disease 2019 (COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in children, from epidemiological, clinical, and laboratory perspectives, including knowledge on the disease course, treatment, and prognosis. An extensive literature search was performed to identify papers on COVID-19 (SARS-CoV-2 infection) in children, published between January 1, 2020 and April 1, 2020. There were 44 relevant papers on COVID-19 in children. The results showed that COVID-19 occurs in 0.39\u201312.3% of children. Clinical signs and symptoms are comparable to those in adults, but milder forms and a large percentage of asymptomatic carriers are found among children. Elevated inflammatory markers are associated with complications and linked to various co-infections. Chest computed tomography (CT) scans in children revealed structural changes similar to those found in adults, with consolidations surrounded by halos being somewhat specific for children with COVID-19. The recommended treatment includes providing symptomatic therapy, with no specific drug recommendations for children. The prognosis is much better for children compared to adults. This review highlights that COVID-19 in children is similar to the disease in the adult population, but with particularities regarding clinical manifestations, laboratory test results, chest imaging, and treatment. The prognosis is much better for children compared to adults, but with the progression of the pandemic; the cases in children might change in the future.", "qid": 27, "docid": "8du0s33p", "rank": 94, "score": 7.587399959564209}, {"content": "Title: A Systematic Review of Cases of Acute Respiratory Distress Syndrome in the Coronavirus Disease 2019 Pandemic Content: The outbreak of coronavirus disease 2019 (COVID-19) was declared a global pandemic after it spread to 213 countries and has the highest total number of cases worldwide. About 80% of COVID-19 infections are mild or asymptomatic and never require hospitalization but about 5% of patients become critically ill and develop acute respiratory distress syndrome (ARDS). The widely used management for ARDS in COVID-19 has been in line with the standard approach, but the need to adjust the treatment protocols has been questioned based on the reports of higher mortality risk among those requiring mechanical ventilation. \ufeffTreatment options for this widespread disease are limited and there are no definitive therapies or vaccines until now. Although some antimalarial and antiviral drugs may prove effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their safety and efficacy are still under clinical trials. We conducted a systematic review of case reports on ARDS in SARS-CoV-2 infection to summarize the clinical presentation, laboratory and chest imaging findings, management protocols, and outcome of ARDS in COVID-19-positive patients. We need \ufeffmore data and established studies for the effective management of the novel SARS-CoV-2 and to reduce mortality in high-risk patients.", "qid": 27, "docid": "u2gm3kyh", "rank": 95, "score": 7.587399005889893}, {"content": "Title: Immunological determinants of clinical outcomes in COVID-19: A quantitative perspective Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical presentation that ranges from asymptomatic, to severe disease with cytokine storm. The mortality rates also differ across the globe, ranging from 0.5-13%. This variation is likely due to both pathogen and host factors. Host factors may include genetic differences in the immune response genes as well as variation in HLA and KIR allotypes. To better understand what impact these genetic variants in immune response genes may have in the differences observed in the immune response to SARS-CoV-2, a quantitative analysis of a dynamical systems model that considers both, the magnitude of viral growth, and the subsequent innate and adaptive response required to achieve control of infection is considered. Based on this broad quantitative framework it may be posited that the spectrum of symptomatic to severely symptomatic presentations of COVID19 represents the balance between innate and adaptive immune responses. In asymptomatic patients, prompt and adequate adaptive immune response quells infection, whereas in those with severe symptoms a slower inadequate adaptive response leads to a runaway cytokine cascade fueled by ongoing viral replication. Polymorphisms in the various components of the innate and adaptive immune response may cause altered immune response kinetics that would result in variable severity of illness. Understanding how this genetic variation may alter the response to SARS-CoV-2 infection is critical to develop successful treatment strategies.", "qid": 27, "docid": "zc7u3g34", "rank": 96, "score": 7.584199905395508}, {"content": "Title: Organ donation during the coronavirus pandemic: an evolving saga in uncharted waters Content: Coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic of respiratory illness, known as coronavirus disease 2019 (COVID-19).[1] The risk of developing COVID-19 from a SARS-CoV-2 infected organ donor is unknown. Therefore, extreme caution is necessary when considering transplantation. Transmission is affected by epidemiological risk factors, incubation period, degree of viraemia, and viability of SARS-CoV-2 in blood and organ compartments. Recent guidelines from NHSBT[2] recommend that all potential donors be tested for SARS-CoV-2 and donation suspended from those who test positive. Donation is discouraged for asymptomatic individuals who have been in a COVID-19-affected area in the last 28 days.", "qid": 27, "docid": "rdzeja13", "rank": 97, "score": 7.584000110626221}, {"content": "Title: Near-term pregnant women's attitude toward, concern about and knowledge of the COVID-19 pandemic. Content: Background: COVID-19 is a novel type of the coronavirus family with an incompletely described clinical course. Little is known about the psychological aspects, particularly for vulnerable populations including pregnant women.Objectives: To understand the attitude, concerns, and knowledge of the non-infected pregnant women toward the COVID-19 outbreak in order to constitute base data for detailed counseling and to develop targeted messages.Patients and methods: This cross-sectional survey research presented analysis of prospectively collected data yielded at a single tertiary \"Coronavirus Pandemic Hospital\" referral center for a ten days period following the first confirmed death due to the COVID-19 pandemic in Turkey. Non-infected women with a confirmed pregnancy over 30th gestational week were consecutively included. A patient-reported non-validated questionnaire formed by the expert committee that includes 15 specific questions was used. Non-infected, pregnant women over 30th gestational week who applied to the outpatient clinic were consecutively included. A total of 213 women were enrolled, 37 were excluded: 7 for being in the first trimester, 3 were illiterate, and 27 were Syrian refugees having difficulties in translation.Results: A total of 172 pregnant women were included. Overall, four women refused to participate to the survey (1.9%). The mean age was 27.5 \u00b1 5.3 years. Median gestational week and parity were 35 \u00b1 11 weeks and 1 \u00b1 2, respectively. Pregnant women were observed to trust the authorities (65%) and the healthcare staff (92.4%), and their respect was increased (82.5%) during the outbreak. Majority of the women (87.2%) comply with the self-quarantine rules. Half of the women (52%) reported that they felt vulnerable and predominantly were concerned (80%). Approximately one-third of the women constantly keep thinking that they may get infected (35.5%) or they might get infected during/following the delivery or their baby might get infected after being born (42%). Half of the women (50%) were reported that they either had no idea about or think the breastfeeding is not safe during the outbreak. About 45% of the women were confused or had doubts about if the mode of delivery may be affected by the pandemic. Greater part of the participants does not know if COVID-19 might cause birth defects (76%) or preterm birth (64.5%). Counseling flow keys helping pregnant women to overcome misleads, regarding the COVID-19 outbreak is proposed.Conclusions: Non-infected pregnant women with a viable pregnancy at near term were observed to have positive attitude and compliance toward the COVID-19 outbreak and frontline healthcare staff; increased concern and vulnerability; and restricted knowledge about the pregnancy-related outcomes. While the clinical evidence was growing rapidly, this data may guide obstetricians and midwives to perceive what accurate information should be provided to the pregnant women.", "qid": 27, "docid": "f93porms", "rank": 98, "score": 7.582900047302246}, {"content": "Title: Near-term pregnant women's attitude toward, concern about and knowledge of the COVID-19 pandemic Content: Background: COVID-19 is a novel type of the coronavirus family with an incompletely described clinical course. Little is known about the psychological aspects, particularly for vulnerable populations including pregnant women.Objectives: To understand the attitude, concerns, and knowledge of the non-infected pregnant women toward the COVID-19 outbreak in order to constitute base data for detailed counseling and to develop targeted messages.Patients and methods: This cross-sectional survey research presented analysis of prospectively collected data yielded at a single tertiary \"Coronavirus Pandemic Hospital\" referral center for a ten days period following the first confirmed death due to the COVID-19 pandemic in Turkey. Non-infected women with a confirmed pregnancy over 30th gestational week were consecutively included. A patient-reported non-validated questionnaire formed by the expert committee that includes 15 specific questions was used. Non-infected, pregnant women over 30th gestational week who applied to the outpatient clinic were consecutively included. A total of 213 women were enrolled, 37 were excluded: 7 for being in the first trimester, 3 were illiterate, and 27 were Syrian refugees having difficulties in translation.Results: A total of 172 pregnant women were included. Overall, four women refused to participate to the survey (1.9%). The mean age was 27.5 \u00b1 5.3 years. Median gestational week and parity were 35 \u00b1 11 weeks and 1 \u00b1 2, respectively. Pregnant women were observed to trust the authorities (65%) and the healthcare staff (92.4%), and their respect was increased (82.5%) during the outbreak. Majority of the women (87.2%) comply with the self-quarantine rules. Half of the women (52%) reported that they felt vulnerable and predominantly were concerned (80%). Approximately one-third of the women constantly keep thinking that they may get infected (35.5%) or they might get infected during/following the delivery or their baby might get infected after being born (42%). Half of the women (50%) were reported that they either had no idea about or think the breastfeeding is not safe during the outbreak. About 45% of the women were confused or had doubts about if the mode of delivery may be affected by the pandemic. Greater part of the participants does not know if COVID-19 might cause birth defects (76%) or preterm birth (64.5%). Counseling flow keys helping pregnant women to overcome misleads, regarding the COVID-19 outbreak is proposed.Conclusions: Non-infected pregnant women with a viable pregnancy at near term were observed to have positive attitude and compliance toward the COVID-19 outbreak and frontline healthcare staff; increased concern and vulnerability; and restricted knowledge about the pregnancy-related outcomes. While the clinical evidence was growing rapidly, this data may guide obstetricians and midwives to perceive what accurate information should be provided to the pregnant women.", "qid": 27, "docid": "kf7a9ccd", "rank": 99, "score": 7.58289909362793}, {"content": "Title: Predicting COVID-19 spread and public health needs to contain the pandemic in West-Africa Content: The novel coronavirus (COVID-19) pandemic is causing devastating demographic, social, and economic damage globally. Understanding current patterns of the pandemic spread and forecasting its long-term trajectory is essential in guiding policies aimed at curtailing the pandemic. This is particularly important in regions with weak economies and fragile health care systems such as West-Africa. We formulate and use a deterministic compartmental model to (i) assess the current patterns of COVID-19 spread in West-Africa, (ii) evaluate the impact of currently implemented control measures, and (iii) predict the future course of the pandemic with and without currently implemented and additional control measures in West-Africa. An analytical expression for the threshold level of control measures (involving a reduction in the effective contact rate) required to eliminate the pandemic is computed. Considering currently applied health control measures, numerical simulations of the model using baseline parameter values estimated from West-African COVID-19 data project a 60% reduction in the daily number of cases when the epidemic attains its peak. More reduction in the number of cases will be achieved if additional public health control measures that result in a reduction in the effective contact rate are implemented. We found out that disease elimination is difficult when more asymptomatic individuals contribute in transmission or are not identified and isolated in a timely manner. However, maintaining a baseline level of asymptomatic isolation and a low transmission rate will lead to a significant reduction in the number of daily cases when the pandemic peaks. For example, at the baseline level of asymptomatic isolation, at least a 53% reduction in the transmission rate is required for disease elimination, while disease elimination is also possible if asymptomatic individuals are identified and isolated within 2 days (after the incubation period). Combining two or more measures is better for disease control, e.g., if asymptomatic humans are contact traced or identified and isolated in less than 3 days then only about a 31% reduction in the disease transmission rate is required for disease elimination. Furthermore, we showed that the currently implemented measures caused the time-dependent effective reproduction number to reduce by approximately 37% from February 28, to August 24, 2020. We conclude that COVID-19 elimination requires more control measures than what is currently being applied inWest-Africa and that mass testing and contact tracing in order to identify and isolate asymptomatic individuals early is very important in curtailing the burden of the pandemic.", "qid": 27, "docid": "iil8bzrm", "rank": 100, "score": 7.579599857330322}]}
{"query": "what evidence is there for the value of hydroxychloroquine in treating Covid-19?", "hits": [{"content": "Title: Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin for COVID-19: what is the evidence and what are the risks? Content: The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.", "qid": 28, "docid": "wnb4cltt", "rank": 1, "score": 11.387100219726562}, {"content": "Title: Hydroxychloroquine as prophylaxis or treatment for COVID-19: What does the evidence say? Content: Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.", "qid": 28, "docid": "9eo0leey", "rank": 2, "score": 11.153599739074707}, {"content": "Title: QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review Content: Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.", "qid": 28, "docid": "e1otbzt3", "rank": 3, "score": 10.9197998046875}, {"content": "Title: QT prolongation, torsades de pointes and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review Content: Chloroquine and hydroxychloroquine are now being widely used as treatments for COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk of torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched in MEDLINE and Embase, as well as grey literature up to April 17, 2020, on the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This resulted in 390 unique records, of which fourteen were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in two COVID-19 patients out of a group of 28 treated with high-dose chloroquine. A limitation of these results is unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT interval prolongation and potentially increase the risk of arrhythmia. Daily ECG monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.", "qid": 28, "docid": "sm0112e3", "rank": 4, "score": 10.919798851013184}, {"content": "Title: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19 Content: Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it\u2019s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government\u2019s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians\u2019 attitudes? Finally, what are the government, physicians, and patient\u2019s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government\u2019s, practitioner\u2019s and patient\u2019s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.", "qid": 28, "docid": "rffp6qe2", "rank": 5, "score": 10.345399856567383}, {"content": "Title: Potential therapeutic agents against COVID-19: What we know so far Content: The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.", "qid": 28, "docid": "eitnkdi9", "rank": 6, "score": 9.86870002746582}, {"content": "Title: Former FDA leaders decry emergency authorization of malaria drugs for coronavirus Content: The recent Food and Drug Administration (FDA) emergency use authorization (EUA) for two malaria drugs to treat COVID-19, based on thin evidence of efficacy, has jeopardized research to learn the drugs\u2019 real value against the pandemic coronavirus, say former agency executives under President Donald Trump and former President Barack Obama They also charge that the 28 March EUA for chloroquine phosphate and hydroxychloroquine sulfate undermines FDA\u2019s scientific authority because it appeared to be a response not to scientific evidence, but to fervent advocacy of the drugs by Trump and other political figures FDA has multiple mechanisms to allow the use of unapproved, experimental drugs for small numbers of desperately ill patients outside of clinical trials Because chloroquine and hydroxychloroquine are approved for malaria, doctors could prescribe them \u201coff label\u201d for COVID-19 patients even without the EUA Since Trump first endorsed the drugs on 19 March, however, shortages have been reported, depriving some people with autoimmune disorders such as lupus who also depend on hydroxychloroquine The EUA will immediately add tens of millions of doses of the drugs for distribution to hospitalized COVID-19 patients through health care centers", "qid": 28, "docid": "bnq02x8q", "rank": 7, "score": 9.868399620056152}, {"content": "Title: Should azithromycin be used to treat COVID-19? A rapid review Content: BACKGROUND: There are no established effective treatments for COVID-19. While novel drugs are being developed, azithromycin has been identified as a candidate treatment in the interim. AIM: To review the evidence for the effectiveness and safety of azithromycin in treating COVID-19. DESIGN & SETTING: A rapid review of the literature was conducted. METHOD: Electronic searches were conducted on 16 April 2020 of PubMed, TRIP, EPPI COVID Living Map, MedRxiv, GoogleScholar, and Google. In vivo and in vitro studies were included assessing the safety and effectiveness of azithromycin for treatment of COVID-19, and/or the activity of azithromycin against SARS-CoV-2. In vivo studies needed to include a comparator group. RESULTS: Three studies were identified, two in vitro and one in vivo, which were suitable for inclusion. All three were published as pre-prints. The in vitro studies revealed conflicting results, with one finding anti-SARS-CoV-2 activity for azithromycin alone, while the other found activity against SARS-CoV-2 only when azithromycin was combined with hydroxychloroquine. A small trial of 36 patients, with high risk of bias, found superior viral clearance in patients with COVID-19 treated with azithromycin and hydroxychloroquine combined, compared with hydroxychloroquine alone. CONCLUSION: There is no evidence to support the use of azithromycin for the treatment of COVID-19 outside of the context of clinical trials, unless it is used to treat bacterial super-infection. There is extremely limited evidence of a possible synergy between azithromycin and hydroxychloroquine. The adverse events profile of azithromycin in the context of COVID-19 has not yet been established. Well-conducted clinical trials are urgently needed in this area.", "qid": 28, "docid": "1n6d1gco", "rank": 8, "score": 9.573200225830078}, {"content": "Title: Macrolides and viral infections: focus on azithromycin in COVID-19 pathology Content: The emergence of the new COVID-19 virus is proving to be a challenge in seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appears to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin in reducing production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress, and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against Middle East Respiratory syndrome (MERS). Some preliminary evidence has demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. First, a French trial demonstrated 100% virological negativizing of six patients treated with azithromycin plus hydroxychloroquine vs. 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (P < 0.05). On the other hand, another case series revealed no efficacy at all on 11 patients treated with the same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of potential QT prolongation. In fact, both drugs have this as a potential side effect and evidence regarding the safe use of this combination is controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidence and some preliminary results in COVID-19, azithromycin could have potential in the fight against this new disease.", "qid": 28, "docid": "79fury6c", "rank": 9, "score": 9.504899978637695}, {"content": "Title: Macrolides and viral infections: focus on azithromycin in COVID-19 pathology Content: The emergence of the new disease COVID-19, is posing the challenge of seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appeared to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin to reduce production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against MERS. Some preliminary evidences have demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. Firstly, a French trial demonstrated 100% of virological negativization of six patients treated with azithromycin plus hydroxychloroquine vs 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (p<0.05). On the other hand, another case series revealed no efficacy at all on eleven patients treated with same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of the potential Qt prolongation. In fact, both drugs have this as potential side effect and evidences regarding the safety use of this combination are controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidences and some preliminary results in COVID-19, azithromycin could have a potential in the fight against this new disease.", "qid": 28, "docid": "k50qvr4w", "rank": 10, "score": 9.504899024963379}, {"content": "Title: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.", "qid": 28, "docid": "safr9z37", "rank": 11, "score": 9.466500282287598}, {"content": "Title: Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review Content: Background: Coronavirus pandemic is currently a global public health emergency. At present, no pharmacological treatment is known to treat this condition, and there is a need to review the available treatments. Objective: While there have been studies to describe the role of chloroquine and hydroxychloroquine in various viral conditions, there is limited information about the use of them in COVID-19. This systematic review aims to summarize the available evidence regarding the role of chloroquine in treating coronavirus infection. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search was performed using PUBMED & Google Scholar to find articles about the role of CQ in COVID-19 patients. Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review. All the articles mentioned about the role of chloroquine and /or hydroxychloroquine in limiting the infection with SARS-CoV-2 (the virus causing COVID-19). Conclusions: There is theoretical, experimental, preclinical and clinical evidence of the effectiveness of chloroquine in patients affected with COVID-19. There is adequate evidence of drug safety from the long-time clinical use of chloroquine and hydroxychloroquine in other indications. More data from ongoing and future trials will add more insight into the role of chloroquine and hydroxychloroquine in COVID-19 infection.", "qid": 28, "docid": "0lk8eujq", "rank": 12, "score": 9.425100326538086}, {"content": "Title: Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19) Content: Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "qid": 28, "docid": "n3cg3w9v", "rank": 13, "score": 9.407600402832031}, {"content": "Title: Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19). Content: Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "qid": 28, "docid": "px2o98cv", "rank": 14, "score": 9.407599449157715}, {"content": "Title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Content: The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.", "qid": 28, "docid": "l6l24pco", "rank": 15, "score": 9.131600379943848}, {"content": "Title: Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients Content: Background: COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and means of prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulfate may be efficacious against COVID-19, our hospitals began using zinc sulfate as add-on therapy to hydroxychloroquine and azithromycin. We performed a retrospective observational study to compare hospital outcomes among patients who received hydroxychloroquine and azithromycin plus zinc versus hydroxychloroquine and azithromycin alone. Methods: Data was collected from electronic medical records for all patients being treated with admission dates ranging from March 2, 2020 through April 5, 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. Patients in the study were excluded if they were treated with other investigational medications. Results: The addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration. In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744). Conclusion: This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.", "qid": 28, "docid": "4pcv1i3i", "rank": 16, "score": 9.079400062561035}, {"content": "Title: [Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection]. Content: The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "qid": 28, "docid": "hjl6vdwy", "rank": 17, "score": 9.070300102233887}, {"content": "Title: [Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection] Content: The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "qid": 28, "docid": "v5qhqn9o", "rank": 18, "score": 9.07029914855957}, {"content": "Title: Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine Content: SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans.", "qid": 28, "docid": "aexlwq79", "rank": 19, "score": 8.987299919128418}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID\u201019 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID\u201019). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID\u201019 are treated with these agents and more evidence accumulates, there continues to be no high\u2010quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto\u2010immune conditions, and provided a component in the original rationale for their use in patients with COVID\u201019, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID\u201019. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID\u201019, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID\u201019 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case\u2010by\u2010case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 28, "docid": "75vvix5o", "rank": 20, "score": 8.874699592590332}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID-19 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 28, "docid": "87uhx3pt", "rank": 21, "score": 8.874698638916016}, {"content": "Title: Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study Content: The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.", "qid": 28, "docid": "t1vom8f3", "rank": 22, "score": 8.830599784851074}, {"content": "Title: Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID-19 patients Content: Translation of in vitro antiviral activity to the in vivo setting is crucial to identify potentially effective dosing regimens of hydroxychloroquine. In vitro EC50/EC90 values for hydroxychloroquine should be compared to the in vivo free extracellular tissue concentration, which is similar to the free plasma hydroxychloroquine concentration.", "qid": 28, "docid": "rd766a4w", "rank": 23, "score": 8.800600051879883}, {"content": "Title: Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19. Content: OBJECTIVE The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on \"COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.", "qid": 28, "docid": "fgxbyb7l", "rank": 24, "score": 8.749199867248535}, {"content": "Title: Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19 Content: OBJECTIVE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS: We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on \"COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS: For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS: Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.", "qid": 28, "docid": "hf5b7gxf", "rank": 25, "score": 8.749198913574219}, {"content": "Title: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 Content: BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).", "qid": 28, "docid": "1na13h2u", "rank": 26, "score": 8.697500228881836}, {"content": "Title: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 Content: BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)", "qid": 28, "docid": "pzqmg22v", "rank": 27, "score": 8.69749927520752}, {"content": "Title: Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin Content: BACKGROUND: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. METHODS: We performed 12\u2011lead ECGs and 12\u2011lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. RESULTS: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc \u2265 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had \u22651 run of non-sustained ventricular tachycardia (p = .4). No patients showed \u201cR on T\" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. CONCLUSION: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.", "qid": 28, "docid": "ibhftsn5", "rank": 28, "score": 8.635700225830078}, {"content": "Title: Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin Content: BACKGROUND: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. METHODS: We performed 12\u00adlead ECGs and 12\u00adlead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. RESULTS: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc &#8805; 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had &#8805;1 run of non-sustained ventricular tachycardia (p = .4). No patients showed \"R on T\" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. CONCLUSION: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.", "qid": 28, "docid": "o6kx1264", "rank": 29, "score": 8.635699272155762}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Content: BACKGROUND Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.", "qid": 28, "docid": "fanupn22", "rank": 30, "score": 8.605199813842773}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review Content: BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 28, "docid": "fs8r5ze0", "rank": 31, "score": 8.605198860168457}, {"content": "Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "qid": 28, "docid": "b6aeu1ph", "rank": 32, "score": 8.576199531555176}, {"content": "Title: Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020) Content: Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 250,000 confirmed cases as of March 21, 2020. An open-label clinical trial has just concluded, suggesting improved resolution of viremia with use of two existing therapies: hydroxychloroquine (HCQ) as monotherapy, and in combination with azithromycin (HCQ-AZ). The results of this important trial have major implications for global policy in the rapid scale-up and response to this pandemic. The authors present results with p-values for differences in proportions between the study arms, but their analysis is not able to provide effect size estimates. To address this gap, more modern analytical methods including survival models, have been applied to these data, and show modest to no impact of HCQ treatment, with more significant effects from the HCQ-AZ combination, potentially suggesting a role for co-infections in COVID-19 pathogenesis. The trial of Gautret and colleagues, with consideration of the effect sizes, and p-values from multiple models, does not provide sufficient evidence to support wide-scale rollout of HCQ monotherapy for the treatment of COVID-19; larger randomized studies should be considered. The trial of Gautret and colleagues, with consideration of the effect sizes, and p-values from multiple models, does not provide sufficient evidence to support wide-scale rollout of HCQ monotherapy for the treatment of COVID-19; larger randomized studies should be considered. These data also suggest further randomized-controlled studies of HCQ-AZ combination therapy should be undertaken.", "qid": 28, "docid": "azvbl4ie", "rank": 33, "score": 8.575900077819824}, {"content": "Title: Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review Content: BACKGROUND: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. AIM: To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. DESIGN & SETTING: A rapid review of the literature was conducted. METHOD: Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. RESULTS: There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. CONCLUSION: At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.", "qid": 28, "docid": "86h5ptxm", "rank": 34, "score": 8.53499984741211}, {"content": "Title: Emerging Treatment and Prevention Strategies against COVID-19: A Brief Update Content: Patients with novel coronavirus disease 2019 (COVID-19) are at significantly increased risk for mortality and morbidity. Current management remains supportive care, ranging from symptomatic outpatient management to full\u2013intensive care support, including intravenous fluids, invasive, and non-invasive oxygen supplementation. In patients with septic shock, treatment with antibiotics and vasopressors are recommended to keep mean arterial pressure (MAP) \u2265 65 mm Hg and lactate < 2 mmol/L. Because of the lack of effectiveness and possible adverse effects, routine corticosteroids should be avoided unless they are indicated for another reason (exacerbation of asthma or chronic obstructive pulmonary disease [COPD], and septic shock in whom fluids and vasopressors do not restore hemodynamic stability). There is currently no sufficient evidence of efficacy of hydroxychloroquine/chloroquine, remdesivir, and other antivirals in the treatment or prevention of COVID-19. Limited evidence shows that COVID-19 convalescent plasma can be used as a treatment of COVID-19 without the occurrence of severe adverse events. Drug regulatory agencies granted an emergency-use authorization of chloroquine/hydroxychloroquine and remdesivir to treat patients when a clinical trial is not available or participation is not feasible. Chloroquine and hydroxychloroquine are associated with QT interval prolongation and life-threatening cardiac arrhythmia in patients with pre-existing cardiovascular disease. Guidelines are issued for use of convalescent plasma in patients with serious or immediately life-threatening COVID-19. Data from several ongoing randomized controlled trials will provide further evidence regarding the safety and efficacy of these drugs for the treatment of COVID-19.", "qid": 28, "docid": "6bdzut3d", "rank": 35, "score": 8.48009967803955}, {"content": "Title: Chloroquine, hydroxychloroquine, and COVID-19: systematic review and narrative synthesis of efficacy and safety Content: Background: The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the repurposing of existing drugs. Several drugs are now being repurposed with the aim of identifying if these drugs provide some level of disease resolution. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ), first developed as an antimalarial therapy. There is increasing concern with regards to the efficacy and safety of these agents. The aims of this review are to systematically identify and collate studies describing the use of CQ and HCQ in human clinical trials and provide a detailed synthesis of evidence of its efficacy and safety. Methods and Findings: Searches for (COVID AND chloroquine [title/abstract] AND outcomes[full text]) and two (COVID AND hydroxychloroquine[title/abstract] AND outcomes[full text]) yielded 272 unique articles. Unique articles were manually checked for inclusion and exclusion criteria and also subjected to a quality appraisal assessment. A total of 19 articles were included in the systematic review. Seventy-five percent of observational studies employing an endpoint specific to efficacy recorded no significant difference in the attainment of outcomes, between COVID-19 patients given a range of CQ and/or HCQ doses, and the control groups. All clinical trials and 82% of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Seventy-five percent of the total papers focusing on cardiac side-effects found a greater incidence among patients administered a wide range of CQ and/or HCQ doses, with QTc prolongation the most common finding, in addition to its consequences of VT and cardiac arrest. Of the total studies using mortality rate as an end-point, 60% reported no significant change in the risk of death, while 30% showed an elevation, and 10% a depression, in treated relative to control patients. Conclusion: The strongest available evidence suggests that, relative to standard in-hospital management of symptoms, the use of CQ and HCQ to treat hospitalised COVID-19 patients has likely been unsafe. At the very least, the poor quality of data failing to find any significant changes in the risk of VT should preclude definitive judgment on drug safety until the completion of high-quality randomised clinical trials.", "qid": 28, "docid": "srr2n28u", "rank": 36, "score": 8.461899757385254}, {"content": "Title: Commentary on \u201cHydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial\u201d by Gautret et al Content: The results of a clinical trial comparing hydroxychloroquine with or without azithromycin to the standard of care for the treatment of COVID-19 were recently published by Philippe Gautret et al. This study provides outstanding results for the combination of hydroxychloroquine and azithromycin over the standard of care, but the evidence was deemed insufficiently robust to warrant a public health decision to widen the use of hydroxychloroquine for the treatment of COVID-19. We provide a scientific critical review of the Gautret et al. publication, put the results in the context of the current knowledge, provide an evaluation of the validity of the results (from a methodologic perspective), and discuss public health implications. The study has a number of limitations, including small sample size, lack of comparability between patients in active treatment and control arms, lack of blinding, use of interim analyses without controlling for the risk of type 1 error, use of analysis in the per-protocol population instead of the intention-to-treat population, and inconsistencies between the study protocol and article. However, none of these observations is of a nature to reverse the conclusions. The study brings useful knowledge consistent with available evidence and clinical practice from China and South Korea, which could have prompted quicker policy decision-making.", "qid": 28, "docid": "gg706q8s", "rank": 37, "score": 8.461898803710938}, {"content": "Title: Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review Content: In a search to find effective treatments for COVID-19, chloroquine and hydroxychloroquine have gained attention. We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.", "qid": 28, "docid": "w1au4pyl", "rank": 38, "score": 8.461897850036621}, {"content": "Title: Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019 Content: Background/Aims: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. Methods: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. Results: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. Conclusions: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.", "qid": 28, "docid": "lvc78cue", "rank": 39, "score": 8.40530014038086}, {"content": "Title: Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019. Content: Background/Aims The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. Methods This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. Results Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. Conclusions Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.", "qid": 28, "docid": "qoinntar", "rank": 40, "score": 8.405299186706543}, {"content": "Title: Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review Content: Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. Graphical Abstract.", "qid": 28, "docid": "wuv1kafa", "rank": 41, "score": 8.390700340270996}, {"content": "Title: Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring. Content: Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine, or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett's) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc \u2265500 ms (if QRS <120 ms) or QTc \u2265550 ms (if QRS \u2265120 ms) and b) increased QTc of \u226560 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62\u00b117 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448\u00b129 ms and increased to 459\u00b136 ms (p=0.005) with medications. Significant prolongation was observed only in men (18\u00b143 ms vs -0.2\u00b128 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared to either drug, with much greater prolongation with combination vs. azithromycin (17\u00b139 vs. 0.5\u00b140 ms, p=0.07). No patients manifested torsades de pointes. Conclusions Overall 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.", "qid": 28, "docid": "jtpmw9kb", "rank": 42, "score": 8.322600364685059}, {"content": "Title: Serious Adverse Events Associated With Hydroxychloroquine Amidst COVID-19 Pandemic: Case Series and Literature Review Content: COVID-19 represents a global health crisis. Several studies are evaluating potential therapies including hydroxychloroquine (HCQ) which is given to patients based on limited observational evidence. However, it can cause serious adverse events. Moreover, recent studies showed no benefits due to HCQ. We present two COVID-19 patients treated with HCQ and had adverse events.", "qid": 28, "docid": "q1akwoo1", "rank": 43, "score": 8.305500030517578}, {"content": "Title: Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review Content: Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I(2) test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using \u2018Review manager software version 5.3\u2019. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I(2) = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I(2) = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I(2) = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11481-020-09930-x) contains supplementary material, which is available to authorized users.", "qid": 28, "docid": "uljaj8gd", "rank": 44, "score": 8.298299789428711}, {"content": "Title: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 Content: BACKGROUND: Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the U.S. Food and Drug Administration has authorized the emergency use of this drug when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence. METHODS: We performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We determined the association between treatment and the primary outcomes using competing risk hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death were taken into account as competing risks and subdistribution hazard ratios are presented. RESULTS: A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group. CONCLUSIONS: In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.", "qid": 28, "docid": "zoipx650", "rank": 45, "score": 8.274200439453125}, {"content": "Title: Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring Content: Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc &#8805;500 ms (if QRS <120 ms) or QTc &#8805;550 ms (if QRS &#8805;120 ms) and (2) QTc increase of &#8805;60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62\u00b117 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448\u00b129 ms and increased to 459\u00b136 ms (P=0.005) with medications. Significant prolongation was observed only in men (18\u00b143 ms versus -0.2\u00b128 ms in women; P=0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17\u00b139 ms versus 0.5\u00b140 ms; P=0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.", "qid": 28, "docid": "emb5bl9f", "rank": 46, "score": 8.170299530029297}, {"content": "Title: Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring Content: Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc [\u2265]500 ms (if QRS <120 ms) or QTc [\u2265]550 (if QRS [\u2265]120 ms) and b) increased QTc of [\u2265]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62{+/-}17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. In a multivariable logistic regression, age, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.", "qid": 28, "docid": "6qz40fnv", "rank": 47, "score": 8.136500358581543}, {"content": "Title: Intentional Hydroxychloroquine Overdose Treated with High-Dose Diazepam: an Increasing Concern in the COVID-19 Pandemic Content: INTRODUCTION: Recent attention on the possible use of hydroxychloroquine and chloroquine to treat COVID-19 disease has potentially triggered a number of overdoses from hydroxychloroquine. Toxicity from hydroxychloroquine manifests with cardiac conduction abnormalities, seizure activity, and muscle weakness. Recognizing this toxidrome and unique management of this toxicity is important in the COVID-19 pandemic. CASE REPORT: A 27-year-old man with a history of rheumatoid arthritis presented to the emergency department 7 hours after an intentional overdose of hydroxychloroquine. Initial presentation demonstrated proximal muscle weakness. The patient was found to have a QRS complex of 134 ms and QTc of 710 ms. He was treated with early orotracheal intubation and intravenous diazepam boluses. Due to difficulties formulating continuous diazepam infusions, we opted to utilize an intermitted intravenous bolus strategy that achieved similar effects that a continuous infusion would. The patient recovered without residual side effects. DISCUSSION: Hydroxychloroquine toxicity is rare but projected to increase in frequency given its selection as a potential modality to treat COVID-19 disease. It is important for clinicians to recognize the unique effects of hydroxychloroquine poisoning and initiate appropriate emergency maneuvers to improve the outcomes in these patients.", "qid": 28, "docid": "lv3up9d9", "rank": 48, "score": 8.118499755859375}, {"content": "Title: Model informed dosing of Hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and Gaps Content: AIMS: In the absence of a commonly agreed dosing protocol based on pharmacokinetic considerations, the dose and treatment duration for hydroxychloroquine (HCQ) COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS: We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS: Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800mg day on D1 followed by 600mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION: Our results were clear indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best the benefit/risk balance.", "qid": 28, "docid": "ddqxzcnt", "rank": 49, "score": 8.102499961853027}, {"content": "Title: Model informed dosing of Hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and Gaps. Content: AIMS In the absence of a commonly agreed dosing protocol based on pharmacokinetic considerations, the dose and treatment duration for hydroxychloroquine (HCQ) COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800mg day on D1 followed by 600mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION Our results were clear indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best the benefit/risk balance.", "qid": 28, "docid": "nnoswa5j", "rank": 50, "score": 8.102499008178711}, {"content": "Title: Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence Content: Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "qid": 28, "docid": "5jafu8tw", "rank": 51, "score": 8.025500297546387}, {"content": "Title: Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence. Content: Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "qid": 28, "docid": "an28gfe4", "rank": 52, "score": 8.02549934387207}, {"content": "Title: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients Content: Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. Design: Systematic review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study Selection: Published and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome Measures: The outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: 49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). Conclusion: Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review Registration: PROSPERO 2020: CRD42020186527.", "qid": 28, "docid": "9hdft1tc", "rank": 53, "score": 8.018099784851074}, {"content": "Title: Practice considerations on the use of investigational anti\u2010COVID\u201019 medications: Dosage, administration and monitoring Content: WHAT IS KNOWN AND OBJECTIVE: Understanding investigational medications is important. Many older drugs are being investigated for repurposing against COVID\u201019. We comment on various drugs currently undergoing such trials to optimize their safe use. COMMENT: We describe medications used during early COVID\u201019 outbreaks in South Korea, focusing on practice aspects including the method of drug administration, drug formulation, patient\u2010monitoring for adverse reactions and drug interactions informed by our experience during the 2015 outbreak of Middle East respiratory syndrome (MERS). We comment on hydroxychloroquine, chloroquine, lopinavir/ritonavir with zinc supplement, remdesivir, tocilizumab, ciclesonide, niclosamide and high\u2010dose intravenous immunoglobulin (IVIG). WHAT IS NEW AND CONCLUSION: Effective therapies are urgently needed to manage COVID\u201019, and existing drugs such as antivirals and antimalarials are under investigation for repurposing to meet this need. This process requires up\u2010to\u2010date drug information to ensure optimum use, particularly safety and efficacy profiles of the medications, until convincing evidence is reported.", "qid": 28, "docid": "4wly1s1p", "rank": 54, "score": 8.00160026550293}, {"content": "Title: Practice considerations on the use of investigational anti-COVID-19 medications: Dosage, administration and monitoring Content: WHAT IS KNOWN AND OBJECTIVE: Understanding investigational medications is important. Many older drugs are being investigated for repurposing against COVID-19. We comment on various drugs currently undergoing such trials to optimize their safe use. COMMENT: We describe medications used during early COVID-19 outbreaks in South Korea, focusing on practice aspects including the method of drug administration, drug formulation, patient-monitoring for adverse reactions and drug interactions informed by our experience during the 2015 outbreak of Middle East respiratory syndrome (MERS). We comment on hydroxychloroquine, chloroquine, lopinavir/ritonavir with zinc supplement, remdesivir, tocilizumab, ciclesonide, niclosamide and high-dose intravenous immunoglobulin (IVIG). WHAT IS NEW AND CONCLUSION: Effective therapies are urgently needed to manage COVID-19, and existing drugs such as antivirals and antimalarials are under investigation for repurposing to meet this need. This process requires up-to-date drug information to ensure optimum use, particularly safety and efficacy profiles of the medications, until convincing evidence is reported.", "qid": 28, "docid": "7v4v7owe", "rank": 55, "score": 8.001599311828613}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 28, "docid": "98zpr960", "rank": 56, "score": 7.927199840545654}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution. Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 28, "docid": "opbozg55", "rank": 57, "score": 7.927198886871338}, {"content": "Title: Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review Content: BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of [\u2265] 500 ms or an increase of [\u2265] 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.", "qid": 28, "docid": "2txzi7kb", "rank": 58, "score": 7.908699989318848}, {"content": "Title: Hydroxychloroquine and mortality risk of patients with COVID-19: a systematic review and meta-analysis of human comparative studies Content: Background: Global COVID-19 deaths reached at least 400,000 fatalities. Hydroxychloroquine is an antimalarial drug that elicit immunomodulatory effects and had shown in vitro antiviral effects against SRAS-CoV-2. This drug divided opinion worldwide in the medical community but also in the press, the general public and in public health policies. The aim of this systematic review and this meta-analysis was to bring a new overview on this controversial drug and to assess whether hydroxychloroquine could reduce COVID-19 mortality risk in hospitalized patients. Methods and Findings: Pubmed, Web of Science, Cochrane Library, MedRxiv and grey literature were searched until 10 June 2020. Only studies of COVID-19 patients treated with hydroxychloroquine (with or without azithromycin) compared with a comparative standard care group and with full-text articles in English were included. Studies reporting effect sizes as Odds Ratios, Hazard Ratio and Relative Risk for mortality risk and the number of deaths per groups were included. This meta-analysis was conducted following PRISMA guidelines and registered on PROSPERO (Registration number: CRD42020190801). Independent extraction has been performed by two independent reviewers. Effect sizes were pooled using a random-effects model. The initial search leaded to 112 articles, from which 16 articles met our inclusion criteria. 15 studies were retained for association between hydroxychloroquine and COVID-19 survival including 15,081 patients (8,072 patients in the hydroxychloroquine arm and 7,009 patients in the standard care arm with respectively, 1,578 deaths and 1,423 deaths). 6 studies were retained for hydroxychloroquine with azithromycin. Hydroxychloroquine was not significantly associated with mortality risk (pooled Relative Risk RR=0.82 (95% Confidence Interval: 0.62-1.07, I2=82, Pheterogeneity<0.01, n=15)) within hospitalized patients, nor in association with azithromycin (pooled Relative Risk RR=1.33 (95% CI: 0.92-1.92, I2=75%, Pheterogeneity<0.01, n=6)), nor in the numerous subgroup analysis by study design, median age population, published studies (vs unpublished articles), level of bias risk. However, stratified analysis by continents, we found a significant decreased risk of mortality associated with hydroxychlroquine alone but not with azithromycin among European (RR= 0.62 (95%CI: 0.41-0.93, n=7)) and Asian studies (RR=0.36 (95%CI:0.18-0.73, n=1)), with heterogeneity detected across continent (Pheterogeneity between=0.003). These finding should be interpreted with caution since several included studies had a low quality of evidence with a small sample size, a lack of adjustment on potential confounders or selection and intervention biases. Conclusion: Our meta-analysis does not support the use of hydroxychloroquine with or without azithromycin to reduce COVID-19 mortality in hospitalized patients. It raises the question of the hydroxychloroquine use outside of clinical trial. Additional results from larger randomised controlled trials are needed", "qid": 28, "docid": "tsmqssjm", "rank": 59, "score": 7.8744001388549805}, {"content": "Title: Chloroquine, hydroxychloroquine and COVID-19 Content: The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1\u20132 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.", "qid": 28, "docid": "igrmfj0j", "rank": 60, "score": 7.859799861907959}, {"content": "Title: Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network Content: On March 28, 2020, in response to the rapidly accelerating COVID-19 pandemic, U.S FDA issued emergency use authorization for hydroxychloroquine (HCQ) in hospitalized COVID-19 patients based on limited in-vitro and anecdotal clinical data. Analysis of the accumulated real-world data utilizing electronic medical records (EMR) could indicate HCQ therapy benefits as we await the results of clinical trials. However, any such analysis of retrospective observational data should account for variables such as demographics and comorbidities that could affect treatment strategies or outcomes. Therefore, we report the outcomes of HCQ treatment in a propensity-matched cohort of COVID-19 hospitalized patients. Our analysis of a large retrospective cohort of hospitalized COVID-19 patients treated with HCQ did not show benefits in mortality or the need for mechanical ventilation when compared to a matched cohort of patients who did not receive HCQ.", "qid": 28, "docid": "ax4aw25i", "rank": 61, "score": 7.852499961853027}, {"content": "Title: Hydroxychloroquine treatment in COVID\u201019: a descriptive observational analysis of 30 cases from a single center in Wuhan, China Content: Hydroxychloroquine (HCQ) garnered scientific attention in early February following publication of reports showing in vitro activity of chloroquine (CQ) against COVID\u201019. While studies are mixed on this topic, the therapeutic effect of HCQ or CQ still need more valid clinical evidence. In this descriptive observational study, we aimed to discuss the treatment response of HCQ in COVID\u201019 infected patients and 30 cases were included. The demographic, treatment, laboratory parameters of C\u2010reactive protein (CRP) and interleukin\u20106 (IL\u20106) before and after HCQ therapy and clinical outcome in the 30 COVID\u201019 patients were assessed. In order to evaluate the effect of mediation time point, we also divided these cases into two groups, patients began administrated with HCQ within 7 days hospital (defined as early delivery group) and 7 days after hospital (defined as later delivery group). We found that, the elevated IL\u20106, a risk factor in severe patients were reduced to normal level after HCQ treatment. More importantly, patients treated with HCQ at the time of early hospital recovered faster than those who treated later or taken as second line choose for their obvious shorter hospitalization time. In summary, early use of HCQ was better than later use and the effect of IL\u20106 and CRP level can not be ruled out. This article is protected by copyright. All rights reserved.", "qid": 28, "docid": "hd5yvs5x", "rank": 62, "score": 7.84250020980835}, {"content": "Title: Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID-19 Pandemic Content: OBJECTIVE: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID-19. We set out to understand how the COVID-19 pandemic has impacted the lives of these patients in the United States. METHODS: Participants in a US-wide longitudinal observational registry responded to a supplemental COVID-19 questionnaire by e-mail on March 25, 2020, about their symptoms, COVID-19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free-text comment fields. RESULTS: Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID-19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID-19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. CONCLUSION: After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID-19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.", "qid": 28, "docid": "bto6hssq", "rank": 63, "score": 7.813700199127197}, {"content": "Title: Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID\u201019 Pandemic Content: OBJECTIVE: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID\u201019. We set out to understand how the COVID\u201019 pandemic has impacted the lives of these patients in the United States. METHODS: Participants in a US\u2010wide longitudinal observational registry responded to a supplemental COVID\u201019 questionnaire by e\u2010mail on March 25, 2020, about their symptoms, COVID\u201019 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free\u2010text comment fields. RESULTS: Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID\u201019 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID\u201019 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. CONCLUSION: After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID\u201019 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.", "qid": 28, "docid": "s623p0n6", "rank": 64, "score": 7.813699245452881}, {"content": "Title: Antiretroviral HIV drugs in COVID-19 research: promises and risks. An opinion piece Content: The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarise the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.", "qid": 28, "docid": "2vik7mwl", "rank": 65, "score": 7.729700088500977}, {"content": "Title: Antiretroviral HIV drugs in COVID\u201019 research: promises and risks. An opinion piece Content: The unprecedented global scale of COVID\u201019 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarise the evidence for antiretrovirals to treat COVID\u201019 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.", "qid": 28, "docid": "9kuhu76i", "rank": 66, "score": 7.72969913482666}, {"content": "Title: Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of COVID-19: Psychopharmacological Interactions and Neuropsychiatric Sequelae Content: BACKGROUND: Chloroquine and hydroxychloroquine are among several experimental treatments being investigated in the urgent response to the COVID-19. With increased use of these medications, physicians need to become knowledgeable of these drugs\u2019 neuropsychiatric side effects and interactions with psychiatric medications. METHODS: Literature review was performed in PubMed from 1950-2020 regarding psychiatric topics and targeted pharmacological properties of chloroquine and hydroxychloroquine. REVIEW: First, chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications, and psychiatric medications that interfere with CYP2D6 or CYP3A4 activity could alter chloroquine and hydroxychloroquine levels. Second, they may prolong the QT interval, warranting caution with concomitant prescription of other QT prolonging agents. Finally, neuropsychiatric side effects are very uncommon but possible, and include a potentially prolonged phenomenon of \u201cpsychosis following chloroquine.\u201d Hydroxychloroquine has less information available about its neuropsychiatric side effects than chloroquine, with psychosis literature limited to several case reports. It is not clear whether patients with psychiatric illness are more vulnerable to neuropsychiatric sequela of these medications, however, overdose on these medications by suicidal patients has high risk of mortality. CONCLUSION: The risk of neuropsychiatric side effects of chloroquine and hydroxychloroquine when used for COVID-19 treatment is not known. Best practice may include suicide risk assessment for patients treated with hydroxychloroquine. However, delirium is expected to be a more likely etiology of neuropsychiatric symptoms in critically ill patients treated for COVID-19, and adjustment disorder is a much more likely etiology of anxiety and depression symptoms than the side effects of chloroquine or hydroxychloroquine.", "qid": 28, "docid": "x2be5qbi", "rank": 67, "score": 7.722599983215332}, {"content": "Title: Targeting the SARS-CoV-2 Main Protease to Repurpose Drugs for COVID-19 Content: Guided by a computational docking analysis, about 30 FDA/EMA-approved small molecule medicines were characterized on their inhibition of the SARS-CoV-2 main protease (M(Pro)). Of these tested small molecule medicines, six displayed an IC(50) value in inhibiting M(Pro) below 100 \u03bcM. Three medicines pimozide, ebastine, and bepridil are basic small molecules that are expected to exert a similar effect as hydroxychloroquine in raising endosomal pH for slowing down the SARS-CoV-2 entry into human cell hosts. Bepridil has been previously explored in a high dose as 100 mg/kg for treating diseases. Its high dose use will likely achieve dual functions in treating COVID-19 by both raising the endosomal pH to slow viral entry and inhibiting M(Pro) in infected cells. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.", "qid": 28, "docid": "fyd6coe7", "rank": 68, "score": 7.711100101470947}, {"content": "Title: Chloroquine and hydroxychloroquine for the treatment of COVID-19: A living systematic review protocol Content: OBJECTIVE: To determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.", "qid": 28, "docid": "fckn8ld4", "rank": 69, "score": 7.6504998207092285}, {"content": "Title: Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy Content: Background: Hydroxychloroquine is currently being tested as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19) in several ongoing clinical trials. Objective: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. Methods: Retrospective electronic record review, from February 27th to April 16th, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of COVID-19, confirmed or suspected, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. Results: Among 722 included subjects, 290 (40%) were receiving hydroxychloroquine. During the seven-week study period, five (1.7% [95% CI: 0.5%-4.0%] cases of COVID-19 were registered among patients with hydroxychloroquine and five (1.2% [0.4%-2.7%]) (p=0.523) in without hydroxychloroquine. COVID-19 was confirmed by PCR in one (0.3%, 95% CI 0.008-1.9%) patient with hydroxychloroquine and two (0.5%, 95% CI 0.05%-1.6%) without hydroxychloroquine (p=1.0). One patient on hydroxychloroquine and two subjects without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. Conclusions: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different. Hydroxychloroquine does not seem to be an appropriate therapy for post-exposure prophylaxis against COVID-19.", "qid": 28, "docid": "9whgh5b3", "rank": 70, "score": 7.616600036621094}, {"content": "Title: Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19 Content: PURPOSE: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. RESULTS: Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two \u2018some concerns\u2019 and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. CONCLUSIONS: Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed.", "qid": 28, "docid": "w1785lap", "rank": 71, "score": 7.589000225067139}, {"content": "Title: Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial Content: OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval \u201310.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.", "qid": 28, "docid": "3jnhboif", "rank": 72, "score": 7.573599815368652}, {"content": "Title: Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial Content: OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.", "qid": 28, "docid": "y32zotrr", "rank": 73, "score": 7.573598861694336}, {"content": "Title: Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital Content: BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission &#8804; 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1). CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.", "qid": 28, "docid": "fbnge94q", "rank": 74, "score": 7.538000106811523}, {"content": "Title: Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital Content: BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission \u2264 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1) CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.", "qid": 28, "docid": "k9aorukq", "rank": 75, "score": 7.537999153137207}, {"content": "Title: A New Drug-Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study Content: INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase\u00ae, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.", "qid": 28, "docid": "y0eb7nc0", "rank": 76, "score": 7.514200210571289}, {"content": "Title: A New Drug\u2013Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study Content: INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug\u2013drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase(\u00ae), the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as \u2018fatal outcomes\u2019. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9\u2013139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6\u201313.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.", "qid": 28, "docid": "y6peq9fh", "rank": 77, "score": 7.514199256896973}, {"content": "Title: Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis Content: Background The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) show promising SARS-CoV-2 anti-viral activity in vitro; however, clinical studies have reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin (AZ) on outcomes of COVID-19 patients. Methods We performed a systematic review and meta-analysis of studies published through July 7, 2020. We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, preprints and grey literature. We included studies that assessed COVID-19 patients treated with CQ or HCQ, with or without AZ. We pooled only adjusted effect estimates of mortality using a random effect model and estimated between studies heterogeneity using I2 statistic. We summarized the effect of CQ or HCQ on viral clearance and ICU admission/ mechanical ventilation. Results Out of 1463 citations screened for eligibility, five RCTs and 14 cohort studies were included (20,263 patients, all hospitalized but with a variable disease severity spectrum). Thirteen studies (1 RCT and 12 cohorts) with 19,573 patients examined the effect of HCQ on short term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2=0 %, p=0.647). Six cohort studies examined the effect of HCQ and AZ combination among 3430 patients. After excluding a study that examined only patients with cancers, the pooled adjusted OR was (1.15, 95% CI 0.99-1.34, I2=0.0%). Two cohort studies and three RCTs found no significant effect of HCQ on viral clearance. One RCT with 48 patients demonstrated improved viral clearance in patients treated with CQ and HCQ. Three cohort studies found that HCQ with or without AZ had no significant effect on mechanical ventilation/ ICU admission. Conclusion Moderate certainty evidence suggests that HCQ, with or without AZ, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19. Our findings are consistent with the recommendations from medical societies that HCQ should only be used to treat COVID-19 patients in the context of clinical trials. Trials of HCQ as pre-exposure prophylaxis are ongoing.", "qid": 28, "docid": "o013tpxz", "rank": 78, "score": 7.512199878692627}, {"content": "Title: The immunology of COVID-19: is immune modulation an option for treatment? Content: In December, 2019, an outbreak of COVID-19 emerged in Wuhan, China and quickly spread globally. As of May 7, 2020, there were 3 672 238 confirmed infections and 254 045 deaths attributed to COVID-19. Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0\u201324 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.", "qid": 28, "docid": "mbv45kei", "rank": 79, "score": 7.501699924468994}, {"content": "Title: Hydroxychloroquine in COVID-19 patients: what still needs to be known about the kinetics Content: Different dosage regimens of hydroxychloroquine are used to manage COVID-19 patients, without information on the pharmacokinetics in this population.Blood samples (n=101) were collected from 57 COVID-19 patients for 7 days and concentrations were compared with simulated kinetic profiles.Hydroxychloroquine exposure is low and cannot be predicted by other populations.", "qid": 28, "docid": "mmlqe2pl", "rank": 80, "score": 7.498799800872803}, {"content": "Title: Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence Content: Purpose: The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trial Registries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results: Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions: The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available. Keywords: Hydroxychloroquine, SARS-CoV-2, COVID-19, Corona virus, nCov2, systematic review", "qid": 28, "docid": "0u4ar3b5", "rank": 81, "score": 7.493000030517578}, {"content": "Title: Chloroquine paradox may cause more damage than help fight COVID-19 Content: Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.", "qid": 28, "docid": "86vzsrym", "rank": 82, "score": 7.481299877166748}, {"content": "Title: Chloroquine paradox may cause more damage than help fight COVID-19 Content: Abstract Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.", "qid": 28, "docid": "j9vmsfjw", "rank": 83, "score": 7.481298923492432}, {"content": "Title: When there is a pandemic there is no time to waste: should we have hydroxychloroquine in our armoury against COVID-19 infected patients? Content: The current use of chloroquine and/or hydroxychloroquine, a drug currently used to treat autoimmune rheumatic diseases, in treating severe acute respiratory syndrome caused by coronavirus 2 (SARSCoV-2) or COVID-19-infected patients with pneumonia is a matter of intense consideration. We wish to enter the ongoing debate as to whether this well-known drug must be given to Greek COVID-19-infected patients, especially those with pneumonia. Our arguments are based on the existing data and the capacity of the Greek health system to afford potent anti-viral treatments, which are under immense investigation. We propose several suggestions related to treatment of COVID-19 pneumonia with chloroquine/hydroxychloroquine that we think must be taken into consideration to fit the evolving situation of the pandemic in Greece.", "qid": 28, "docid": "vvexfg1c", "rank": 84, "score": 7.452899932861328}, {"content": "Title: Doubtful precipitation of hemolysis by hydroxychloroquine in glucose\u20106\u2010phosphate dehydrogenase deficient patient with COVID\u201019 infection Content: We read with great interest the recent article by Beauverd et al.(1) on an interesting case of severe hemolysis in a patient with COVID\u201019 treated with hydroxychloroquine. The authors concluded that COVID\u201019 infection was possibly the initial trigger for hemolysis. However, the article also suggested that hydroxychloroquine possibly worsened the hemolysis, and further cautioned the use of hydroxychloroquine in glucose\u20106\u2010phosphate dehydrogenase (G6PD)\u2010deficient patients. We would like to comment on the authors\u2019 attribution of accentuated hemolysis to the use of hydroxychloroquine.", "qid": 28, "docid": "b6klfi6i", "rank": 85, "score": 7.452000141143799}, {"content": "Title: Doubtful precipitation of hemolysis by hydroxychloroquine in glucose-6-phosphate dehydrogenase deficient patient with COVID-19 infection Content: We read with great interest the recent article by Beauverd et al.1 on an interesting case of severe hemolysis in a patient with COVID-19 treated with hydroxychloroquine. The authors concluded that COVID-19 infection was possibly the initial trigger for hemolysis. However, the article also suggested that hydroxychloroquine possibly worsened the hemolysis, and further cautioned the use of hydroxychloroquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient patients. We would like to comment on the authors' attribution of accentuated hemolysis to the use of hydroxychloroquine.", "qid": 28, "docid": "cl9l0sed", "rank": 86, "score": 7.451999187469482}, {"content": "Title: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study Content: COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.", "qid": 28, "docid": "fbm3zoe2", "rank": 87, "score": 7.44980001449585}, {"content": "Title: Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon. Content: Objective : To determine the early electrocardiographic changes in a cohort of ambulatory cameroonian COVID-19 patients treated with hydroxychloroquine and Azithromycin. Design : Prospective study. Setting : Treatment centres of the city of Yaounde, Cameroon, from May 7th to 24th 2020. Participants : We enrolled 51 consecutive confirmed COVID-19 on RT-PCR who having mild forms of COVID-19 and treated by hydroxychloroquine 200mg twice daily during seven days plus Azithromycin 500 mg the first day and 250 mg the remaining 4 days as per national standard. Main outcomes measures : The primary end-point was the change in QTc interval between day 0 (D0), day 3 (D3) and day 7 (D7). Secondary endpoints were changes in all other cardiac electrical conductivity patterns and the occurrence of clinical arrhythmic events during the course of treatment. Results: The population (29 men and 22 women) was aged 39 +/- 11 years (range 17 to 61 years). Mean Tisdale score was 3.35 +/- 0.48. No significant change from baseline (D0) of QTc was observed at D7 (429 +/- 27 ms at D0 versus 396 +/- 26 ms at D7; p = 0.27). A reduction of heart rate was observed between the D0 and D7 (75 +/- 13 bpm versus 70 +/- 13 bpm, p = 0.02) with increased QRS duration between D0 and D7 (95 +/- 10 ms versus 102 +/- 17 ms, p = 0.004). No symptomatic arrhythmic events occurred during the treatment course. Conclusions: No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with hydroxychloroquine and azithromycin. Studies are needed in critical-ill and older patients.", "qid": 28, "docid": "jungqwi9", "rank": 88, "score": 7.447000026702881}, {"content": "Title: Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial Content: OBJECTIVES: In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. TRIAL DESIGN: This is a multi-centre, two-arm, parallel-group, triple-blind, phase 2-3 randomised controlled trial. PARTICIPANTS: All patients over the age of 15 from 5 types of cancer are included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin's lymphoma treated with leukemia protocols and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study. The exclusion criteria will include known sensitivity to Hydroxychloroquine, weight below 35 kilograms, history of retinopathy, history of any cardiac disease, acute respiratory tract infection in the last 2 months, having COVID-19 in the first two weeks of entering the trial, having Diabetes Mellitus, having an immuno-suppressive disease other than cancer, having chronic pulmonary disease and taking immuno-suppressant drug other than chemotherapeutic agents for current cancer. This study is performed in five academic centres affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to two groups; one being given hydroxychloroquine and the other is given placebo. During two months of treatment, the two groups are treated with either hydroxychloroquine (Amin\u00ae Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, colour, smell) as a single 200 mg tablet every other day. Patients will be monitored for COVID-19 symptoms during the follow-up period. If signs or symptoms occur (fever, cough, shortness of breath), they will be examined and investigated with a high-resolution computed tomography (CT) scan of the lungs, COVID-19 specific IgM, IgG antibody assay and a nucleic acid amplification test (NAT) for the SARS-CoV-2 virus. MAIN OUTCOMES: The primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer over a 2-month period. RANDOMISATION: Randomisation will be performed using randomly permuted blocks. By using an online website (www.randomization.com) the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1. BLINDING (MASKING): Participants and caregivers do not know whether the patient is in the intervention or the control group. The outcome assessor and the data analyst are also blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 60 patients, with 30 patients in each group. TRIAL STATUS: The trial began on April 14, 2020 and recruitment is ongoing. Recruitment is anticipated to be completed by June 14, 2020 There has been no change in study protocol since approval, protocol version 1 was approved April 12, 2020. TRIAL REGISTRATION: This trial has been registered by the title of \"Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment\" in Iranian Registry of Clinical Trials (IRCT) with code \"IRCT20200405046958N1\", https://www.irct.ir/trial/46946. Registration date is April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 28, "docid": "dge5v6gj", "rank": 89, "score": 7.430600166320801}, {"content": "Title: Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial Content: OBJECTIVES: In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. TRIAL DESIGN: This is a multi-centre, two-arm, parallel-group, triple-blind, phase 2-3 randomised controlled trial. PARTICIPANTS: All patients over the age of 15 from 5 types of cancer are included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin's lymphoma treated with leukemia protocols and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study. The exclusion criteria will include known sensitivity to Hydroxychloroquine, weight below 35 kilograms, history of retinopathy, history of any cardiac disease, acute respiratory tract infection in the last 2 months, having COVID-19 in the first two weeks of entering the trial, having Diabetes Mellitus, having an immuno-suppressive disease other than cancer, having chronic pulmonary disease and taking immuno-suppressant drug other than chemotherapeutic agents for current cancer. This study is performed in five academic centres affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to two groups; one being given hydroxychloroquine and the other is given placebo. During two months of treatment, the two groups are treated with either hydroxychloroquine (Amin\u00ae Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, colour, smell) as a single 200 mg tablet every other day. Patients will be monitored for COVID-19 symptoms during the follow-up period. If signs or symptoms occur (fever, cough, shortness of breath), they will be examined and investigated with a high-resolution computed tomography (CT) scan of the lungs, COVID-19 specific IgM, IgG antibody assay and a nucleic acid amplification test (NAT) for the SARS-CoV-2 virus. MAIN OUTCOMES: The primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer over a 2-month period. RANDOMISATION: Randomisation will be performed using randomly permuted blocks. By using an online website (www.randomization.com) the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1. BLINDING (MASKING): Participants and caregivers do not know whether the patient is in the intervention or the control group. The outcome assessor and the data analyst are also blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 60 patients, with 30 patients in each group. TRIAL STATUS: The trial began on April 14, 2020 and recruitment is ongoing. Recruitment is anticipated to be completed by June 14, 2020 There has been no change in study protocol since approval, protocol version 1 was approved April 12, 2020. TRIAL REGISTRATION: This trial has been registered by the title of \u201cEffect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment\u201d in Iranian Registry of Clinical Trials (IRCT) with code \u201cIRCT20200405046958N1\u201d, https://www.irct.ir/trial/46946. Registration date is April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 28, "docid": "eikz07zz", "rank": 90, "score": 7.430599212646484}, {"content": "Title: Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 Content: Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.", "qid": 28, "docid": "2u5zxc2i", "rank": 91, "score": 7.426199913024902}, {"content": "Title: Coronavirus disease-2019 in cancer patients. A report of the first 25 cancer patients in a western country (Italy) Content: Background: We describe cancer patients with coronavirus disease-2019 (COVID-19) infection treated at the Piacenza\u2019s general hospital (north Italy). Materials & methods: Twenty-five cancer patients infected by COVID-19 admitted at the Piacenza\u2019s general hospital from 21 February to 18 March 2020. Outcome from the infection were compared with infected noncancer patients. Results: Twenty patients (80%) were treated with antiviral therapy and hydroxychloroquine and five (20%) received hydroxychloroquine alone. Nine (36%) patients died, while 16 (64%) overcome the infection. In the control group the mortality was 16.13% and the overcome from infection was 83.87%. Conclusion: Mortality for COVID-19 was greater in cancer patients when compared with noncancer patients, worse prognosis for older age, women and patients treated with hydroxychloroquine alone. However, the comparisons did not reach statistical significance in most cases. This could be due to the small sample size that is the main limitation of the study.", "qid": 28, "docid": "2zq3ej38", "rank": 92, "score": 7.424900054931641}, {"content": "Title: Coronavirus disease-2019 in cancer patients. A report of the first 25 cancer patients in a western country (Italy) Content: Background: We describe cancer patients with coronavirus disease-2019 (COVID-19) infection treated at the Piacenza's general hospital (north Italy). Materials & methods: 25 cancer patients infected by COVID-19 admitted at the Piacenza's general hospital from 21 February to 18 March 2020. Outcome from the infection were compared with infected noncancer patients. Results: 20 patients (80%) were treated with antiviral therapy and hydroxychloroquine and five (20%) received hydroxychloroquine alone. Nine (36%) patients died, while 16 (64%) overcome the infection. In the control group the mortality was 16.13% and the overcome from infection was 83.87%. Conclusion: Mortality for COVID-19 was greater in cancer patients when compared with noncancer patients, worse prognosis for older age, women and patients treated with hydroxychloroquine alone. However, the comparisons did not reach statistical significance in most cases. This could be due to the small sample size that is the main limitation of the study.", "qid": 28, "docid": "vovj72ep", "rank": 93, "score": 7.424899101257324}, {"content": "Title: Systematic Review and Meta-analysis of the Effectiveness and Safety of Hydroxychloroquine in COVID-19. Content: Backgrounds. Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis. Methods. A thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other. Results. Five trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin. However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients. Conclusion. The use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective. The combination of hydroxychloroquine and azithromycin has shown synergic effects. However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.", "qid": 28, "docid": "2f6nj4to", "rank": 94, "score": 7.39739990234375}, {"content": "Title: COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: OBJECTIVES/BACKGROUND AND OBJECTIVES: Prior epidemics of high-mortality human coronaviruses, such as the acute respiratory syndrome coronavirus (SARS-CoV or SARS-1) in 2003, have driven the characterization of compounds that could be possibly active against the currently emerging novel coronavirus SARS-CoV-2 (COVID-19). Presently, no approved treatment or prophylaxis is available for COVID-19. We comment on the existing COVID-19 research methodologies in general and the published reporting. Given the media attention and claims of effectiveness, we chose chloroquine and hydroxychloroquine, in combination with azithromycin, as an area of COVID-19 research to examine. METHODS/STUDY DESIGN AND SETTING: MEDLINE and EMBASE electronic databases were searched from 2019 to present (April 3rd, 2020) using a mix of keywords such as COVID-19 and chloroquine and hydroxychloroquine. We also searched the largest clinical medicine preprint repository, medRxiv.org. RESULTS: We found 6 studies, 3 randomized control trials and 3 observational studies, focusing on chloroquine and hydroxychloroquine (with azithromycin). We critically appraised the evidence. CONCLUSION: We found that the COVID-19 research methodology is very poor in the area of chloroquine/hydroxychloroquine research. In screening the literature, we observed the same across COVID-19 research in relation to potential treatments. The reporting is very poor and sparse, and patient-important outcomes needed to discern decision-making priorities are not reported. We do understand the barriers to perform rigorous research in health care settings overwhelmed by a novel deadly disease. However, this emergency pandemic situation does not transform flawed methods and data into credible results. The adequately powered, comparative, and robust clinical research that is needed for optimal evidence-informed decision-making remains absent in COVID-19.", "qid": 28, "docid": "5w1q57v2", "rank": 95, "score": 7.393599987030029}, {"content": "Title: Chloroquine and hydroxychloroquine in the management of COVID-19: Much kerfuffle but little evidence Content: Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "qid": 28, "docid": "gjmvw8l2", "rank": 96, "score": 7.376399993896484}, {"content": "Title: Chloroquine and hydroxychloroquine in the management of COVID-19: much kerfuffle but little evidence Content: Summary Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "qid": 28, "docid": "pdvqdgsw", "rank": 97, "score": 7.376399040222168}, {"content": "Title: Safety considerations of chloroquine and hydroxychloroquine in treatment of COVID-19 Content: Chloroquine and hydroxychloroquine are both used to treat COVID-19. Safety data in this specific population is largely unknown. In particular, cardiologic, gastro-intestinal and neuropsychiatric side-effects of (hydroxychloroquine) needs special attention in COVID-19 patients.", "qid": 28, "docid": "b5fel2d3", "rank": 98, "score": 7.3678998947143555}, {"content": "Title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Content: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: \u00e2\u0080\u00a2 There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: \u00e2\u0080\u00a2 Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. \u00e2\u0080\u00a2 However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.", "qid": 28, "docid": "u7arfoym", "rank": 99, "score": 7.3643999099731445}, {"content": "Title: Plasma IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients Content: Intensive Care Unit (ICU) admissions and mortality in severe COVID-19 patients are driven by cytokine storms and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays superior 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. Among 16 patients with plasma IL-6 measurement post-corticosteroid administration, a higher proportion of patients with an IL-6 value over 10 pg/mL have worse outcomes (i.e. ICU Length of Stay > 15 days or death) when compared to 41 patients treated with non-corticosteroid drugs including antivirals, tocilizumab, azithromycin, and hydroxychloroquine (p-value = 0.0024). Given this unexpected clinical association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the Glucocorticoid Receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single cell RNA-seq data from bronchoalveolar lavage fluid of severe COVID-19 patients and nearly 2 million human cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express both NR3C1 and IL-6. The mechanism of Glucocorticoid Receptor (GR) agonists mitigating pulmonary and multi-organ inflammation in some COVID-19 patients with respiratory failure, may be in part due to their successful antagonism of IL-6 production within lung macrophages and vasculature.", "qid": 28, "docid": "4ipq7bd4", "rank": 100, "score": 7.362100124359131}]}
{"query": "which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information?", "hits": [{"content": "Title: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 Content: Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV\u2013host interactome and drug targets in the human protein\u2013protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV\u2013host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the \u201cComplementary Exposure\u201d pattern: the targets of the drugs both hit the HCoV\u2013host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.", "qid": 29, "docid": "4yuw7jo3", "rank": 1, "score": 25.906600952148438}, {"content": "Title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Content: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption(1,2). There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.", "qid": 29, "docid": "38d6gb7o", "rank": 2, "score": 25.449399948120117}, {"content": "Title: Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study Content: Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shape-based screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "7wjd740p", "rank": 3, "score": 25.193599700927734}, {"content": "Title: Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study Content: Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shape-based screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "d6jt1dal", "rank": 4, "score": 25.1935977935791}, {"content": "Title: Network-based Drug Repurposing for Human Coronavirus Content: Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.", "qid": 29, "docid": "b4mdiont", "rank": 5, "score": 24.871000289916992}, {"content": "Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Content: A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "qid": 29, "docid": "7qd8z5e7", "rank": 6, "score": 24.53820037841797}, {"content": "Title: Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19 Content: The rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs that can help contain the outbreak. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered as a potential target for drug development. Based on in silico screening followed by in vitro studies, here we report that the existing FDA-approved Bcr-Abl tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 with an IC50 of 130 nM. We provide initial evidence that inhibition of virus fusion may explain the antiviral action of imatinib. This finding is significant since pinpointing the mode of action allows evaluating the drug\u2019s affinity to the SARS-CoV-2-specific target protein, and in turn, helps make inferences on the potency of the drug and evidence-based recommendations on its dosage. To this end, we provide evidence that imatinib binds to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein with an affinity at micromolar, i.e., 2.32 \u00b1 0.9 \u00b5M, levels. We also show that imatinib inhibits other coronaviruses, SARS-CoV and MERS-CoV, possibly via fusion inhibition. Based on promising in vitro results, we propose the Abl kinase inhibitor (ATKI), imatinib, to be a viable repurposable drug candidate for further clinical validation against COVID-19.", "qid": 29, "docid": "nnv2e7gr", "rank": 7, "score": 24.420299530029297}, {"content": "Title: Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing Content: Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It was first identified in Wuhan, China, and has since spread causing a global pandemic. Various studies have been performed to understand the molecular mechanisms of viral infection for predicting drug repurposing candidates. However, such information is spread across many publications and it is very time-consuming to access, integrate, explore, and exploit. We developed CoVex, the first interactive online platform for SARS-CoV-2 and SARS-CoV-1 host interactome exploration and drug (target) identification. CoVex integrates 1) experimentally validated virus-human protein interactions, 2) human protein-protein interactions and 3) drug-target interactions. The web interface allows user-friendly visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drugs. Thus, CoVex is an important resource, not only to understand the molecular mechanisms involved in SARS-CoV-2 and SARS-CoV-1 pathogenicity, but also in clinical research for the identification and prioritization of candidate therapeutics. We apply CoVex to investigate recent hypotheses on a systems biology level and to systematically explore the molecular mechanisms driving the virus life cycle. Furthermore, we extract and discuss drug repurposing candidates involved in these mechanisms. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms integrating virus-host-drug interactions. It is available at https://exbio.wzw.tum.de/covex/.", "qid": 29, "docid": "7cjm2yp0", "rank": 8, "score": 24.319700241088867}, {"content": "Title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Content: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be \u223c2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of \u223c6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found \u223c50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 \u2264 50 \u03bcM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 \u03bcM), Ciluprevir (20.77\u03bcM). Narlaprevir (IC50=1.10\u03bcM), and Telaprevir (15.25\u03bcM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.", "qid": 29, "docid": "slouuryl", "rank": 9, "score": 24.183300018310547}, {"content": "Title: Computational target-based drug repurposing of elbasvir, an antiviral drug predicted to bind multiple SARS-CoV-2 proteins. Content: Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome caused by SARS-CoV-2 (2019-nCoV). While no drugs have yet been approved to treat this disease, small molecules effective against other viral infections are under clinical evaluation for therapeutic abatement of SARS-CoV-2 infections. Ongoing clinical trials include Kaletra (a combination of two protease inhibitors approved for HIV treatment), remdesivir (an investigational drug targeting RNA-dependent RNA polymerase [RdRP] of SARS-CoV-2), and hydroxychloroquine (an approved anti-malarial and immuno-modulatory drug). Since SARS-CoV-2 replication depends on three virally encoded proteins (RdRP, papain-like proteinase, and helicase), we screened 54 FDA-approved antiviral drugs and ~3300 investigational drugs for binding to these proteins using targeted and unbiased docking simulations and computational modeling. Elbasvir, a drug approved for treating hepatitis C, is predicted to bind stably and preferentially to all three proteins. At the therapeutic dosage, elbasvir has low toxicity (liver enzymes transiently elevated in 1% of subjects) and well-characterized drug-drug interactions. We predict that treatment with elbasvir, alone or in combination with other drugs such as grazoprevir, could efficiently block SARS-CoV-2 replication. The concerted action of elbasvir on at least three targets essential for viral replication renders viral mutation to drug resistance extremely unlikely.", "qid": 29, "docid": "kc2r034w", "rank": 10, "score": 23.866300582885742}, {"content": "Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Content: The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "qid": 29, "docid": "eje3i558", "rank": 11, "score": 23.555500030517578}, {"content": "Title: Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19 Content: The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (M(pro)), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for M(pro), we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against M(pro). In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed for subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the M(pro) catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.", "qid": 29, "docid": "wg1rshzk", "rank": 12, "score": 23.502899169921875}, {"content": "Title: Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19 Content: The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed to subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.", "qid": 29, "docid": "wu6nf38u", "rank": 13, "score": 23.502897262573242}, {"content": "Title: Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection Content: SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (\u2212) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (\u2212) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (\u2212) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.", "qid": 29, "docid": "l7ohbk7c", "rank": 14, "score": 23.279600143432617}, {"content": "Title: Identifying Human Interactors of SARS-CoV-2 Proteins and Drug Targets for COVID-19 using Network-Based Label Propagation Content: Motivated by the critical need to identify new treatments for COVID-19, we present a genome-scale, systems-level computational approach to prioritize drug targets based on their potential to regulate host-virus interactions or their downstream signaling targets. We adapt and specialize network label propagation methods to this end. We demonstrate that these techniques can predict human-SARS-CoV-2 protein interactors with high accuracy. The top-ranked proteins that we identify are enriched in host biological processes that are potentially coopted by the virus. We present cases where our methodology generates promising insights such as the potential role of HSPA5 in viral entry. We highlight the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. We identify tubulin proteins involved in ciliary assembly that are targeted by anti-mitotic drugs. Drugs that we discuss are already undergoing clinical trials to test their efficacy against COVID-19. Our prioritized list of human proteins and drug targets is available as a general resource for biological and clinical researchers who are repositioning existing and approved drugs or developing novel therapeutics as anti-COVID-19 agents.", "qid": 29, "docid": "qrfx165d", "rank": 15, "score": 23.220800399780273}, {"content": "Title: Genetic architecture of host proteins interacting with SARS-CoV-2 Content: Strategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid \u2018in silico\u2019 assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01\u201349.9%) and explaining 0.3\u201370.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).", "qid": 29, "docid": "k0dzrgtx", "rank": 16, "score": 23.05900001525879}, {"content": "Title: Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19 Content: SARS-CoV-2 is causative agent of COVID-19, which is responsible for severe social and economic disruption globally. Lack of vaccine or antiviral drug with clinical efficacy suggested that drug repurposing approach may provide a quick therapeutic solution to COVID-19. Nonstructural protein-15 (NSP15) encodes for an uridylate-specific endoribonuclease (EndoU) enzyme, essential for virus life cycle and an attractive target for drug development. We have performed in silico based virtual screening of FDA approved compounds targeting EndoU in search of COVID-19 drugs from commercially available approved molecules. Two drugs Glisoxepide and Idarubicin used for treatment for diabetes and leukemia, respectively, were selected as stronger binder of EndoU. Both the drugs bound to the active site of the viral endonuclease by forming attractive intermolecular interactions with catalytically essential amino acid residues, His235, His250, and Lys290. Molecular dynamics simulation studies showed stable conformation dynamics upon drugs binding to endoU. The binding free energies for Glisoxepide and Idarubicin were calculated to be -141 \u00b1 11 and -136 \u00b1 16 kJ/mol, respectively. The IC50 were predicted to be 9.2 \u00b5M and 30 \u00b5M for Glisoxepide and Idarubicin, respectively. Comparative structural analysis showed the stronger binding of EndoU to Glisoxepide and Idarubicin than to uridine monophosphate (UMP). Surface area calculations showed buried are of 361.8\u00c52 by Glisoxepide which is almost double of the area occupied by UMP suggesting stronger binding of the drug than the ribonucleotide. However, further studies on these drugs for evaluation of their clinical efficacy and dose formulations may be required, which may provide a quick therapeutic option to treat COVID-19. Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "jbjve8cg", "rank": 17, "score": 23.035999298095703}, {"content": "Title: Virtual Screening of Plant Metabolites against Main protease, RNA-dependent RNA polymerase and Spike protein of SARS-CoV-2: Therapeutics option of COVID-19 Content: Covid-19, a serious respiratory complications caused by SARS-CoV-2 has become one of the global threat to human healthcare system. The present study evaluated the possibility of plant originated approved 117 therapeutics against the main protease protein (MPP), RNA-dependent RNA polymerase (RdRp) and spike protein (S) of SARS-CoV-2 including drug surface analysis by using molecular docking through drug repurposing approaches. The molecular interaction study revealed that Rifampin (-16.3 kcal/mol) were topmost inhibitor of MPP where Azobechalcone were found most potent plant therapeutics for blocking the RdRp (-15.9 kcal /mol) and S (-14.4 kcal/mol) protein of SARS-CoV-2. After the comparative analysis of all docking results, Azobechalcone, Rifampin, Isolophirachalcone, Tetrandrine and Fangchinoline were exhibited as the most potential inhibitory plant compounds for targeting the key proteins of SARS-CoV-2. However, amino acid positions; H41, C145, and M165 of MPP played crucial roles for the drug surface interaction where F368, L371, L372, A375, W509, L514, Y515 were pivotal for RdRP. In addition, the drug interaction surface of S proteins also showed similar patterns with all of its maximum inhibitors. ADME analysis also strengthened the possibility of screened plant therapeutics as the potent drug candidates against SARS-C with the highest drug friendliness.", "qid": 29, "docid": "oyc2djxk", "rank": 18, "score": 23.00819969177246}, {"content": "Title: Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19 Content: SARS-CoV-2 is causative agent of COVID-19, which is responsible for severe social and economic disruption globally. Lack of vaccine or antiviral drug with clinical efficacy suggested that drug repurposing approach may provide a quick therapeutic solution to COVID-19. Nonstructural protein-15 (NSP15) encodes for an uridylate-specific endoribonuclease (EndoU) enzyme, essential for virus life cycle and an attractive target for drug development. We have performed in silico based virtual screening of FDA approved compounds targeting EndoU in search of COVID-19 drugs from commercially available approved molecules. Two drugs Glisoxepide and Idarubicin used for treatment for diabetes and leukemia, respectively, were selected as stronger binder of EndoU. Both the drugs bound to the active site of the viral endonuclease by forming attractive intermolecular interactions with catalytically essential amino acid residues, His235, His250, and Lys290. Molecular dynamics simulation studies showed stable conformation dynamics upon drugs binding to endoU. The binding free energies for Glisoxepide and Idarubicin were calculated to be \u2013141 \u00b1 11 and \u2013136 \u00b1 16 kJ/mol, respectively. The IC(50) were predicted to be 9.2 \u00b5M and 30 \u00b5M for Glisoxepide and Idarubicin, respectively. Comparative structural analysis showed the stronger binding of EndoU to Glisoxepide and Idarubicin than to uridine monophosphate (UMP). Surface area calculations showed buried are of 361.8\u00c5(2) by Glisoxepide which is almost double of the area occupied by UMP suggesting stronger binding of the drug than the ribonucleotide. However, further studies on these drugs for evaluation of their clinical efficacy and dose formulations may be required, which may provide a quick therapeutic option to treat COVID-19. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "9cblzv98", "rank": 19, "score": 22.85449981689453}, {"content": "Title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs Content: Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options.", "qid": 29, "docid": "2lmwnfda", "rank": 20, "score": 22.77829933166504}, {"content": "Title: Prioritisation of potential anti-SARS-CoV-2 drug repurposing opportunities based on ability to achieve adequate target site concentrations derived from their established human pharmacokinetics Content: Many papers are emerging that describe the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, no comprehensive evaluation of these molecules in the context of the achievable plasma pharmacokinetics after administration of approved doses and schedules to humans has been conducted. Moreover, most publications have focussed on 50% maximum effective concentrations (EC50), which may be an insufficiently robust indicator of antiviral activity because of marked differences in the slope of the concentration-response curve between drugs. Accordingly, in vitro anti-SARS-CoV-2 activity data was digitised from all available publications up to 13th April 2020 and used to recalculate an EC90 value for each drug. EC90 values were then expressed as a ratio to the achievable maximum plasma concentrations (Cmax) reported for each drug after administration of the approved dose to humans (Cmax/EC90 ratio). Only 14 of the analysed drugs achieved a Cmax/EC90 ratio above 1 meaning that plasma Cmax concentrations exceeded those necessary to inhibit 90% of SARS-CoV-2 replication. A more in-depth assessment of these drugs demonstrated that only nitazoxanide, nelfinavir, tipranavir (boosted with ritonavir) and sulfadoxine achieved plasma concentrations above their anti-SARS-CoV-2 activity across their entire approved dosing interval at their approved human dose. For all drugs reported, the unbound lung to plasma tissue partition coefficient (KpUlung) was also simulated and used along with reported Cmax and fraction unbound in plasma to derive a lung Cmax/EC50 as a better indicator of potential human efficacy (lung Cmax/EC90 ratio was also calculable for a limited number of drugs). Using this parameter hydroxychloroquine, chloroquine, mefloquine, atazanavir (boosted with ritonavir), tipranavir (boosted with ritonavir), ivermectin, azithromycin and lopinavir (boosted with ritonavir) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50. This analysis was not possible for nelfinavir because insufficient data were available to calculate KpUlung but nitozoxanide and sulfadoxine were also predicted to exceed their reported EC50 by 3.1- and 1.5-fold in lung, respectively. The antiviral activity data reported to date is of variable quality and conducted under different conditions by different investigators. However, this analysis has prioritised candidates with the best chance for success in therapy or chemoprevention of Covid-19 based upon the currently available in vitro activity and human plasma pharmacokinetic data. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.", "qid": 29, "docid": "untuy1e6", "rank": 21, "score": 22.76129913330078}, {"content": "Title: Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics Content: Rapidly spreading viral pandemics, such as those caused by influenza and SAR-CoV-2 (COVID19), require rapid action and the fastest way to combat this challenge is by repurposing existing drugs as anti-viral therapeutics. Here we first show that human organ-on-a-chip (Organ Chip) microfluidic culture devices lined by a highly differentiated, primary, human lung airway epithelium cultured under an air-liquid interface and fed by continuous medium flow can be used to model virus entry, replication, strain-dependent virulence, host cytokine production, and recruitment of circulating immune cells in response to infection by influenza, as well as effects of existing and novel therapeutics. These Airway Chips, which contain human lung epithelial cells that express high levels of ACE2 and TMPRSS2, were then used to assess the inhibitory activities of 7 clinically approved drugs (chloroquine, arbidol, toremifene, clomiphene, amodiaquine, verapamil, and amiodarone) that we found inhibit infection by viral pseudoparticles expressing SARS-CoV-2 spike protein in human Huh-7 cells, and others recently showed suppress infection by native SARS-CoV-2 in Vero cells. However, when these drugs were administered under flow at the maximal concentration in blood reported in clinical studies in human Airway Chips, only two of these drugs \u2014 amodiaquine and toremifene \u2014 significantly inhibited entry of the pseudotyped SARS-CoV-2 virus. This work suggests that human Organ Chip technology may be used in conjunction with existing rapid cell-based screening assays to study human disease pathogenesis and expedite drug repurposing in biothreat crises caused by pandemic viruses.", "qid": 29, "docid": "mrgw2mnx", "rank": 22, "score": 22.664199829101562}, {"content": "Title: Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs. Content: Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.", "qid": 29, "docid": "gwm36n75", "rank": 23, "score": 22.585899353027344}, {"content": "Title: Molecular docking and binding mode analysis of selected FDA approved drugs against COVID-19 selected key protein targets: An effort towards drug repurposing to identify the combination therapy to combat COVID-19 Content: The emergence of COVID-19 has severely compromised the arsenal of antiviral and antibiotic drugs. Drug discovery is a multistep process with a high failure rate, high cost and it takes approximately 10-12 years for the development of new molecules into the clinical candidate. On the other side, drug repurposing also called old drugs for new uses, is an attractive alternative approach for a new application of marketed FDA approved or investigational drugs. In the current pandemic situation raised due to COVID-19, repurposing of existing FDA approved drugs are emerging as the first line of the treatment. The causative viral agent of this highly contagious disease and acute respiratory syndrome coronavirus (SARS-CoV) shares high nucleotide similarity. Therefore, many existing viral targets are structurally expected to be similar to SARS-CoV and likely to be inhibited by the same compounds. Here, we selected three viral key proteins based on their vital role in viral life cycle: ACE2 (helps in entry into the human host), viral nonstructural proteins RNA-dependent RNA polymerase (RdRp) NSP12, and NSP16 which helps in replication, and viral latency (invasion from immunity). The FDA approved drugs chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV) and arbidol (ABD) are emerging as promising agents to combat COVID-19. Our hypothesis behind the docking studies is to determine the binding affinities of these drugs and identify the key amino acid residues playing a key role in their mechanism of action. The docking studies were carried out through Autodock and online COVID-19 docking server. Further studies on a broad range of FDA approved drugs including few more protein targets, molecular dynamics studies, in-vitro and in-vivo biological evaluation are required to identify the combination therapy targeting various stages of the viral life cycle.", "qid": 29, "docid": "vnn7lp8w", "rank": 24, "score": 22.506900787353516}, {"content": "Title: Targeting ACE2-RBD interaction as a platform for COVID19 therapeutics: Development and drug repurposing screen of an AlphaLISA proximity assay Content: The COVID-19 pandemic, caused by SARS-CoV-2, is a pressing public health emergency garnering rapid response from scientists across the globe. Host cell invasion is initiated through direct binding of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Disrupting the spike-ACE2 interaction is a potential therapeutic target for treating COVID-19. We have developed a proximity-based AlphaLISA assay to measure binding of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) to ACE2. Utilizing this assay platform, a drug-repurposing screen against 3,384 small molecule drugs and pre-clinical compounds was performed, yielding 25 high-quality, small-molecule hits that can be evaluated in cell-based models. This established AlphaLISA RBD-ACE2 platform can facilitate evaluation of biologics or small molecules that can perturb this essential viral-host interaction to further the development of interventions to address the global health pandemic.", "qid": 29, "docid": "wz2wrgpk", "rank": 25, "score": 22.49970054626465}, {"content": "Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded &#945;-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.", "qid": 29, "docid": "gykudnxf", "rank": 26, "score": 22.489999771118164}, {"content": "Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded \u03b1-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M(pro) (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 M(pro) for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 M(pro) active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M(pro) protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.", "qid": 29, "docid": "hgpfib1z", "rank": 27, "score": 22.48999786376953}, {"content": "Title: Pharmacodynamics and Systems Pharmacology Approaches to Repurposing Drugs in the Wake of Global Health Burden Content: Abstract There are emergent needs for cost-effective treatment worldwide, for which repurposing to develop a drug with existing marketing approval of disease(s) for new disease(s) is a valid option. Although strategic mining of electronic health records has produced real-world evidences to inform drug repurposing, using omics data (drug and disease), knowledge base of protein interactions, and database of transcription factors have been explored. Structured integration of all the existing data under the framework of drug repurposing will facilitate decision making. The ability to foresee the need to integrate new data types produced by emergent technologies and to enable data connectivity in the context of human biology and targeted diseases, as well as to use the existing crucial quality data of all approved drugs will catapult the number of drugs being successfully repurposed. However, translational pharmacodynamics databases for modeling information across human biology in the context of host factors are lacking and are critically needed for drug repurposing to improve global public health, especially for the efforts to combat neglected tropic diseases as well as emergent infectious diseases such as Zika or Ebola virus.", "qid": 29, "docid": "j5nmifhj", "rank": 28, "score": 22.478500366210938}, {"content": "Title: Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy Content: Due to the lack of efficient therapeutic options and clinical trial limitations, the FDA-approved drugs can be a good choice to handle Coronavirus disease (COVID-19). Many reports have enough evidence for the use of FDA-approved drugs which have inhibitory potential against target proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we utilized a structure-based drug design approach to find possible drug candidates from the existing pool of FDA-approved drugs and checked their effectiveness against the SARS-CoV-2. We performed virtual screening of the FDA-approved drugs against the main protease (Mpro) of SARS-CoV-2, an essential enzyme, and a potential drug target. Using well-defined computational methods, we identified Glecaprevir and Maraviroc (MVC) as the best inhibitors of SARS-CoV-2 Mpro. Both drugs bind to the substrate-binding pocket of SARS-CoV-2 Mpro and form a significant number of non-covalent interactions. Glecaprevir and MVC bind to the conserved residues of substrate-binding pocket of SARS-CoV-2 Mpro. This work provides sufficient evidence for the use of Glecaprevir and MVC for the therapeutic management of COVID-19 after experimental validation and clinical manifestations.", "qid": 29, "docid": "k4dphhfh", "rank": 29, "score": 22.461000442504883}, {"content": "Title: Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy Content: Due to the lack of efficient therapeutic options and clinical trial limitations, the FDA-approved drugs can be a good choice to handle Coronavirus disease (COVID-19). Many reports have enough evidence for the use of FDA-approved drugs which have inhibitory potential against target proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we utilized a structure-based drug design approach to find possible drug candidates from the existing pool of FDA-approved drugs and checked their effectiveness against the SARS-CoV-2. We performed virtual screening of the FDA-approved drugs against the main protease (M(pro)) of SARS-CoV-2, an essential enzyme, and a potential drug target. Using well-defined computational methods, we identified Glecaprevir and Maraviroc (MVC) as the best inhibitors of SARS-CoV-2 M(pro). Both drugs bind to the substrate-binding pocket of SARS-CoV-2 M(pro) and form a significant number of non-covalent interactions. Glecaprevir and MVC bind to the conserved residues of substrate-binding pocket of SARS-CoV-2 M(pro). This work provides sufficient evidence for the use of Glecaprevir and MVC for the therapeutic management of COVID-19 after experimental validation and clinical manifestations.", "qid": 29, "docid": "rz205rqd", "rank": 30, "score": 22.46099853515625}, {"content": "Title: The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2 Content: The mapping of SARS-CoV-2 human protein-protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host-virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "qid": 29, "docid": "2cvvkrx9", "rank": 31, "score": 22.316999435424805}, {"content": "Title: The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2 Content: The mapping of SARS-CoV-2 human protein\u2013protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host\u2013virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "qid": 29, "docid": "uuy94dwa", "rank": 32, "score": 22.316997528076172}, {"content": "Title: Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening Content: Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \"up\" to \"down\" conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "qid": 29, "docid": "5vgfliv0", "rank": 33, "score": 22.308900833129883}, {"content": "Title: Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening Content: Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \u201cup\u201d to \u201cdown\u201d conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below \u20138.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "qid": 29, "docid": "74xvvwrw", "rank": 34, "score": 22.30889892578125}, {"content": "Title: Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein Content: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection.", "qid": 29, "docid": "ogiicyik", "rank": 35, "score": 22.260499954223633}, {"content": "Title: Repurposing low\u2013molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2 Content: The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low\u2013molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low\u2013molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.", "qid": 29, "docid": "dpble2jd", "rank": 36, "score": 22.255399703979492}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "rvzgut4w", "rank": 37, "score": 22.235700607299805}, {"content": "Title: Docking study of chloroquine and hydroxychloroquine interaction with RNA binding domain of nucleocapsid phospho-protein - an in silico insight into the comparative efficacy of repurposing antiviral drugs Content: Recent outbreak of novel Coronavirus disease () pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and its N terminal domain (NTD) of Nucleocapsid protein (N protein) binds to the viral (+) sense RNA and results in virus ribonucleoprotien complex, essential for the virus replication. The N protein is composed of a serine-rich linker region sandwiched between NTD and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. Therefore, there is always a quest to target RNA binding domain of nucleocapsid phosphoprotein (NTD-N-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the NTD-N-protein of SARS-CoV-2. With the help of various computational methods, we have explored the potential role of both of these antiviral drugs for the treatment of patients by comparing the efficacy of both of the drugs to bind to NTD-N-protein. In our research Hydroxychloroquine exhibited potential inhibitory effects of NTD-N-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with . Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with . We further hypothesize that the comparative NTD-N-protein -drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "us0qpw0m", "rank": 38, "score": 22.232099533081055}, {"content": "Title: Potentially repurposable drugs for COVID-19 identified from SARS-CoV-2 Host Protein Interactome Content: We previously presented the protein-protein interaction network - the \u2018HoP\u2019 or the host protein interactome - of 332 host proteins that were identified to interact with 27 nCoV19 viral proteins by Gordon et al. Here, we studied drugs targeting the proteins in this interactome to identify whether any of them may potentially be repurposable against SARS-CoV-2. We studied each of the drugs using the BaseSpace Correlation Engine and identified those that induce gene expression profiles negatively correlated with SARS-associated expression profile. This analysis resulted in 20 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for SARS (viral infection versus normal). These included drugs that were already being tested for their clinical activity against SARS-CoV-2, those with proven activity against SARS-CoV/MERS-CoV, broad-spectrum antiviral drugs, and those identified/prioritized by other computational re-purposing studies. In summary, our integrated computational analysis of the HoP interactome in conjunction with drug-induced transcriptomic data resulted in drugs that may be repurposable for COVID-19.", "qid": 29, "docid": "yv2gjjzg", "rank": 39, "score": 22.2278995513916}, {"content": "Title: State-of-the-art tools unveil potent drug targets amongst clinically approved drugs to inhibit helicase in SARS-CoV-2 Content: INTRODUCTION: The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating coronavirus disease 2019 (COVID-19). The present state-of-the-art tool-based screening was targeted to identify drug targets among clinically approved drugs by uncovering SARS-CoV-2 helicase inhibitors through molecular docking analysis. MATERIAL AND METHODS: Helicase is a vital viral replication enzyme, which unwinds nucleic acids and separates the double-stranded nucleic acids into single-stranded nucleic acids. Hence, the SARS-CoV-2 helicase protein 3D structure was predicted, validated, and used to screen the druggable targets among clinically approved drugs such as protease inhibitor, nucleoside reverse transcriptase inhibitor, and non-nucleoside reverse transcriptase inhibitors, used to treat HIV infection using molecular docking analysis. RESULTS: Interaction with SARS-CoV-2 helicase, approved drugs, vapreotide (affinity: \u201312.88; S score: \u20139.84 kcal/mol), and atazanavir (affinity: \u201311.28; S score: \u20139.32 kcal/mol), approved drugs for treating AIDS-related diarrhoea and HIV infection, respectively, are observed with significantly low binding affinity and MOE score or binding free energy. The functional binding pockets of the clinically approved drugs on SARS-CoV-2 helicase protein molecule suggest that vapreotide and atazanavir may interrupt the activities of the SARS-CoV-2 helicase. CONCLUSIONS: The study suggests that vapreotide may be a choice of drug for wet lab studies to inhibit the infection of SARS-CoV-2.", "qid": 29, "docid": "2j56et4p", "rank": 40, "score": 22.192399978637695}, {"content": "Title: Perspectives for repurposing drugs for the coronavirus disease 2019 Content: The newly emerged 2019 novel coronavirus (CoV), named as severe acute respiratory syndrome CoV-2 (SARS-CoV-2), like SARS-CoV (now, SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV), has been associated with high infection rates with over 36,405 deaths. In the absence of approved marketed drugs against coronaviruses, the treatment and management of this novel CoV disease (COVID-19) worldwide is a challenge. Drug repurposing that has emerged as an effective drug discovery approach from earlier approved drugs could reduce the time and cost compared to de novo drug discovery. Direct virus-targeted antiviral agents target specific nucleic acid or proteins of the virus while host-based antivirals target either the host innate immune responses or the cellular machineries that are crucial for viral infection. Both the approaches necessarily interfere with viral pathogenesis. Here we summarize the present status of both virus-based and host-based drug repurposing perspectives for coronaviruses in general and the SARS-CoV-2 in particular.", "qid": 29, "docid": "hcj8fylw", "rank": 41, "score": 22.177600860595703}, {"content": "Title: RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery. Content: COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.", "qid": 29, "docid": "djhnd8kq", "rank": 42, "score": 22.077299118041992}, {"content": "Title: Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis Content: AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.", "qid": 29, "docid": "0sdjy80s", "rank": 43, "score": 22.043800354003906}, {"content": "Title: Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics Content: There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90 ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax ) at an approved dose in humans (Cmax /EC90 ratio). Only 14 of the 56 analyzed drugs achieved a Cmax /EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax /half-maximal effective concentration (EC50 ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.", "qid": 29, "docid": "r0zyfamz", "rank": 44, "score": 22.002399444580078}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "hg9i6v26", "rank": 45, "score": 21.997499465942383}, {"content": "Title: Prioritisation of Anti\u2010SARS\u2010Cov\u20102 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics Content: There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS\u2010CoV\u20102. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC(90) values recalculated from in vitro anti\u2010SARS\u2010CoV\u20102 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC(90) ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC(90) ratio above 1. A more in\u2010depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir\u2010boosted) and sulfadoxine achieved plasma concentrations above their reported anti\u2010SARS\u2010CoV\u20102 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (K(p)U(lung)) was also simulated to derive a lung Cmax/EC(50) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir\u2010boosted), tipranavir (ritonavir\u2010boosted), ivermectin, azithromycin and lopinavir (ritonavir\u2010boosted) were all predicted to achieve lung concentrations over 10\u2010fold higher than their reported EC(50). Nitazoxanide and sulfadoxine also exceeded their reported EC(50) by 7.8\u2010 and 1.5\u2010fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC(90) values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.", "qid": 29, "docid": "6nvi63rq", "rank": 46, "score": 21.949800491333008}, {"content": "Title: Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. Content: UNLABELLED The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. IMPORTANCE Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of \u223c10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.", "qid": 29, "docid": "w6bk2x1n", "rank": 47, "score": 21.86829948425293}, {"content": "Title: Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach Content: The pandemic prevalence of COVID-19 has become a very serious global health issue. Scientists all over the world have been heavily invested in the discovery of a drug to combat SARS-CoV-2. It has been found that RNA-dependent RNA Polymerase (RdRp) plays a crucial role in SARS-CoV-2 replication, and thus could be a potential drug target. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict an effective drug candidate targeting RdRp of SARS-CoV-2. This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5'-triphosphate-5'-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19. In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC 09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2; indicating their potentiality as effective inhibitors of the enzyme. Furthermore, ADME analysis along with analysis of toxicity was also investigated to check the pharmacokinetics and drug-likeness properties of the two compounds. Comparative structural analysis of protein-inhibitor complexes revealed that positions of the amino acid Y32, K47, Y122, Y129, H133, N138, D140, T141, S709 and N781 are crucial for drug surface hotspot in the RdRp of SARS-CoV-2.", "qid": 29, "docid": "8e50vgyi", "rank": 48, "score": 21.861299514770508}, {"content": "Title: Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs Content: Licence: CC BY-NC-ND 4 0 Citation information: Arya, Rimanshee;Das, Amit;Prashar, Vishal;Kumar, Mukesh (2020): Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs ChemRxiv Preprint https://doi org/10 26434/chemrxiv 11860011 v2 The cases of 2019 novel coronavirus (SARS-CoV-2) infection have been continuously increasing ever since its outbreak in China last December Currently, there are no approved drugs to treat the infection In this scenario, there is a need to utilize the existing repertoire of FDA approved drugs to treat the disease The rational selection of these drugs could be made by testing their ability to inhibit any SARS-CoV-2 proteins essential for viral life-cycle We chose one such crucial viral protein, the papain-like protease (PLpro), to screen the FDA approved drugs in silico The homology model of the protease was built based on the SARS-coronavirus PLpro structure, and the drugs were docked in S3/S4 pockets of the active site of the enzyme In our docking studies, sixteen FDA approved drugs, including chloroquine and formoterol, was found to bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus File list (1) download file view on ChemRxiv 2019-nCoV_final_draft2_ChemRxiv pdf (1 15 MiB) Abstract The cases of 2019 novel coronavirus (SARS-CoV-2) infection have been continuously increasing ever since its outbreak in China last December Currently, there are no approved drugs to treat the infection In this scenario, there is a need to utilize the existing repertoire of FDA approved drugs to treat the disease The rational selection of these drugs could be made by testing their ability to inhibit any SARS-CoV-2 proteins essential for viral life-cycle We chose one such crucial viral protein, the papain-like protease (PLpro), to screen the FDA approved drugs in silico The homology model of the protease was built based on the SARS-coronavirus PLpro structure, and the drugs were docked in S3/S4 pockets of the active site of the enzyme In our docking studies, sixteen FDA approved drugs, including chloroquine and formoterol, was found to bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus", "qid": 29, "docid": "n2tckfjq", "rank": 49, "score": 21.839099884033203}, {"content": "Title: iBioProVis: Interactive Visualization and Analysis of Compound Bioactivity Space. Content: SUMMARY iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs, and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2-D map, based on the similarity of structural properties of compounds and in the context of compounds' cognate targets. Similar compounds, which are embedded to proximate points on the 2-D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins' known ligands on the 2-D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on ACE2 protein which is SARS-CoV-2 Spike protein receptor. ACE2 binding compounds and 7 antiviral drugs were closely embedded in which two of them have been under clinical trial for COVID-19. AVAILABILITY AND IMPLEMENTATION iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.", "qid": 29, "docid": "5yc6u5t3", "rank": 50, "score": 21.73550033569336}, {"content": "Title: iBioProVis: Interactive Visualization and Analysis of Compound Bioactivity Space Content: SUMMARY: iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs, and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2-D map, based on the similarity of structural properties of compounds and in the context of compounds' cognate targets. Similar compounds, which are embedded to proximate points on the 2-D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins' known ligands on the 2-D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on ACE2 protein which is SARS-CoV-2 Spike protein receptor. ACE2 binding compounds and 7 antiviral drugs were closely embedded in which two of them have been under clinical trial for COVID-19. AVAILABILITY AND IMPLEMENTATION: iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "qid": 29, "docid": "jmiy97du", "rank": 51, "score": 21.735498428344727}, {"content": "Title: Genetically informed precision drug repurposing for lung function and implications for respiratory infection Content: Impaired lung function is associated with significant morbidity and mortality. Restrictive and obstructive lung disorders are a large contributor to decreased lung function, as well as the acute impact of infection. Measures of pulmonary function are heritable, and thus, we sought to utilise genomics to propose novel drug repurposing candidates which could improve respiratory outcomes. Lung function measures were found to be genetically correlated with metabolic and hormone traits which could be pharmacologically modulated, with a causal effect of increased fasting glucose on diminished lung function supported by latent causal variable models and Mendelian randomisation. We developed polygenic scores for lung function specifically within pathways with known drug targets to prioritise individuals who may benefit from particular drug repurposing opportunities, accompanied by transcriptome-wide association studies to identify drug-gene interactions with potential lung function increasing modes of action. These drug repurposing candidates were further considered relative to the host-viral interactome of three viruses with associated respiratory pathology (SARS-CoV2, influenza, and human adenovirus). We uncovered an enrichment amongst glycaemic pathways of human proteins which putatively interact with virally expressed SARS-CoV2 proteins, suggesting that antihyperglycaemic agents may have a positive effect both on lung function and SARS-CoV2 progression.", "qid": 29, "docid": "ruvz3f1c", "rank": 52, "score": 21.6200008392334}, {"content": "Title: CANDO and the infinite drug discovery frontier. Content: The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound-proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12-25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 'high value' predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.", "qid": 29, "docid": "wkkz4dry", "rank": 53, "score": 21.611000061035156}, {"content": "Title: SAveRUNNER: a network-based algorithm for drug repurposing and its application to COVID-19 Content: The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity, comorbidity, or for their association to drugs tentatively repurposed to treat COVID-19. Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments, as well as a new combination therapy of 5 drugs, actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies, and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.", "qid": 29, "docid": "jozd45ch", "rank": 54, "score": 21.510400772094727}, {"content": "Title: Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study Content: The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson-Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev. 2019, 119, 9478; Wang, Curr. Comput.-Aided Drug Des. 2006, 2, 287; Wang; ; Hou J. Chem. Inf. Model., 2012, 52, 1199). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.8 kcal/mol) is not nearly as low as that of the neutral form (-7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.9 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.", "qid": 29, "docid": "ttl1f9dd", "rank": 55, "score": 21.466800689697266}, {"content": "Title: Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study Content: [Image: see text] The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson\u2013Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev.2019, 119, 947831244000; Wang, Curr. Comput.-Aided Drug Des.2006, 2, 287; Wang; HouJ. Chem. Inf. Model., 2012, 52, 119922497310). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, \u221213.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (\u22123.8 kcal/mol) is not nearly as low as that of the neutral form (\u22127.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of \u221212.9 kcal/mol. Detailed receptor\u2013ligand interactions were analyzed and hot spots for the receptor\u2013ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.", "qid": 29, "docid": "upcsvjuo", "rank": 56, "score": 21.466798782348633}, {"content": "Title: Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase Content: The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2'-O-ribose methyltransferase (2'-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2'-O-MTase methylates the ribose 2'-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (&#916;G), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (&#916;G = -9.8 kcal/mol) & Raltegravir (&#916;G = -7.8 kcal/mol) for 3CLpro and Dolutegravir (&#916;G = -9.4 kcal/mol) and Bictegravir (&#916;G = -8.4 kcal/mol) for 2'-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "sd40c03b", "rank": 57, "score": 21.430299758911133}, {"content": "Title: Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2\u2032-O-ribose methyltransferase Content: The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2\u2032-O-ribose methyltransferase (2\u2032-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2\u2032-O-MTase methylates the ribose 2\u2032-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (\u0394G), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (\u0394G = \u22129.8 kcal/mol) & Raltegravir (\u0394G = \u22127.8 kcal/mol) for 3CLpro and Dolutegravir (\u0394G = \u22129.4 kcal/mol) and Bictegravir (\u0394G = \u22128.4 kcal/mol) for 2\u2032-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "tzsm1t44", "rank": 58, "score": 21.4302978515625}, {"content": "Title: Machine-Learning Driven Drug Repurposing for COVID-19 Content: The integration of machine learning methods into bioinformatics provides particular benefits in identifying how therapeutics effective in one context might have utility in an unknown clinical context or against a novel pathology. We aim to discover the underlying associations between viral proteins and antiviral therapeutics that are effective against them by employing neural network models. Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Model training excluded SARS-CoV-2 proteins and included only Phases II, III, IV and Approved level drugs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. Our results suggest multiple drug candidates, some of which complement recent findings from noteworthy clinical studies. Our in-silico approach to drug repurposing has promise in identifying new drug candidates and treatments for other viruses.", "qid": 29, "docid": "1nnqx1g9", "rank": 59, "score": 21.377399444580078}, {"content": "Title: SARS-CoV-2 E protein is a potential ion channel that can Be inhibited by Gliclazide and Memantine Content: COVID-19 is one of the most impactful pandemics in recorded history. As such, the identification of inhibitory drugs against its etiological agent, SARS-CoV-2, is of utmost importance, and in particular, repurposing may provide the fastest route to curb the disease. As the first step in this route, we sought to identify an attractive and viable target in the virus for pharmaceutical inhibition. Using three bacteria-based assays that were tested on known viroporins, we demonstrate that one of its essential components, the E protein, is a potential ion channel and, therefore, is an excellent drug target. Channel activity was demonstrated for E proteins in other coronaviruses, providing further emphasis on the importance of this functionally to the virus\u2019 pathogenicity. The results of a screening effort involving a repurposing drug library of ion channel blockers yielded two compounds that inhibit the E protein: Gliclazide and Memantine. In conclusion, as a route to curb viral virulence and abate COVID-19, we point to the E protein of SARS-CoV-2 as an attractive drug target and identify off-label compounds that inhibit it.", "qid": 29, "docid": "cjq0ep4f", "rank": 60, "score": 21.371000289916992}, {"content": "Title: Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review Content: Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.", "qid": 29, "docid": "a179xi5p", "rank": 61, "score": 21.346399307250977}, {"content": "Title: Revisiting potential druggable targets against SARS\u2010CoV\u20102 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review Content: Coronavirus disease\u201019 (COVID\u201019), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID\u201019 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS\u2010CoV\u20102. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target\u2010based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti\u2010SARS\u2010CoV\u20102 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS\u2010CoV\u20102 infection.", "qid": 29, "docid": "xkoilncd", "rank": 62, "score": 21.346397399902344}, {"content": "Title: Current status of COVID-19 therapies and drug repositioning applications Content: Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2.", "qid": 29, "docid": "1t4ykc01", "rank": 63, "score": 21.302600860595703}, {"content": "Title: Current Status of COVID-19 Therapies and Drug Repositioning Applications Content: The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.", "qid": 29, "docid": "q6bpic9m", "rank": 64, "score": 21.30259895324707}, {"content": "Title: Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication Content: Emergence of a highly contagious novel coronavirus, SARS-CoV-2 that causes COVID-19, has precipitated the current global health crisis with over 479,000 deaths and more than 9.3 million confirmed cases. Currently, our knowledge of the mechanisms of COVID-19 disease pathogenesis is very limited which has hampered attempts to develop targeted antiviral strategies. Therefore, we urgently need an effective therapy for this unmet medical need. Viruses hijack and dysregulate cellular machineries in order for them to replicate and infect more cells. Thus, identifying and targeting dysregulated signaling pathways that have been taken over by viruses is one strategy for developing an effective antiviral therapy. We have developed a high-throughput drug screening system to identify potential antiviral drugs targeting SARS-CoV-2. We utilized a small molecule library of 430 protein kinase inhibitors, which are in various stages of clinical trials. Most of the tested kinase antagonists are ATP competitive inhibitors, a class of nucleoside analogs, which have been shown to have potent antiviral activity. From the primary screen, we have identified 34 compounds capable of inhibiting viral cytopathic effect in epithelial cells. Network of drug and protein relations showed that these compounds specifically targeted a limited number of cellular kinases. More importantly, we have identified mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-Damage Response (DDR) pathways as key cellular signaling pathways critical for SARS-CoV-2 infection. Subsequently, a secondary screen confirmed compounds such as Berzosertib (VE-822), Vistusertib (AZD2014), and Nilotinib with anti SARS-CoV-2 activity. Finally, we found that Berzosertib, an ATR kinase inhibitor in the DDR pathway, demonstrated potent antiviral activity in a human epithelial cell line and human induced pluripotent stem cell (hIPSC)-derived cardiomyocytes. These inhibitors are already in clinical trials of phase 2 or 3 for cancer treatment, and can be repurposed as promising drug candidates for a host-directed therapy of SARS-CoV-2 infection. In conclusion, we have identified small molecule inhibitors exhibiting anti SARS-CoV-2 activity by blocking key cellular kinases, which gives insight on important mechanism of host-pathogen interaction. These compounds can be further evaluated for the treatment of COVID-19 patients following additional in vivo safety and efficacy studies. Disclosures None declared.", "qid": 29, "docid": "jz5wrhc4", "rank": 65, "score": 21.23259925842285}, {"content": "Title: Identification of Chymotrypsin-like Protease Inhibitors of SARS-CoV-2 Via Integrated Computational Approach. Content: Recently, the world has witnessed outbreak of a novel Coronavirus (SARS-CoV-2), the virus which initially emerged in Wuhan, China has now made its way to a large part of the world, resulting in a public emergency of international concern. The functional importance of Chymotrypsin-like protease (3CLpro) in viral replication and maturation turns it into an attractive target for the development of effective antiviral drugs against SARS and other coronaviruses. At present, there is no standard drug regime nor any vaccine available against the infection. The rapid development and identification of efficient interventions against SARS-CoV-2 remains a major challenge. Based on the available knowledge of closely related coronavirus and their safety profiles, repurposing of existing antiviral drugs and screening of available databases is considered a near term strategic and economic way to contain the SARS-CoV-2 pandemic. Herein, we applied computational drug design methods to identify Chymotrypsin-like protease inhibitors from FDA approved antiviral drugs and our in-house database of natural and drug-like compounds of synthetic origin. As a result three FDA approved drugs ( Remdesivir, Saquinavir and Darunavir) and two natural compounds (. flavone and coumarine derivatives) were identified as promising hits. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior, stability of protein-ligand contact, and binding affinity of the hit compounds. Our results indicate that the identified compounds can inhibit the function of Chymotrypsin-like protease (3CLpro) of Coronavirus. Considering the severity of the spread of coronavirus, the current study is in-line with the concept of finding the new inhibitors against the vital pathway of the corona virus to expedite the process of drug discovery.", "qid": 29, "docid": "m55mro2m", "rank": 66, "score": 21.181400299072266}, {"content": "Title: Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach Content: Recently, the world has witnessed outbreak of a novel Coronavirus (SARS-CoV-2), the virus which initially emerged in Wuhan, China has now made its way to a large part of the world, resulting in a public emergency of international concern. The functional importance of Chymotrypsin-like protease (3CLpro) in viral replication and maturation turns it into an attractive target for the development of effective antiviral drugs against SARS and other coronaviruses. At present, there is no standard drug regime nor any vaccine available against the infection. The rapid development and identification of efficient interventions against SARS-CoV-2 remains a major challenge. Based on the available knowledge of closely related coronavirus and their safety profiles, repurposing of existing antiviral drugs and screening of available databases is considered a near term strategic and economic way to contain the SARS-CoV-2 pandemic. Herein, we applied computational drug design methods to identify Chymotrypsin-like protease inhibitors from FDA approved antiviral drugs and our in-house database of natural and drug-like compounds of synthetic origin. As a result three FDA approved drugs (Remdesivir, Saquinavir and Darunavir) and two natural compounds (. flavone and coumarine derivatives) were identified as promising hits. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior, stability of protein-ligand contact, and binding affinity of the hit compounds. Our results indicate that the identified compounds can inhibit the function of Chymotrypsin-like protease (3CLpro) of Coronavirus. Considering the severity of the spread of coronavirus, the current study is in-line with the concept of finding the new inhibitors against the vital pathway of the corona virus to expedite the process of drug discovery.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "qato562y", "rank": 67, "score": 21.181398391723633}, {"content": "Title: COVID-19: Drug Targets and Potential Treatments Content: Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "qid": 29, "docid": "f6xhrpi8", "rank": 68, "score": 21.160999298095703}, {"content": "Title: Ca2+ Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity Content: Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca2+) play an important role in fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FPs share a high sequence homology, and here, we investigated whether Ca2+ is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate pseudoparticle (PP) infection of host cells in modulating Ca2+ environments. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV wild-type (WT) PP infection by approximately 2-fold and that E891 is a crucial residue for Ca2+ interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca2+ ratio, as opposed to an 1:2 SARS-CoV FP to Ca2+ ratio, suggesting significant differences in FP Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging infectious disease with zoonotic potential and has reservoirs in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans, with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data have found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This information can guide therapeutic solutions to block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks.", "qid": 29, "docid": "z086ewcs", "rank": 69, "score": 21.079599380493164}, {"content": "Title: Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach Content: The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.", "qid": 29, "docid": "eja8fkwv", "rank": 70, "score": 20.986000061035156}, {"content": "Title: COVID-19: Drug Targets and Potential Treatments Content: [Image: see text] Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "qid": 29, "docid": "2kfmgr7k", "rank": 71, "score": 20.984600067138672}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "aqge7xuu", "rank": 72, "score": 20.867799758911133}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "xui8cfzv", "rank": 73, "score": 20.8677978515625}, {"content": "Title: Causal Network Models of SARS-CoV-2 Expression and Aging to Identify Candidates for Drug Repurposing Content: Given the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug discovery platforms. We here take advantage of large-scale transcriptional drug screens combined with RNA-seq data of the lung epithelium with SARS-CoV-2 infection as well as the aging lung. To identify robust druggable protein targets, we propose a principled causal framework that makes use of multiple data modalities. Our analysis highlights the importance of serine/threonine and tyrosine kinases as potential targets that intersect the SARS-CoV-2 and aging pathways. By integrating transcriptomic, proteomic and structural data that is available for many diseases, our drug discovery platform is broadly applicable. Rigorous in vitro experiments as well as clinical trials are needed to validate the identified candidate drugs.", "qid": 29, "docid": "ofmjtri8", "rank": 74, "score": 20.85219955444336}, {"content": "Title: Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 Content: There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation.", "qid": 29, "docid": "hsc2x36j", "rank": 75, "score": 20.775999069213867}, {"content": "Title: Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics Content: Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 29, "docid": "nbc07tf7", "rank": 76, "score": 20.712900161743164}, {"content": "Title: Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics. Content: Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 29, "docid": "tw2nls29", "rank": 77, "score": 20.71289825439453}, {"content": "Title: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 Content: The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.", "qid": 29, "docid": "qebbkr6d", "rank": 78, "score": 20.7106990814209}, {"content": "Title: Insight Derived from Molecular Docking and Molecular Dynamics Simulations into the Binding Interactions Between HIV-1 Protease Inhibitors and SARS-CoV-2 3CLpro Content: A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was identified from respiratory illness patients in Wuhan, Hubei Province, China, which has recently emerged as a serious threat to the world public health Hower, no approved drugs have been found to effectively inhibit the virus Since it has been reported that the HIV-1 protease inhibitors can be used as anti-SARS drugs by tegarting SARS-CoV 3CLpro, we choose six approved anti-HIV-1 drugs to investigate their binding interactions between 3CLpro, and to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID19) caused by SARS-CoV-2 infection The molecular docking results indicate that, the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than its SARS homologue Two docking complexes (indinavir and darunavir) with high docking scores were futher subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two proteinase inhibitors and the 3CLpro Our results show that darunavir has the best binding affinity with SARS-CoV-2 and SARS-CoV 3CLpro among all inhibitors, indicating it has the potential to become an anti-COVID-19 clinical drug The likely reason behind the increased binding affinity of HIV-1 protease inhibitors toward SARS-CoV2 3CLpro than that of SARS-CoV were investigated by MD simulations Our study provides insight into the possible role of structural flexibility during interactions between 3CLpro and inhibitors, and sheds light on the structure-based design of anti-COVID-19 drugs targeting the SARS-CoV-2 3CLpro", "qid": 29, "docid": "m0hivi0u", "rank": 79, "score": 20.637699127197266}, {"content": "Title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data Content: With more than 3.8 million people infected Coronavirus Disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a critical threat to human health. There is no proven vaccine or specific drug to date, which highlights the urgent need for rapid development of therapeutics for COVID-19. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA approved drugs and pre-clinical small-molecule compounds by integrating the gene expression perturbation data by chemicals from the Library of Integrated Network-Based Cellular Signatures (LINCS) project with publically available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA approved drugs that have the potential to be effective against SARS-CoV-2 infection, 10 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. In conclusion, we have identified a list of repurposable anti-SARS- CoV-2 drugs using a systems biology approach.", "qid": 29, "docid": "7ftg6bfx", "rank": 80, "score": 20.579200744628906}, {"content": "Title: Stilbene-based natural compounds as promising drug candidates against COVID-19 Content: The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> -7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19. [Formula: see text] Communicated by Ramaswamy H. SarmaHighlightsStilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies.", "qid": 29, "docid": "unnrrnvr", "rank": 81, "score": 20.56089973449707}, {"content": "Title: Knowledge\u2010based structural models of SARS\u2010CoV\u20102 proteins and their complexes with potential drugs Content: The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID\u201019) caused by the novel coronavirus SARS\u2010CoV\u20102 a pandemic. There is, however, no confirmed anti\u2010COVID\u201019 therapeutic currently. In order to assist structure\u2010based discovery efforts for repurposing drugs against this disease, we constructed knowledge\u2010based models of SARS\u2010CoV\u20102 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID\u201019.", "qid": 29, "docid": "flkjekyo", "rank": 82, "score": 20.5132999420166}, {"content": "Title: Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs Content: The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 a pandemic. There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19.", "qid": 29, "docid": "onskc3u9", "rank": 83, "score": 20.51329803466797}, {"content": "Title: Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors Content: The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.", "qid": 29, "docid": "jnw0pnfu", "rank": 84, "score": 20.475500106811523}, {"content": "Title: In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication Content: A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library\u00ae composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20\u00b5M. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.", "qid": 29, "docid": "m7dwbheg", "rank": 85, "score": 20.44499969482422}, {"content": "Title: Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model Content: Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.", "qid": 29, "docid": "zb434ve3", "rank": 86, "score": 20.430200576782227}, {"content": "Title: GraphDTA: Predicting drug\u2013target binding affinity with graph neural networks Content: The development of new drugs is costly, time consuming, and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs. Computational models that estimate the interaction strength of new drug\u2013target pairs have the potential to expedite drug repurposing. Several models have been proposed for this task. However, these models represent the drugs as strings, which is not a natural way to represent molecules. We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug\u2013target affinity. We show that graph neural networks not only predict drug\u2013target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug\u2013target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. Availability of data and materials The proposed models are implemented in Python. Related data, pre-trained models, and source code are publicly available at https://github.com/thinng/GraphDTA. All scripts and data needed to reproduce the post-hoc statistical analysis are available from https://doi.org/10.5281/zenodo.3603523.", "qid": 29, "docid": "zult69f2", "rank": 87, "score": 20.375600814819336}, {"content": "Title: Computational modeling of Human-nCoV protein-protein interaction network Content: COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.", "qid": 29, "docid": "k4f79dr4", "rank": 88, "score": 20.372900009155273}, {"content": "Title: Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19. Content: The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.", "qid": 29, "docid": "62iqyk0r", "rank": 89, "score": 20.36590003967285}, {"content": "Title: Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19 Content: The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.", "qid": 29, "docid": "qmmy8amo", "rank": 90, "score": 20.36589813232422}, {"content": "Title: Corona virus versus existence of human on the earth: A computational and biophysical approach Content: SARS-CoV-2 has a positive sense RNA genome of 29.9 kb in size, showing high sequence similarity to the BAT-CoV, SARS-CoV, MERS-CoV. SARS-CoV-2 is composed of 14 open reading frames (ORFs), which encodes for a total of 27 proteins divided into structural and non-structural proteins (NSPs). The fundamental structural protein-encoding genes are a spike protein (S) gene, envelope protein (E) gene, a membrane protein (M) gene, and a nucleocapsid protein (N) gene. They make about 33% of the entire genome and are vital for the viral life cycle. Rest 67% is distributed among different NSPs (such as Mpro, helicase, and RNA-dependent RNA polymerase) encoding genes across the ORFs, which are involved in virus-cell receptor interactions during viral entry. Researchers are trying to formulate vaccines, therapeutic antibodies or protein-targeted antiviral drugs to control the spread. This review proceeds stepwise through the COVID-19 outbreak, structural and genomic organization, entry mechanism, pathogenesis, and finally highlighting the essential proteins involved at each step that might be potential targets for drug discovery. Currently, approved treatment modalities consist of only supportive care and oxygen supplementation. This review is established on the current knowledge that has expanded on structural motifs and topology of proteins and their functions.", "qid": 29, "docid": "9qneslip", "rank": 91, "score": 20.32670021057129}, {"content": "Title: Corona virus versus existence of human on the earth: A computational and biophysical approach Content: SARS-CoV-2 has a positive sense RNA genome of 29.9 kb in size, showing high sequence similarity to the BAT-CoV, SARS-CoV, MERS-CoV. SARS-CoV-2 is composed of 14 open reading frames (ORFs), which encodes for a total of 27 proteins divided into structural and non-structural proteins (NSPs). The fundamental structural protein-encoding genes are a spike protein (S) gene, envelope protein (E) gene, a membrane protein (M) gene, and a nucleocapsid protein (N) gene. They make about 33% of the entire genome and are vital for the viral life cycle. Rest 67% is distributed among different NSPs (such as M(pro), helicase, and RNA-dependent RNA polymerase) encoding genes across the ORFs, which are involved in virus-cell receptor interactions during viral entry. Researchers are trying to formulate vaccines, therapeutic antibodies or protein-targeted antiviral drugs to control the spread. This review proceeds stepwise through the COVID-19 outbreak, structural and genomic organization, entry mechanism, pathogenesis, and finally highlighting the essential proteins involved at each step that might be potential targets for drug discovery. Currently, approved treatment modalities consist of only supportive care and oxygen supplementation. This review is established on the current knowledge that has expanded on structural motifs and topology of proteins and their functions.", "qid": 29, "docid": "ccau1qwc", "rank": 92, "score": 20.326698303222656}, {"content": "Title: Hijacking SARS-Cov-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on receptor binding region Content: The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In the light of the urgent need to identify novel approaches to be used in the emergency phase, a largely explored strategy has been the repurpose of clinically available drugs as new antivirals, by targeting different viral proteins. In this paper, we describe a drug repurposing strategy based on a virtual screening of druggable pockets located in the central \u03b2-sheet core of the SARS-CoV-2 Spike protein RBD supported by in vitro tests identifying several steroidal derivatives as SARS-CoV-2 entry inhibitors. Our results demonstrate that several potential binding sites exist in the SARS CoV-2 S protein, and that the occupancy of these pockets reduces the ability of the S protein RBD to bind to the ACE2 consensus in vitro. In particular, natural occurring and clinically available steroids as glycyrrhetinic and oleanolic acids, as well as the bile acids derivatives glyco-UDCA and obeticholic acid have been shown to be effective in preventing virus entry in the case of low viral load. All together, these results might help to define novel approaches to reduce the viral load by using SARS-CoV-2 entry inhibitors.", "qid": 29, "docid": "l41lq2sc", "rank": 93, "score": 20.302900314331055}, {"content": "Title: The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States Content: Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins\u2014whose aberrant activities govern the reprogramed state of coronavirus-infected cells\u2014presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to established treatments. Specifically, we propose that a small module of host cell Master Regulator proteins (ViroCheckpoint) is hijacked by the virus to support its efficient replication and release. Conventional methodologies are not well suited to elucidate these potentially targetable proteins. By using the VIPER network-based algorithm, we successfully interrogated 12h, 24h, and 48h signatures from Calu-3 lung adenocarcinoma cells infected with SARS-CoV, to elucidate the time-dependent reprogramming of host cells and associated Master Regulator proteins. We used the NYS CLIA-certified Darwin OncoTreat algorithm, with an existing database of RNASeq profiles following cell perturbation with 133 FDA-approved and 195 late-stage experimental compounds, to identify drugs capable of virtually abrogating the virus-induced Master Regulator signature. This approach to drug prioritization and repurposing can be trivially extended to other viral pathogens, including SARS-CoV-2, as soon as the relevant infection signature becomes available.", "qid": 29, "docid": "viwr6djt", "rank": 94, "score": 20.279699325561523}, {"content": "Title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin Content: The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "bha6pl7o", "rank": 95, "score": 20.18269920349121}, {"content": "Title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin Content: The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "dq2empne", "rank": 96, "score": 20.182697296142578}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.", "qid": 29, "docid": "7h3rrea7", "rank": 97, "score": 20.177499771118164}, {"content": "Title: Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19 Content: The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly translated to clinical care. Unfortunately, traditional drug discovery methods have a >90% failure rate and can take 10\u201315 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious single agents and combination therapies against SARS-CoV-2. Quantitative high-content morphological profiling was coupled with an AI-based machine learning strategy to classify features of cells for infection and stress. This assay detected multiple antiviral mechanisms of action (MOA), including inhibition of viral entry, propagation, and modulation of host cellular responses. From a library of 1,425 FDA-approved compounds and clinical candidates, we identified 16 dose-responsive compounds with antiviral effects. In particular, we discovered that lactoferrin is an effective inhibitor of SARS-CoV-2 infection with an IC(50) of 308 nM and that it potentiates the efficacy of both remdesivir and hydroxychloroquine. Lactoferrin also stimulates an antiviral host cell response and retains inhibitory activity in iPSC-derived alveolar epithelial cells, a model for the primary site of infection. Given its safety profile in humans, these data suggest that lactoferrin is a readily translatable therapeutic adjunct for COVID-19. Additionally, several commonly prescribed drugs were found to exacerbate viral infection and warrant clinical investigation. We conclude that morphological profiling for drug repurposing is an effective strategy for the selection and optimization of drugs and drug combinations as viable therapeutic options for COVID-19 pandemic and other emerging infectious diseases.", "qid": 29, "docid": "ort27p77", "rank": 98, "score": 20.137699127197266}, {"content": "Title: Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach. Content: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.", "qid": 29, "docid": "9bhp3lph", "rank": 99, "score": 20.113300323486328}, {"content": "Title: Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach Content: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "cvavb7j1", "rank": 100, "score": 20.113298416137695}]}
{"query": "is remdesivir an effective treatment for COVID-19", "hits": [{"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 30, "docid": "1cph1uij", "rank": 1, "score": 9.640999794006348}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 30, "docid": "jxbch44o", "rank": 2, "score": 9.640998840332031}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Background Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.", "qid": 30, "docid": "p6uliadr", "rank": 3, "score": 9.163800239562988}, {"content": "Title: Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment Content: Background: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing understanding of the benefit-risk balance for remdesivir in COVID-19 treatment by using a structured method which uses all available data. Methods: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared to standard of care, placebo or other treatments. We searched PubMed,Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several key benefits and risks for use of remdesivir in COVID-19 compared to placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR=1.23, 95% CI: 0.87, 1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) comparted to the placebo group (26%), however more patients in the remdesivir group discontinued treatment as a result of an adverse event compared to those patients receiving placebo (12% vs 5%). Conclusions: Preliminary clinical trial results suggest a favourable benefit-risk profile for remdesivir compared to placebo, however there is limited safety data available at the current time. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 30, "docid": "dieaqxmi", "rank": 4, "score": 9.06089973449707}, {"content": "Title: Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis Content: Background: We evaluated the efficacy and safety of remdesivir for the treatment of COVID-19. Methods: Systematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed. Results: Two placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs. Interpretation: There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.", "qid": 30, "docid": "4vfk99f5", "rank": 5, "score": 9.04069995880127}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \"Remdesivir\" or 'GS-5734\u00e2\u0080\u00b3 AND \"COVID-19\" or \"SARS-CoV-2\" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 30, "docid": "1eiw7bxh", "rank": 6, "score": 9.003899574279785}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \u201cRemdesivir\u201d or \u2018GS-5734\u2033 AND \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 30, "docid": "gqqdx2r5", "rank": 7, "score": 9.003898620605469}, {"content": "Title: Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment Content: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. METHODS: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 30, "docid": "gxogowwb", "rank": 8, "score": 8.998700141906738}, {"content": "Title: Remdesivir in Treatment of COVID-19: A Systematic Benefit\u2013Risk Assessment Content: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit\u2013risk assessment was designed and conducted to examine the benefit\u2013risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit\u2013risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit\u2013risk evaluation as more data become available. METHODS: The Benefit\u2013Risk Action Team (BRAT) framework was used to assess the overall benefit\u2013risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87\u20131.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit\u2013risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit\u2013risk assessment.", "qid": 30, "docid": "xrvynfr6", "rank": 9, "score": 8.998699188232422}, {"content": "Title: Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More Content: Abstract COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as \u2018molecule of hope\u2019 for the treatment of this disease. USFDA approve this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "qid": 30, "docid": "2lwzhqer", "rank": 10, "score": 8.995200157165527}, {"content": "Title: A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir. Content: Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "qid": 30, "docid": "bz1lz2ze", "rank": 11, "score": 8.981300354003906}, {"content": "Title: A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir Content: Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "qid": 30, "docid": "ygbfvjz8", "rank": 12, "score": 8.98129940032959}, {"content": "Title: Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More Content: COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "qid": 30, "docid": "8n6eybze", "rank": 13, "score": 8.966500282287598}, {"content": "Title: Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials Content: BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER This study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).", "qid": 30, "docid": "qxsr3uii", "rank": 14, "score": 8.91469955444336}, {"content": "Title: Remdesivir Efficacy in Coronavirus Disease 2019 (COVID-19): A Systematic Review Content: Background: Researchers are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the treatment efficacy and safety of Remdesivir in hospitalized patients with COVID-19. Methods: We performed a systematic search of the Pubmed, Embase, Web of Science, Google scholar, and MedRxiv for relevant observational and interventional studies. Measured outcomes were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: 3 RCTs and 2 cohorts were included in our study. In 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day treatment of Remdesivir efficacy versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that Remdesivir efficacy was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowers 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have significant difference; however, severe adverse event rate was lower in 5-day Remdesivir group compared to 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.", "qid": 30, "docid": "6tcwu832", "rank": 15, "score": 8.90530014038086}, {"content": "Title: Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials Content: Background: In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19. Method and analysis: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo. Ethics and dissemination: This study does not require ethical approval, because no participants data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal. Registration: This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript. Keywords: 2019 novel coronavirus, 2019-nCoV, Coronavirus diseases 2019, COVID-19, SARS-cov-2, Remdesivir, Randomized Controlled Trials. Systematic review, Meta-analysis, protocol", "qid": 30, "docid": "aosmo568", "rank": 16, "score": 8.893099784851074}, {"content": "Title: Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment Content: [Image: see text] While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.", "qid": 30, "docid": "kq77whdx", "rank": 17, "score": 8.831600189208984}, {"content": "Title: The journey of remdesivir: from Ebola to COVID-19 Content: Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.", "qid": 30, "docid": "aivub6mi", "rank": 18, "score": 8.820699691772461}, {"content": "Title: Impacts of remdesivir on dynamics and efficacy stratified by the severity of COVID-19: a simulated two-arm controlled study Content: Background: The impact of remdesivir on length of stay of hospitalization, high-risk state, and death stratified by the severity of COVID-19 at enrollment is controversial. Methods: We applied a simulated two-arm controlled study design to the data on compassionate use of remdesivir as a secondary analysis. Dynamics of risk states and death from COVID-19 patients defined by the six-point disease severity recommended by the WHO R&D and the time to discharge from hospital were used to evaluate the efficacy of remdesivir treatment compared with standard care. Results: Stratified by the risk state at enrollment, low-risk patients exhibited the highest efficacy of remdesivir in reducing subsequent progression to high-risk state by 67% (relative risk (RR)=0.33,95% CI: 0.30-0.35) and further to death by 55% (RR=0.45, 95%CI: 0.39-0.50). For the medium-risk patients, less but still statistically significant efficacy results were noted in reducing progression to high-risk state by 52% (RR=0.48, 95% CI: 0.45-0.51) and further to death by 40% (RR=0.60, 95% CI:0.54-0.66). High-risk state patients treated with remdesivir led to a 25% statistically significant reduction in death (RR=0.75, 95% CI: 0.69-0.82). Regarding the outcome of discharge, remdesivir treatment was most effective for medium-risk patients at enrollment (RR: 1.41, 95% CI: 1.35-1.47) followed by high- (RR=1.34, 95% CI: 1.27-1.42) and low-risk patients (RR=1.28, 95% CI: 1.25-1.31). Conclusion: Our results with a simulated two-arm controlled study have provided a new insight into the precision treatment of remdesivir for COVID-19 patients based on risk-stratified efficacy.", "qid": 30, "docid": "4od9gu6y", "rank": 19, "score": 8.765299797058105}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5\u20139 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]", "qid": 30, "docid": "4178ui2c", "rank": 20, "score": 8.657400131225586}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.", "qid": 30, "docid": "r0znh1bi", "rank": 21, "score": 8.65739917755127}, {"content": "Title: Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis Content: Background Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use. Methods A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study. Results Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days ), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96). Conclusion In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.", "qid": 30, "docid": "7xc47la7", "rank": 22, "score": 8.621000289916992}, {"content": "Title: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Content: BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged &#8805;18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1\u00b723 [95% CI 0\u00b787-1\u00b775]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1\u00b752 [0\u00b795-2\u00b743]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "qid": 30, "docid": "c74zdtnn", "rank": 23, "score": 8.522600173950195}, {"content": "Title: Delayed Initiation of Remdesivir in a COVID-19-Positive Patient Content: We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40-year-old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID-19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID-19 polymerase chain reaction result. Supportive measures, in addition to a 5-day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS-CoV-2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS-CoV-2 as well as to meet manufacturing demands.", "qid": 30, "docid": "jql4n0td", "rank": 24, "score": 8.501799583435059}, {"content": "Title: Delayed Initiation of Remdesivir in a COVID\u201019\u2010Positive Patient Content: We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40\u2010year\u2010old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID\u201019) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID\u201019 polymerase chain reaction result. Supportive measures, in addition to a 5\u2010day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS\u2010CoV\u20102, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS\u2010CoV\u20102 as well as to meet manufacturing demands.", "qid": 30, "docid": "ssuao9mb", "rank": 25, "score": 8.501798629760742}, {"content": "Title: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Content: Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged \u226518 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2\u201310 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir\u2013ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1\u00b723 [95% CI 0\u00b787\u20131\u00b775]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1\u00b752 [0\u00b795\u20132\u00b743]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "qid": 30, "docid": "bzeqs5oh", "rank": 26, "score": 8.40530014038086}, {"content": "Title: Early experience with remdesivir in SARS-CoV-2 pneumonia Content: At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.", "qid": 30, "docid": "mp3qb33p", "rank": 27, "score": 8.355600357055664}, {"content": "Title: Role of 1\u2019-Ribose Cyano Substitution for Remdesivir to Effectively Inhibit both Nucleotide Addition and Proofreading in SARS-CoV-2 Viral RNA Replication Content: COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) provides a promising but challenging drug target due to its intrinsic proofreading exoribonuclease (ExoN) function. Nucleoside triphosphate (NTP) analogues added to the growing RNA chain should supposedly terminate viral RNA replication, but ExoN can cleave the incorporated compounds and counteract their efficacy. Remdesivir targeting SARS-CoV-2 RdRp exerts high drug efficacy in vitro and in vivo. However, its underlying inhibitory mechanisms remain elusive. Here, we performed all-atom molecular dynamics (MD) simulations with an accumulated simulation time of 12.6 microseconds to elucidate the molecular mechanisms underlying the inhibitory effects of remdesivir in nucleotide addition (RdRp complex: nsp12-nsp7-nsp8) and proofreading (ExoN complex: nsp14-nsp10). We found that the 1\u2019-cyano group of remdesivir possesses the dual role of inhibiting both nucleotide addition and proofreading. For nucleotide addition, we showed that incorporation of one remdesivir is not sufficient to terminate RNA synthesis. Instead, the presence of the polar 1\u2019-cyano group of remdesivir at an upstream site causes instability via its electrostatic interactions with a salt bridge formed by Asp865 and Lys593, rendering translocation unfavourable. This may eventually lead to a delayed chain termination of RNA extension by three nucleotides. For proofreading, remdesivir can inhibit cleavage via the steric clash between the 1\u2019-cyano group and Asn104. To further examine the role of 1\u2019-cyano group in remdesivir\u2019s inhibitory effects, we studied three additional NTP analogues with other types of modifications: favipiravir, vidarabine, and fludarabine. Our simulations suggest that all three of them are prone to ExoN cleavage. Our computational findings were further supported by an in vitro assay in Vero E6 cells using live SARS-CoV-2. The dose-response curves suggest that among tested NTP analogues, only remdesivir exerts significant inhibitory effects on viral replication. Our work provides plausible mechanisms at molecular level on how remdesivir inhibits viral RNA replication, and our findings may guide rational design for new treatments of COVID-19 targeting viral replication.", "qid": 30, "docid": "o1ff4hex", "rank": 28, "score": 8.318599700927734}, {"content": "Title: Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19 Content: [Image: see text] The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action\u2014to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir\u2019s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.", "qid": 30, "docid": "zdfx3zo3", "rank": 29, "score": 8.304300308227539}, {"content": "Title: Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV-2 RNA-Dependent RNA Polymerase Content: [Image: see text] Starting from late 2019, the coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures, and supporting apparatuses. Recently, because of its positive results in clinical trials, remdesivir was approved by the Food and Drug Administration to treat COVID-19 through Emergency Use Authorization. Here, we used molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). We first constructed the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identity of 95.8%). We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template. The putative binding structure was further optimized with molecular dynamics simulations. The resulting stable preinsertion state of remdesivir appeared to form hydrogen bonds with the RNA template when aligned with the newly solved cryo-EM structure of SARS-CoV-2 RdRp. The relative binding free energy between remdesivir and ATP was calculated to be \u22122.80 \u00b1 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP. The \u223c100-fold improvement in the K(d) from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site. Key residues D618, S549, and R555 are found to be the contributors to the binding affinity of remdesivir. These findings suggest that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA replication, with key residues also identified for future lead optimization and/or drug resistance studies.", "qid": 30, "docid": "13l2cbg1", "rank": 30, "score": 8.300999641418457}, {"content": "Title: Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV-2 RNA-Dependent RNA Polymerase Content: Starting from late 2019, the coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures, and supporting apparatuses. Recently, because of its positive results in clinical trials, remdesivir was approved by the Food and Drug Administration to treat COVID-19 through Emergency Use Authorization. Here, we used molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). We first constructed the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identity of 95.8%). We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template. The putative binding structure was further optimized with molecular dynamics simulations. The resulting stable preinsertion state of remdesivir appeared to form hydrogen bonds with the RNA template when aligned with the newly solved cryo-EM structure of SARS-CoV-2 RdRp. The relative binding free energy between remdesivir and ATP was calculated to be -2.80 \u00b1 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP. The \u00e2\u0088\u00bc100-fold improvement in the Kd from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site. Key residues D618, S549, and R555 are found to be the contributors to the binding affinity of remdesivir. These findings suggest that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA replication, with key residues also identified for future lead optimization and/or drug resistance studies.", "qid": 30, "docid": "yjar2ctw", "rank": 31, "score": 8.30099868774414}, {"content": "Title: Current Evidence of the Pharmacological Treatments for Novel Coronavirus Disease 2019 (COVID-19) A Scoping Review Content: Background: As of May 2 2020, 3,267,184 confirmed cases of COVID-19 and 229,971 COVID-19-caused deaths have been reported worldwide. Currently, there is limited clarity on the pharmacological treatments available for the novel coronavirus. We systematically identified the current evidence and ongoing research on the pharmacological treatments for COVID-19. Methods: We conducted a scoping review using PRISMA-ScR. Observational studies, including cohort studies and case series, as well as experimental studies, including randomized controlled trials (RCTs) and non-RCTs were searched electronically on April 7, 2020 and by hand on May 1, 2020. PubMed, EMBASE, and Cochrane library databases were searched along with seven trial registries. The inclusion criteria were patients with confirmed COVID-19 who received pharmacological therapies, including hydroxychloroquine and chloroquine, lopinavir/ritonavir, remdesivir, tocilizumab, and favipiravir. Results: We identified 222 studies on pharmacological treatment of the novel coronavirus. We included 11 of these studies in this review, including the ones on hydroxychloroquine and chloroquine (one cohort), lopinavir/ritonavir (one RCT, three cohorts, and two case series), remdesivir (one RCT and one case series), tocilizumab (one case series), and favipiravir (one RCT). In the three RCTs carried out in China, both lopinavir/ritonavir and remdesivir did not show any significant earlier clinical improvement in case of severe infection [Hazard ratio (HR): 1.31, p=0.09 and HR: 1.24, p=0.24, respectively], The clinical recovery rate on day seven was not significantly different between the favipiravir and arbidol groups (p=0.14) for moderate patients, although the duration of pyrexia and cough in the favipiravir group was significantly shorter as compared to the arbidol group (p<0.01). There are 135 ongoing RCTs, including 72 for hydroxychloroquine and chloroquine, 29 for lopinavir/ritonavir, 14 for remdesivir, 16 for tocilizumab, and 4 for favipiravir. Conclusion: The clinical effectiveness and safety of these drugs for the treatment of COVID-19 remains unclear owing to the lack of large, high-quality RCTs. However, in the event of emerging infectious diseases, we need to repeatedly and systematically update the best available evidence to avoid misleading information.", "qid": 30, "docid": "txvx5fy5", "rank": 32, "score": 8.277799606323242}, {"content": "Title: Case reports study of the first five patients COVID-19 treated with remdesivir in France Content: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "qid": 30, "docid": "m69ceq2t", "rank": 33, "score": 8.242400169372559}, {"content": "Title: Case reports study of the first five patients COVID-19 treated with remdesivir in France Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "qid": 30, "docid": "oc0m6r5c", "rank": 34, "score": 8.242399215698242}, {"content": "Title: Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE: A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION: Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.", "qid": 30, "docid": "d4tc2xe7", "rank": 35, "score": 8.226400375366211}, {"content": "Title: Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19). Content: BACKGROUND There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.", "qid": 30, "docid": "tdfqhty8", "rank": 36, "score": 8.226399421691895}, {"content": "Title: Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review Content: The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "qid": 30, "docid": "fy8tyj9a", "rank": 37, "score": 8.178600311279297}, {"content": "Title: Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review. Content: The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "qid": 30, "docid": "inibtytf", "rank": 38, "score": 8.17859935760498}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. Content: Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 30, "docid": "8cvjsisw", "rank": 39, "score": 8.174599647521973}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review Content: Importance: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 30, "docid": "yth9hh5q", "rank": 40, "score": 8.174598693847656}, {"content": "Title: A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease Content: BACKGROUND: The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. METHOD: Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. RESULTS: Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. CONCLUSION: Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19.", "qid": 30, "docid": "phxu6usy", "rank": 41, "score": 8.164999961853027}, {"content": "Title: Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019 Content: Importance: Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective: To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants: Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions: Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours \u00d7 2 doses followed by 200 mg every 12 hours \u00d7 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures: The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results: For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng \u00d7 h/mL) were similar to adults (4398 ng \u00d7 h/mL). Conclusions and Relevance: This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.", "qid": 30, "docid": "13n2ks4l", "rank": 42, "score": 8.11460018157959}, {"content": "Title: Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019. Content: Importance Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours \u00d7 2 doses followed by 200 mg every 12 hours \u00d7 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng \u00d7 h/mL) were similar to adults (4398 ng \u00d7 h/mL). Conclusions and Relevance This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.", "qid": 30, "docid": "v6t9n2wh", "rank": 43, "score": 8.114599227905273}, {"content": "Title: Emerging Treatment and Prevention Strategies against COVID-19: A Brief Update Content: Patients with novel coronavirus disease 2019 (COVID-19) are at significantly increased risk for mortality and morbidity. Current management remains supportive care, ranging from symptomatic outpatient management to full\u2013intensive care support, including intravenous fluids, invasive, and non-invasive oxygen supplementation. In patients with septic shock, treatment with antibiotics and vasopressors are recommended to keep mean arterial pressure (MAP) \u2265 65 mm Hg and lactate < 2 mmol/L. Because of the lack of effectiveness and possible adverse effects, routine corticosteroids should be avoided unless they are indicated for another reason (exacerbation of asthma or chronic obstructive pulmonary disease [COPD], and septic shock in whom fluids and vasopressors do not restore hemodynamic stability). There is currently no sufficient evidence of efficacy of hydroxychloroquine/chloroquine, remdesivir, and other antivirals in the treatment or prevention of COVID-19. Limited evidence shows that COVID-19 convalescent plasma can be used as a treatment of COVID-19 without the occurrence of severe adverse events. Drug regulatory agencies granted an emergency-use authorization of chloroquine/hydroxychloroquine and remdesivir to treat patients when a clinical trial is not available or participation is not feasible. Chloroquine and hydroxychloroquine are associated with QT interval prolongation and life-threatening cardiac arrhythmia in patients with pre-existing cardiovascular disease. Guidelines are issued for use of convalescent plasma in patients with serious or immediately life-threatening COVID-19. Data from several ongoing randomized controlled trials will provide further evidence regarding the safety and efficacy of these drugs for the treatment of COVID-19.", "qid": 30, "docid": "6bdzut3d", "rank": 44, "score": 8.114399909973145}, {"content": "Title: A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease Content: Abstract Background The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. Method Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. Results Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. Conclusion Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19.", "qid": 30, "docid": "pgxew3yk", "rank": 45, "score": 8.107799530029297}, {"content": "Title: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses Content: Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734\u2122) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524\u2122), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.", "qid": 30, "docid": "95fc828i", "rank": 46, "score": 8.103799819946289}, {"content": "Title: Efficacy of remdesivir in patients with COVID-19: a protocol for systematic review and meta-analysis of randomised controlled trials Content: BACKGROUND: Despite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19. METHOD AND ANALYSIS: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care. ETHICS AND DISSEMINATION: There are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences. PROSPERO REGISTRATION NUMBER: CRD42020177953.", "qid": 30, "docid": "kcrmi3x8", "rank": 47, "score": 8.086799621582031}, {"content": "Title: COVID-19: The Potential Role of Copper and N-acetylcysteine (NAC) in a Combination of Candidate Antiviral Treatments Against SARS-CoV-2 Content: BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS: The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS: Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION: The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.", "qid": 30, "docid": "s7p88fzw", "rank": 48, "score": 8.054300308227539}, {"content": "Title: COVID-19: The Potential Role of Copper and N-acetylcysteine (NAC) in a Combination of Candidate Antiviral Treatments Against SARS-CoV-2. Content: BACKGROUND On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.", "qid": 30, "docid": "va9ihthm", "rank": 49, "score": 8.054299354553223}, {"content": "Title: Remdesivir data offer hope, with caveats Content: Gilead Sciences\u2019 experimental antiviral remdesivir helped people with COVID-19 recover faster, according to limited data released on April 29 from a trial led by the US National Institute of Allergy and Infectious Diseases The Food and Drug Administration is expected in the coming days to take the unprecedented step of issuing an emergency use authorization, which will make the drug more readily available for stockpiling The study by NIAID, which is part of the National Institutes of Health, is considered to be the highest quality among the myriad Phase III trials testing remdesivir\u2019s effectiveness against COVID-19, the disease caused by the novel coronavirus Unlike most other trials, it includes a placebo arm, a part of a trial\u2019s design that scientists rely on for a clear signal of a treatment\u2019s worth The trial enrolled 1,063 people, 20% of whom received the standard of care rather than remdesivir The primary end point View: PDF ;Full Text HTML", "qid": 30, "docid": "7bpdhcdp", "rank": 50, "score": 8.017999649047852}, {"content": "Title: Scaling up remdesivir amid the coronavirus crisis Content: With society clamoring for something\u2014anything\u2014that can stem the rapidly rising death toll of the COVID-19 pandemic, Gilead Sciences\u2019 antiviral remdesivir has emerged as a closely watched treatment option Laboratory studies of other coronaviruses suggested the drug might be able to take down this new one, which causes COVID-19 As the outbreak took hold in China in January, it was among the first treatments that doctors tried Now, with cases worldwide at more than 3 million, scrutiny of data coming out of clinical trials of the drug has reached fever pitch When the health-focused news site Stat posted a story based on a leaked video of a University of Chicago clinician talking optimistically about remdesivir\u2019s possible effectiveness, it didn\u2019t just prop up Gilead\u2019s stock price;it lifted the entire stock market With each new anecdote, whether about an individual patient or a hunch from a doctor running a trial, the pressure View: PDF ;Full Text HTML", "qid": 30, "docid": "nez8la3d", "rank": 51, "score": 7.999199867248535}, {"content": "Title: Remdesivir for the Treatment of Covid-19 - Preliminary Report Content: BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.).", "qid": 30, "docid": "tn2xfmry", "rank": 52, "score": 7.909800052642822}, {"content": "Title: Remdesivir for the Treatment of Covid-19 \u2014 Preliminary Report Content: BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)", "qid": 30, "docid": "uohbxoeb", "rank": 53, "score": 7.909799098968506}, {"content": "Title: Statistical Issues and Lessons Learned from COVID-19 Clinical Trials with Lopinavir-Ritonavir and Remdesivir Content: BACKGROUND: Recently, three randomized clinical trials on COVID-19 treatments were completed, one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: From statistical perspectives, we identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al. failed to reach the planned sample size due to a lack of eligible patients, while the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al. reported the median recovery time of the remdesivir and placebo groups and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI [-3.62, 0.28]; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al., the difference of RMTIs at day 28 was -0.89 day (95% CI [-2.84, 1.06]; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the HR estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al., the difference of RMTRs between the remdesivir and placebo groups at day 30 was -2.7 days (95% CI [-4.0, -1.2]; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI [-3, 0]; P=.65) was insignificant, while the differences manifested to be statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis for ongoing and future COVID-19 trials.", "qid": 30, "docid": "6jo4308s", "rank": 54, "score": 7.887499809265137}, {"content": "Title: Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir Content: BACKGROUND: Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was \u20131.67 days (95% CI \u20133.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was \u20130.89 days (95% CI \u20132.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was \u20132.7 days (95% CI \u20134.0 to \u20131.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI \u20133 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials.", "qid": 30, "docid": "bcb78jkp", "rank": 55, "score": 7.88749885559082}, {"content": "Title: Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial Content: BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (&#8805; 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.", "qid": 30, "docid": "lhzcm4bt", "rank": 56, "score": 7.870299816131592}, {"content": "Title: Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial Content: BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30(th) January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (\u2265 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6(th) February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.", "qid": 30, "docid": "mur7txck", "rank": 57, "score": 7.870298862457275}, {"content": "Title: Current pharmacological treatments for SARS-COV-2: A narrative review Content: The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.", "qid": 30, "docid": "303b23dd", "rank": 58, "score": 7.867400169372559}, {"content": "Title: Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary Content: The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases. Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base. The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge. Communicated by Ramaswamy H. Sarma", "qid": 30, "docid": "np6nfvf2", "rank": 59, "score": 7.849999904632568}, {"content": "Title: In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2 Content: In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 \u03bcM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.", "qid": 30, "docid": "vzyrcmu4", "rank": 60, "score": 7.832200050354004}, {"content": "Title: Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease Content: BACKGROUND: Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. OBJECTIVES: The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. METHODS: Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 \u03bcm, 2.1 \u00d7 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. RESULTS: Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. CONCLUSIONS: This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.", "qid": 30, "docid": "bpou9p89", "rank": 61, "score": 7.814300060272217}, {"content": "Title: Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease Content: BACKGROUND: Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. OBJECTIVES: The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. METHODS: Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 \u00b5m, 2.1\u00e2\u0081\u009f\u00d7\u00e2\u0081\u009f50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. RESULTS: Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. CONCLUSIONS: This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.", "qid": 30, "docid": "w3iis2sd", "rank": 62, "score": 7.8142991065979}, {"content": "Title: Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia Content: In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19. One Sentence Summary New insights on SARS-CoV-2 biology and drug combination therapies against COVID-19.", "qid": 30, "docid": "bw9lbzvt", "rank": 63, "score": 7.779099941253662}, {"content": "Title: Antivirals for COVID-19. Content: Drugs targeting RNA respiratory viruses has resulted in few effective therapies, highlighting challenges for antivirals to treat COVID-19. Several antivirals are being investigated for symptomatic COVID-19 but no definitive data support their clinical use. Remdesivir, with good in vitro activity against SARS-CoV2, appeared to result in favorable outcomes for hospitalized patients in a compassionate use series with shortened time to recovery and a modest decrease in mortality. Currently, remdesivir is available in phase III clinical trials, the compassionate use program, and eventually through the emergency use authorization. A randomized controlled trial of lopinavir/ritonavir demonstrated no apparent clinical or virologic benefit and drug-drug interactions and side effects further limit its utility. Antivirals to treat influenza (oseltamivir) have limited activity against SARS-CoV-2, but favipiravir and umifenovir, influenza antivirals available internationally, have distinct viral targets and require further investigation. Antivirals with evidence of clinical activity must be studied as treatment and prophylaxis for those at high risk for severe COVID-19.", "qid": 30, "docid": "eaqxifxu", "rank": 64, "score": 7.766499996185303}, {"content": "Title: Geneesmiddelen bij COVID-19./ [Medication and comedication in COVID-19 patients] Content: This paper discusses the possible effects of comedication on COVID-19 and the current treatment options for this infection. It is very doubtful that comedication has a disadvantageous effect on the course of the disease. NSAIDs should be avoided in any patient with a possible severe disease, because of potential side effects. Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems. There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors. Currently, chloroquine and remdesivir are possible treatment options. There is no sound evidence for either treatment. Chloroquine has side effects (nausea, QT prolongation) and there are several drug interactions. The treatment should be reconsidered in the event of side effects and when inferior medication for comorbidity must be prescribed because of possible interactions. Lopinavir/ritonavir is not effective. Supportive care is at present the mainstay of the treatment.", "qid": 30, "docid": "e3clp17r", "rank": 65, "score": 7.743000030517578}, {"content": "Title: Rapid review for the anti-coronavirus effect of remdesivir. Content: The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "qid": 30, "docid": "4el6qq3n", "rank": 66, "score": 7.725500106811523}, {"content": "Title: Rapid review for the anti-coronavirus effect of remdesivir Content: The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "qid": 30, "docid": "a0drmmf7", "rank": 67, "score": 7.725499153137207}, {"content": "Title: The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report Content: Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5\u00e2\u0080\u00afdays after initiation of remdesivir, was transitioned to room air 24\u00e2\u0080\u00afh later, and discharged at the completion of remdesivir therapy.", "qid": 30, "docid": "6wwmbgw7", "rank": 68, "score": 7.7204999923706055}, {"content": "Title: The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report Content: Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5 days after initiation of remdesivir, was transitioned to room air 24 h later, and discharged at the completion of remdesivir therapy.", "qid": 30, "docid": "fxi8ss2s", "rank": 69, "score": 7.720499038696289}, {"content": "Title: Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status Content: SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged &#8805;18 years undergoing mechanical ventilation or with an oxygen saturation level of &#8804;94 % in air or a National Early Warning Score 2 of &#8805;4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "qid": 30, "docid": "pdc3bv33", "rank": 70, "score": 7.6875}, {"content": "Title: Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis Content: Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB\u2019s instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial\u2019s scientific integrity.", "qid": 30, "docid": "bz3i0q7a", "rank": 71, "score": 7.6869001388549805}, {"content": "Title: Can Zn Be a Critical Element in COVID-19 Treatment? Content: The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective anti-viral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.", "qid": 30, "docid": "efisqc5x", "rank": 72, "score": 7.652500152587891}, {"content": "Title: That Escalated Quickly: Remdesivir's Place in Therapy for COVID-19 Content: Remdesivir is a nucleoside antiviral recently studied in several randomized trials for treatment of COVID-19. The available observational and prospective data are conflicting, requiring clinicians to critically evaluate and reconcile results to determine patient populations that may optimally benefit from remdesivir therapy, especially while drug supply is scarce. In this review, we analyze pertinent clinical remdesivir data for patients with COVID-19 from January 1, 2020, through May 31, 2020.", "qid": 30, "docid": "ioqvxhar", "rank": 73, "score": 7.650300025939941}, {"content": "Title: [Medication and comedication in COVID-19 patients]. Content: This paper discusses the possible effects of comedication on COVID-19 and the current treatment options for this infection. It is very doubtful that comedication has a disadvantageous effect on the course of the disease. NSAIDs should be avoided in any patient with a possible severe disease, because of potential side effects. Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems. There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors. Currently, chloroquine and remdesivir are possible treatment options. There is no sound evidence for either treatment. Chloroquine has side effects (nausea, QT prolongation) and there are several drug interactions. The treatment should be reconsidered in the event of side effects and when inferior medication for comorbidity must be prescribed because of possible interactions. Lopinavir/ritonavir is not effective. Supportive care is at present the mainstay of the treatment.", "qid": 30, "docid": "0svdq020", "rank": 74, "score": 7.642300128936768}, {"content": "Title: Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection Content: The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.", "qid": 30, "docid": "x1fzgiy6", "rank": 75, "score": 7.632699966430664}, {"content": "Title: Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection Content: The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV\u2212induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.", "qid": 30, "docid": "x50tvq3a", "rank": 76, "score": 7.632699012756348}, {"content": "Title: Compassionate Use of Remdesivir for Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).", "qid": 30, "docid": "kxds6r7t", "rank": 77, "score": 7.6234002113342285}, {"content": "Title: Compassionate Use of Remdesivir for Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)", "qid": 30, "docid": "oyr4klqk", "rank": 78, "score": 7.623399257659912}, {"content": "Title: How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19 Content: Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan-Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.", "qid": 30, "docid": "96xerchf", "rank": 79, "score": 7.587200164794922}, {"content": "Title: How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19 Content: Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan\u2013Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.", "qid": 30, "docid": "vdypu76r", "rank": 80, "score": 7.5871992111206055}, {"content": "Title: Treatment options for COVID-19: the reality and challenges Content: Abstract An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.", "qid": 30, "docid": "j8n06hzx", "rank": 81, "score": 7.583600044250488}, {"content": "Title: Treatment options for COVID-19: The reality and challenges Content: An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.", "qid": 30, "docid": "qsd49pvm", "rank": 82, "score": 7.583599090576172}, {"content": "Title: Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post_treatment hospitalisation status Content: SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged \u226518 years undergoing mechanical ventilation or with an oxygen saturation level of \u226494% in air or a National Early Warning Score 2 of \u22654. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "qid": 30, "docid": "nzxbogga", "rank": 83, "score": 7.583000183105469}, {"content": "Title: Statistical Issues and Lessons Learned from COVID-19 Clinical Trials with Lopinavir-Ritonavir and Remdesivir Content: Background: Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in December 2019, it has rapidly spread in more than 200 countries or territories with over 8 million confirmed cases and 440,000 deaths by June 17, 2020. Recently, three randomized clinical trials on COVID-19 treatments were completed, one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. However, several statistical issues in the original design and analysis of the three trials are identified, which might shed doubts on their findings and the conclusions should be evaluated with cautions. Objective: From statistical perspectives, we identify several issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. Methods: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al. failed to reach the planned sample size due to a lack of eligible patients, while the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) in this context to analyze the reconstructed data due to the existence of death as competing risk and a terminal event. The remdesivir trial of Beigel et al. reported the median recovery time of the remdesivir and placebo groups and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We reanalyzed the data to report other percentiles of the time to recovery and adopted the bootstrap method and permutation test to construct the confidence intervals as well as the P values. The restricted mean time to recovery (RMTR) was also computed as a global and robust measure for efficacy. Results: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of terminal rates was -8.74% (95% CI [-21.04, 3.55]; P=.16) and the hazards ratio (HR) adjusted for terminal rates was 1.05 (95% CI [0.78, 1.42]; P=.74), indicating no significant difference. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI [-3.62, 0.28]; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al., the difference of terminal rates was -0.89% (95% CI [-2.84, 1.06]; P=.19) and the HR adjusted for terminal rates was 0.92 (95% CI [0.63, 1.35]; P=.67). The difference of RMTIs at day 28 was -0.89 day (95% CI [-2.84, 1.06]; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the HR estimates would reach statistical significance if the target sample size had been maintained, and both conditional and unconditional prediction delivered significant HR results if the trial had continued to double the target sample size. For the remdesivir trial of Beigel et al., the difference of RMTRs between the remdesivir and placebo groups up to day 30 was -2.7 days (95% CI [-4.0, -1.2]; P<.001), confirming the superiority of remdesivir. The difference in recovery time at the 25th percentile (95% CI [-3, 0]; P=.65) was insignificant, while the differences manifested to be statistically significant at larger percentiles. Conclusions: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis for ongoing and future COVID-19 trials.", "qid": 30, "docid": "nh9dzfpd", "rank": 84, "score": 7.559599876403809}, {"content": "Title: Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition Content: Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.", "qid": 30, "docid": "lbnfqv77", "rank": 85, "score": 7.553599834442139}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \"COVID 19,\" \"SARS-CoV-2,\" and \"treatment.\" All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 30, "docid": "4ehhtkfn", "rank": 86, "score": 7.528299808502197}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \u201cCOVID 19,\u201d \u201cSARS-CoV-2,\u201d and \u201ctreatment.\u201d All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Glucocorticoids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 30, "docid": "9ryu9ady", "rank": 87, "score": 7.528298854827881}, {"content": "Title: Antiviral treatment of COVID-19 Content: Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%\u00ad10% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.", "qid": 30, "docid": "4g878n13", "rank": 88, "score": 7.513199806213379}, {"content": "Title: Antiviral treatment of COVID-19 Content: Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%\u201310% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.", "qid": 30, "docid": "qq6l6yrx", "rank": 89, "score": 7.5131988525390625}, {"content": "Title: Harmonizing heterogeneous endpoints in COVID-19 trials without loss of information - an essential step to facilitate decision making Content: Background: Many trials are now underway to inform decision-makers on potential effects of treatments for COVID-19. To provide sufficient information for all involved decision-makers (clinicians, public health authorities, drug regulatory agencies) a multiplicity of endpoints must be considered. It is a challenge to generate detailed high quality evidence from data while ensuring fast availability and evaluation of the results. Methods: We reviewed all interventional COVID-19 trials on Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine registered in the National Library of Medicine (NLM) at the National Institutes of Health (NIH) and summarized the endpoints used to assess treatment effects. We propose a multistate model that harmonizes heterogeneous endpoints and differing lengths of follow-up within and between trials. Results: There are currently, March 27, 2020, 23 registered interventional trials investigating the potential benefits of Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine. The endpoints are highly heterogeneous. Follow-up for the primary endpoints ranges from four to 168 days. A detailed precisely defined endpoint has been proposed by the global network REMAP-CAP, which is specialized on community-acquired pneumonia. Their seven-category endpoint accounts for major clinical events informative for all decision-makers. Moreover, the Core Outcome Measures in Effectiveness Trials (COMET) Initiative is currently working on a core outcome set. We propose a multistate model that accommodates analysis of these recommended endpoints. The model allows for a detailed investigation of treatment effects for various endpoints over the course of time thereby harmonizing differing endpoints and lengths of follow-up. Conclusion: Multistate model analysis is a powerful tool to study clinically heterogeneous endpoints (mortality, discharge) as well as endpoints influencing hospital capacities (duration of hospitalization and ventilation) simultaneously over time. Our proposed model extracts all information available in the data and is - by harmonizing endpoints within and between trials - a step towards faster decision making. All ongoing clinical trials, especially those with severe cases, should accommodate primary analysis with a stacked probability plot of the major events mechanical ventilation, discharge alive and death.", "qid": 30, "docid": "bsddxgx2", "rank": 90, "score": 7.499899864196777}, {"content": "Title: Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19 Content: An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.", "qid": 30, "docid": "byjd8w4c", "rank": 91, "score": 7.4868998527526855}, {"content": "Title: Remdesivir inhibits renal fibrosis in obstructed kidneys Content: Aim Kidney impairment is observed in patients with COVID-19. We aimed to demonstrate the effect of anti-COVID-19 agent remdesivir on renal fibrosis. Methods Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-\u03b2 stimulated renal fibroblasts (NRK-49F) and human renal epithelial cells (HK2). Cell viability was determined by CCK8 assay, and fibrotic markers were measured by Western blotting. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson\u2019s trichrome staining and Western blotting. Results Remdesivir and GS-441524 inhibited cell proliferation and the expression of fibrotic markers (fibronectin, pSmad3, and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis of UUO kidneys. Renal and liver function were not changed in remdesivir treated UUO mice. Remdesivir can not be detected, but two remdesivir metabolites were detected after injection. Conclusion Remdesivir inhibits renal fibrosis in obstructed kidneys.", "qid": 30, "docid": "uc3slu8q", "rank": 92, "score": 7.453100204467773}, {"content": "Title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Content: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.", "qid": 30, "docid": "iymmf4k6", "rank": 93, "score": 7.444799900054932}, {"content": "Title: Simeprevir suppresses SARS-CoV-2 replication and synergizes with remdesivir Content: The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a global threat to human health. By in vitro screening and biochemical characterization, we identified the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. We also revealed that simeprevir synergizes with the RNA-dependent RNA polymerase (RdRP) inhibitor remdesivir to suppress the replication of SARS-CoV-2 in vitro. Our results provide preclinical rationale for the combination treatment of simeprevir and remdesivir for the pharmacological management of COVID-19 patients. One Sentence Summary Discovery of simeprevir as a potent suppressor of SARS-CoV-2 viral replication that synergizes remdesivir.", "qid": 30, "docid": "6470qlu1", "rank": 94, "score": 7.431399822235107}, {"content": "Title: Old and re-purposed drugs for the treatment of COVID-19 Content: INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. AREAS COVERED: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. EXPERT OPINION: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.", "qid": 30, "docid": "hn12194u", "rank": 95, "score": 7.430300235748291}, {"content": "Title: Old and re-purposed drugs for the treatment of COVID-19. Content: Introduction: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated.Areas covered: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy.Expert opinion: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.", "qid": 30, "docid": "mbv8vb2r", "rank": 96, "score": 7.430299282073975}, {"content": "Title: Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19 Content: BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.", "qid": 30, "docid": "vachz4i9", "rank": 97, "score": 7.425300121307373}, {"content": "Title: Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action Content: The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a \u201cPublic Health Emergency of International Concern\u201d (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level.", "qid": 30, "docid": "nedsqmr0", "rank": 98, "score": 7.418499946594238}, {"content": "Title: Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action Content: The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a \"Public Health Emergency of International Concern\" (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level.", "qid": 30, "docid": "tsms3303", "rank": 99, "score": 7.418498992919922}, {"content": "Title: SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus Content: Here we report on the most recent updates on experimental drugs successfully em- ployed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxy- chloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experi- mental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this vi- rus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.", "qid": 30, "docid": "fgbilulc", "rank": 100, "score": 7.377200126647949}]}
{"query": "How does the coronavirus differ from seasonal flu?", "hits": [{"content": "Title: Experience of a screening centre for influenza A/H1N1: the first 50 days. Content: BACKGROUND The authors' emergency department (ED) served as Singapore's screening centre for influenza H1N1 cases. The aims of the study were to describe their screening experience and to compare clinical and laboratory features of H1N1 versus seasonal flu cases. METHODOLOGY The authors conducted a prospective observational study on consecutive patients aged 16 years and above presenting to a busy, urban ED for H1N1 screening over 50 days. Clinical, laboratory, radiological and PCR data were collected from the hospital electronic databases. Primary outcomes were proportions of confirmed H1N1 cases and their distribution of clinical, laboratory and radiological features. Secondary outcomes were comparison of clinical and laboratory features of H1N1 versus seasonal flu cases. Data were analysed using descriptive statistics and univariate analysis was used to compare factors between the two groups. A p value <0.05 was considered statistically significant. RESULTS 1205 patients were screened. 31 (2.6%) and 133 (11%) of them had H1N1 and seasonal flu infections, respectively. The two groups had similar symptoms. There were six clinical and two laboratory features with statistically significant differences between H1N1 and seasonal flu cases. Clinical factors were travel or contact history, median age, respiratory rate, diastolic blood pressure and length of hospital stay. Laboratory factors were median platelet and lymphocyte counts. CONCLUSIONS The authors report their experience as the nation's H1N1 screening centre. They identified factors that were different between H1N1 and seasonal flu cases. Future research is needed to elucidate if and how this information can be used as a screening tool for H1N1.", "qid": 31, "docid": "aksjrr8g", "rank": 1, "score": 10.512999534606934}, {"content": "Title: Understanding Coronavirus Content: Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience", "qid": 31, "docid": "hmvo5b0q", "rank": 2, "score": 10.022899627685547}, {"content": "Title: Pollen Explains Flu-Like and COVID-19 Seasonality Content: Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral and allergenic, play a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19. We tested the Pollen-Flu Seasonality Theory for 2016-2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data for the same period. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence. We found a highly significant inverse association of r(224)= -.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = -.48 (p < .001) when pollen thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation threshold of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases. We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.", "qid": 31, "docid": "8ndl8zjz", "rank": 3, "score": 9.482600212097168}, {"content": "Title: Modelling the Extremes of Seasonal Viruses and Hospital Congestion: The Example of Flu in a Swiss Hospital Content: Viruses causing flu or milder coronavirus colds are often referred to as\"seasonal viruses\"as they tend to subside in warmer months. In other words, meteorological conditions tend to impact the activity of viruses, and this information can be exploited for the operational management of hospitals. In this study, we use three years of daily data from one of the biggest hospitals in Switzerland and focus on modelling the extremes of hospital visits from patients showing flu-like symptoms and the number of positive cases of flu. We propose employing a discrete Generalized Pareto distribution for the number of positive and negative cases, and a Generalized Pareto distribution for the odds of positive cases. Our modelling framework allows for the parameters of these distributions to be linked to covariate effects, and for outlying observations to be dealt with via a robust estimation approach. Because meteorological conditions may vary over time, we use meteorological and not calendar variations to explain hospital charge extremes, and our empirical findings highlight their significance. We propose a measure of hospital congestion and a related tool to estimate the resulting CaRe (Charge-at-Risk-estimation) under different meteorological conditions. The relevant numerical computations can be easily carried out using the freely available GJRM R package. The introduced approach could be applied to several types of seasonal disease data such as those derived from the new virus SARS-CoV-2 and its COVID-19 disease which is at the moment wreaking havoc worldwide. The empirical effectiveness of the proposed method is assessed through a simulation study.", "qid": 31, "docid": "ziujiigl", "rank": 4, "score": 9.436800003051758}, {"content": "Title: The utility of preemptive mass influenza vaccination in controlling a sars outbreak during flu season. Content: During flu season, respiratory infections can cause non-specific influenza-like-illnesses (ILIs) in up to one-half of the general population. If a future SARS outbreak were to coincide with flu season, it would become exceptionally difficult to distinguish SARS rapidly and accurately from other ILIs, given the non-specific clinical presentation of SARS and the current lack of a widely available, rapid, diagnostic test. We construct a deterministic compartmental model to examine the potential impact of preemptive mass influenza vaccination on SARS containment during a hypothetical SARS outbreak coinciding with a peak flu season. Our model was developed based upon the events of the 2003 SARS outbreak in Toronto, Canada. The relationship of different vaccination rates for influenza and the corresponding required quarantine rates for individuals who are exposed to SARS was analyzed and simulated under different assumptions. The study revealed that a campaign of mass influenza vaccination prior to the onset of flu season could aid the containment of a future SARS outbreak by decreasing the total number of persons with ILIs presenting to the health-care system, and consequently decreasing nosocomial transmission of SARS in persons under investigation for the disease.", "qid": 31, "docid": "uer59ad3", "rank": 5, "score": 9.38759994506836}, {"content": "Title: Development and verification of real-time PCR assay for identification of viral agents causing acute respiratory infections in human beings Content: A multiplex polymerase chain reaction (PCR) for identification of four viruses causing acute respiratory diseases in human beings was developed. The analytical sensitivity of developed RT-PCR for identification of adenovirus, respiratory-syncytial virus, flu viruses types A and B, and actual subtypes of type A flu virus (seasonal and pandemic variants H1N1, seasonal H3N2, and viruses of bird flu that are pathogenic to human beings H5 and H7) was 1 \u00d7 10(3) genome equivalents per milliliter. Diagnostic sensitivity for flu virus type A and B, and also subtypes H1 (seasonal H1N1, pandemic variant of H1N1 of year 2009), H3, H5 was 1 \u00d7 10(3)\u201310(4) viral particles per milliliter. The method developed has high specificity and does not have positive signal in experiments with DNA/cDNA of human beings and viral DNA. We have studied 50 samples using the developed set. Etiology was defined in 33 samples.", "qid": 31, "docid": "b3hbk43r", "rank": 6, "score": 9.353699684143066}, {"content": "Title: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends Content: BACKGROUND: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. METHODS AND FINDINGS: Influenza activity data from 2003\u201304 through 2007\u201308 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003\u201304 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). CONCLUSIONS: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003\u201304 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.", "qid": 31, "docid": "nge1itgk", "rank": 7, "score": 9.294099807739258}, {"content": "Title: Public views of the uk media and government reaction to the 2009 swine flu pandemic Content: BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.", "qid": 31, "docid": "mg2zikyp", "rank": 8, "score": 9.231599807739258}, {"content": "Title: Forecasting the 2013\u20132014 Influenza Season Using Wikipedia Content: Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.", "qid": 31, "docid": "9sgrw1qp", "rank": 9, "score": 9.229999542236328}, {"content": "Title: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID\u201019? Content: The recent 2019\u2010novel coronavirus (2019\u2010nCoV, also known as SARS\u2010CoV\u20102) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID\u201019) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019\u2010nCoV. Prior to the present pandemic of COVID\u201019, there have been multiple large\u2010scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face\u2010to\u2010face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.", "qid": 31, "docid": "oe7ovqw2", "rank": 10, "score": 9.128000259399414}, {"content": "Title: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID-19? Content: The recent 2019-novel coronavirus (2019-nCoV, also known as SARS-CoV-2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID-19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019-nCoV. Prior to the present pandemic of COVID-19, there have been multiple large-scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face-to-face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.", "qid": 31, "docid": "s3s7b3j2", "rank": 11, "score": 9.127999305725098}, {"content": "Title: Environmental factors and seasonal influenza onset in Okayama city, Japan: case-crossover study. Content: Seasonal influenza infection is a major challenge in public health. The term \"seasonal influenza\" refers to the typical increase in the number of influenza patients in the winter season in temperature zones. However, it is not clear how environmental factors within a single flu season affect influenza infection in a human population. Therefore, we evaluated the effects of temperature and humidity in the 2006-7 flu season on the onset of seasonal influenza using a case-crossover study. We targeted patients who attended one pediatric clinic in Okayama city, Japan and who were diagnosed as being infected with the seasonal influenza virus. Using 2 references (time-stratified and symmetric bidirectional design), we estimated the effects of average temperature and relative humidity from the onset day (lag0) to 10 days before (lag10). The total number of subjects was 419, and their onset days ranged from 26 December 2006 to 30 April 2007. While the onset was significantly associated with lower temperature, relative humidity was not related. In particular, temperatures before the 3-day incubation period had higher-magnitude odds ratios. For example, the odds ratio and 95% confidence interval for average temperature at time lag 8 was 1.12 (1.08-1.17) per 1.0\u2103 decrease. Low environmental temperature significantly increased the risk of seasonal influenza onset within the 2006-7 winter season.", "qid": 31, "docid": "tnrfquse", "rank": 12, "score": 9.103599548339844}, {"content": "Title: Subsequent waves of viral pandemics, a hint for the future course of the SARS-CoV-2 pandemic. Content: Background It is unknown if the SARS-CoV-2 pandemic will have a second wave. We analysed published data of five influenza pandemics (such as the Spanish Flu and the Swine Flu) and the SARS-CoV-1 pandemic to describe whether there were subsequent waves and how they differed. Methods We reanalysed literature and WHO reports on SARS-CoV-1 and literature on five influenza pandemics. We report frequencies of second and third waves, wave heights, wavelengths and time between subsequent waves. From this, we estimated peak-to-peak ratios to compare the wave heights, and wave-length-to-wave-length ratios to compare the wavelengths differences in days. Furthermore, we analysed the seasonality of the wave peaks and the time between the peak values of two waves. Results Second waves, the Spanish Flu excluded, were usually about the same height and length as first waves and were observed in 93% of the 57 described epidemic events of influenza pandemics and in 42% of the 19 epidemic events of the SARS-CoV-1 pandemic. Third waves occurred in 54% of the 28 influenza and in 11% of the 19 SARS-CoV-1 epidemic events. Third waves, the Spanish Flu excluded, usually peaked higher than second waves with a peak-to-peak ratio of 0.5. Conclusion While influenza epidemics are usually accompanied by 2nd waves, this is only the case in the minority of SARS-Cov1 epidemics.", "qid": 31, "docid": "c44cbfvt", "rank": 13, "score": 9.04259967803955}, {"content": "Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\") Content: BACKGROUND: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 (\"Swine flu\") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. METHODS: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption RESULTS: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. CONCLUSION: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.", "qid": 31, "docid": "0ybn2igj", "rank": 14, "score": 8.986599922180176}, {"content": "Title: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics Content: BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as \"bridge regions\" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.", "qid": 31, "docid": "dqxnc5o0", "rank": 15, "score": 8.978799819946289}, {"content": "Title: Influenza species and subtypes circulation among hospitalized patients in Laleh hospital during two influenza seasonal (2016-2017 and 2017-2018) using a multiplex Real Time-Polymerase Chain Reaction Content: The introduction of polymerase chain reaction (PCR) techniques has improved the detection of respiratory viruses, particularly with the use of multiplex real-time technique with the capability of simultaneous detection of various pathogens in a single reaction. The aim of this study was to apply the above technology for the diagnosis of influenza infections and at the same time to differentiate between common flu species between hospitalized patients in Laleh hospital (Iran) between two flu seasons (2016-2017 and 2017-2018). Different respiratory specimens were collected from 540 patients from a period of December 2016 to May 2018 and were sent to the laboratory for molecular diagnosis. RNAs were extracted and subsequently, a multiplex real time PCR identifying flu A, flu B and typing flu A (H1N1) was carried out. The mean age of patients was 47.54\u00b123.96. 216 (40%) and 321 (60%) of subjects were male and female, respectively. 219 out of 540 (40.5%) were positive for influenza infection including flu A (n=97, 44.3%), flu A (H1N1) (n=45, 20.7%) and flu B (n=77, 35%). Flu A was the dominant species on 2016-2017 and flu B was the major species on 2017-2018. Flu A (H1N1) was comparable in both time periods. Flu infections were most frequently diagnosed in age groups 21-40. Flu-positive patients suffered more from body pain and sore throat than flunegative patients with significant statistical difference (P values <0.001). The mean duration of hospitalization was shorter for flu-positive patients (P value = 0.016). Application of multiplex real time PCR could facilitate the influenza diagnosis in a short period of time, benefiting patients from exclusion of bacterial infections and avoiding unnecessary antibiotic therapy. Influenza diagnosis was not achieved in up to 60% of flu-like respiratory infections, suggesting the potential benefit of adopting the same methodology for assessing the involvement of other viral or/and bacterial pathogens in those patients.", "qid": 31, "docid": "1ykji0c8", "rank": 16, "score": 8.971099853515625}, {"content": "Title: Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016-2019 Content: There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.", "qid": 31, "docid": "q4sm3oy9", "rank": 17, "score": 8.875300407409668}, {"content": "Title: Incidence and seasonality of respiratory viruses causing acute respiratory infections in the Northern United Arab Emirates Content: BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)\u2010related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real\u2010time reverse transcription polymerase chain reaction (rRT\u2010PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT\u2010PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak\u2010to\u2010low ratio for FLU was 2.26 (95% confidence interval: 1.52\u20103.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi\u2010seasonal pattern in the UAE.", "qid": 31, "docid": "m1j6v33y", "rank": 18, "score": 8.840900421142578}, {"content": "Title: Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016\u20132019 Content: Abstract There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.", "qid": 31, "docid": "qwub35cd", "rank": 19, "score": 8.834600448608398}, {"content": "Title: SARS vs. flu: can you tell serious disease from common malady? Content: Health officials caution that severe acute respiratory syndrome (SARS) may return this fall with the flu season, and the serious disease may be difficult to distinguish from the common malady. Paying attention to public health trends will help you determine how much a diagnosing concern SARS should be in your own ED. More use of rapid diagnostic tests for flu may help, but don't depend too much on them. Confirming a flu diagnosis means you're relatively safe in ruling out SARS. ED physicians may have to be overly cautious this year in identifying cases of potential SARS.", "qid": 31, "docid": "pnl2w4mf", "rank": 20, "score": 8.82349967956543}, {"content": "Title: Does this patient have COVID-19? A practical guide for the internist Content: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its 'semeiotic'. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.", "qid": 31, "docid": "evv73ry1", "rank": 21, "score": 8.700499534606934}, {"content": "Title: Does this patient have COVID-19? A practical guide for the internist Content: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its \u2018semeiotic\u2019. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.", "qid": 31, "docid": "t98ctnc2", "rank": 22, "score": 8.700498580932617}, {"content": "Title: Traumatic Times Content: Discusses how businesses are impacted by traumatic events and pandemics such as the current Coronavirus (COVID-19) As I write this in late March, we are early in the coronavirus (COVID-19) pandemic It is like nothing any of us have experienced before, except perhaps the very few who may have lived through the flu pandemic of 1918-1920 The COVID-19 crisis is like a combination of all the worst we've seen There is social trauma as we isolate ourselves, lose some individual liberties, and try to work from home We don't know when society will return to normal and, when it does, how it will have changed", "qid": 31, "docid": "uczrmgq3", "rank": 23, "score": 8.694600105285645}, {"content": "Title: The complex associations of climate variability with seasonal influenza A and B virus transmission in subtropical Shanghai, China Content: Abstract Most previous studies focused on the association between climate variables and seasonal influenza activity in tropical or temperate zones, little is known about the associations in different influenza types in subtropical China. The study aimed to explore the associations of multiple climate variables with influenza A (Flu-A) and B virus (Flu-B) transmissions in Shanghai, China. Weekly influenza virus and climate data (mean temperature (MeanT), diurnal temperature range (DTR), relative humidity (RH) and wind velocity (Wv)) were collected between June 2012 and December 2018. Generalized linear models (GLMs), distributed lag non-linear models (DLNMs) and regression tree models were developed to assess such associations. MeanT exerted the peaking risk of Flu-A at 1.4 \u00b0C (2-weeks\u2019 cumulative relative risk (RR): 14.88, 95% confidence interval (CI): 8.67\u201323.31) and 25.8 \u00b0C (RR: 12.21, 95%CI: 6.64\u201319.83), Flu-B had the peak at 1.4 \u00b0C (RR: 26.44, 95%CI: 11.52\u201351.86). The highest RR of Flu-A was 23.05 (95%CI: 5.12\u201388.45) at DTR of 15.8 \u00b0C, that of Flu-B was 38.25 (95%CI: 15.82\u201387.61) at 3.2 \u00b0C. RH of 51.5% had the highest RR of Flu-A (9.98, 95%CI: 4.03\u201326.28) and Flu-B (4.63, 95%CI: 1.95\u201311.27). Wv of 3.5 m/s exerted the peaking RR of Flu-A (7.48, 95%CI: 2.73\u201330.04) and Flu-B (7.87, 95%CI: 5.53\u201311.91). DTR \u2265 12 \u00b0C and MeanT <22 \u00b0C were the key drivers for Flu-A and Flu-B, separately. The study found complex non-linear relationships between climate variability and different influenza types in Shanghai. We suggest the careful use of meteorological variables in influenza prediction in subtropical regions, considering such complex associations, which may facilitate government and health authorities to better minimize the impacts of seasonal influenza.", "qid": 31, "docid": "0oqcx0az", "rank": 24, "score": 8.64210033416748}, {"content": "Title: Analyses of Merging Clinical and Viral Genetic Data for Influenza Surveillance. Content: The annual influenza vaccine is one of the most common public health interventions and is universally recommended for all individuals older than six months. Vaccine composition depends on viruses circulating over the past flu season and are estimated to be the most prevalent and representative strains in the current season. Here, we use clinical data outfitted with viral genetics to characterize confirmed influenza cases from the past two flu seasons and genetically compare them to the strains that they were vaccinated against that year. We show that case similarities to vaccine strains differ by geographic region and that the vaccines appear to have different levels of effectiveness by region. This study demonstrates the value of merging viral genetics with clinical data. Further research is needed to formally evaluate whether this improves biosurveillance efforts and enhances efficacy of influenza vaccines.", "qid": 31, "docid": "k1ysvz82", "rank": 25, "score": 8.602399826049805}, {"content": "Title: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020 Content: OBJECTIVES: Infection due to the 2019 novel coronavirus disease (COVID-19) is dramatically widespread around the world. The COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and the potential decrease in seasonal influenza cases. METHODS: This study was performed to show trends in seasonal influenza cases from the 2014-2015 season to the 2019-2020 season in 11 countries and regions, and evaluate whether the trends in the 2019-2020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. RESULTS: In East Asia, the number of seasonal influenza cases in the 2019-20 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in American countries or in European countries. CONCLUSION: The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.", "qid": 31, "docid": "l11puhp4", "rank": 26, "score": 8.60159969329834}, {"content": "Title: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020 Content: Abstract Objectives Infection due to the 2019 novel coronavirus disease (COVID-19) is widespread dramatically around the world. This COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and decreasing another infectious disease. Methods This study was performed to show trends in seasonal influenza cases from the 2014\u20132015 season to the 2019\u20132020 season in 11 countries and regions, and evaluate whether the trends in the 2019\u20132020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. Results In East Asia, the number of seasonal influenza cases in the 2019\u201320 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in the American countries or in European countries. Conclusion The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.", "qid": 31, "docid": "luloic87", "rank": 27, "score": 8.565899848937988}, {"content": "Title: Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic Content: BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009\u20132010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-\u03b3 responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-\u03b3 production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-\u03b3 production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-\u03b3 production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.", "qid": 31, "docid": "i7v9l6ii", "rank": 28, "score": 8.520999908447266}, {"content": "Title: Typical epidemiology of respiratory virus infections in a Brazilian slum Content: Host population size, density, immune status, age structure, and contact rates are critical elements of virus epidemiology. Slum populations stand out from other settings and may present differences in the epidemiology of acute viral infections. We collected nasopharyngeal specimens from 282 children aged \u22645 years with acute respiratory tract infection (ARI) during 2005 to 2006 in one of the largest Brazilian slums. We conducted real\u2010time reverse transcription\u2010polymerase chain reaction (RT\u2010PCR) for 16 respiratory viruses, nested RT\u2010PCR\u2010based typing of rhinoviruses (HRVs), and collected clinical symptoms. Viruses were common causes of respiratory disease; with \u22651 virus being detected in 65.2% of patients. We detected 15 different viruses during 1 year with a predomidnance of HRV (33.0%) and human respiratory syncytial virus (hRSV, 12.1%) infections, and a high rate of viral coinfections (28.3%). We observed seasonality of hRSV, HRV and human coronavirus infections, more severe symptoms in hRSV and influenza virus (FLU) infections and prolonged circulation of seven HRV clusters likely representing distinct serotypes according to genomic sequence distances. Potentially unusual findings included the absence of human metapneumovirus detections and lack of typical FLU seasonal patterns, which may be linked to the population size and density of the slum. Nonetheless, most epidemiological patterns were similar to other studies globally, suggesting surprising similarities of virus\u2010associated ARI across highly diverse settings and a complex impact of population characteristics on respiratory virus epidemiology.", "qid": 31, "docid": "vo755hxj", "rank": 29, "score": 8.475199699401855}, {"content": "Title: An econometric analysis of SARS and Avian Flu on international tourist arrivals to Asia Content: Abstract This paper compares the impacts of SARS and human deaths arising from Avian Flu on international tourist arrivals to Asia. The effects of SARS and human deaths from Avian Flu are compared directly according to the number of human deaths. The nature of the short run and long run relationship is examined empirically by estimating a static line fixed effect model and a difference transformation dynamic model, respectively. Empirical results from the static fixed effect and difference transformation dynamic models are consistent, and indicate that both the short run and long run SARS effect have a more significant impact on international tourist arrivals than does Avian Flu. In addition, the effects of deaths arising from both SARS and Avian Flu suggest that SARS is more important to international tourist arrivals than is Avian Flu. Thus, while Avian Flu is here to stay, its effect is currently not as significant as that of SARS.", "qid": 31, "docid": "0ln9r2nq", "rank": 30, "score": 8.469499588012695}, {"content": "Title: News coverage of health-related issues and its impacts on perceptions: Taiwan as an example. Content: This article examines how health news gets framed and the influence of exposure to news framed differently. A content analysis of Taiwanese newspapers indicates that health news in general, and H1N1 flu news in particular, is more likely to use alarm rather than coping frames. According to an experiment, exposure to H1N1 flu news in an alarm frame evokes greater fear and increases perceived severity and vulnerability, though it does not help develop prevention and treatment efficacy. A survey of the general public also shows that attention and exposure to televised news coverage of the H1N1 flu are associated with greater levels of worry and perceptions of the severity of and vulnerability to this health problem, but they are not related to issue knowledge, detection, or prevention efficacy. Thus, it is important for news coverage to provide information that increases the audience's efficacy when alerting it to health threats.", "qid": 31, "docid": "n1vn4fuy", "rank": 31, "score": 8.447199821472168}, {"content": "Title: Factors in vaccination intention against the pandemic influenza A/H1N1 Content: Background: Vaccination against pandemic influenza A/H1N1 is an effective strategy to mitigate the spread of the disease. While the vaccine is now available, social acceptance remains relatively uncertain in many societies. The purpose of this study was to examine the beliefs, attitudes and practices associated with the intention to get vaccinated against the A/H1N1 virus among the general population in France. Methods: A representative sample of 1001 individuals (stratified random recruitment procedure, ages 16\u201390 years) was interviewed by telephone. The questionnaire included a variety of items associated with socio-demographic characteristics, risk perceptions, illness perceptions, political attitudes and worldviews as well as intention to get vaccinated. Results: More than 6 out of 10 of the respondents indicated that they planned to get vaccinated when the vaccine becomes available. The same proportion of parents also reported the intention to vaccinate their children against the disease. In multiple regression analyses, socio-cognitive factors consistently predicting influenza A/H1N1 vaccination were: level of worry, risk perception and previous experience of vaccine against seasonal flu. Conclusions: The factors found to predict vaccination intention and their distribution are assumed to be a consequence of the fact that people perceive the risk of swine flu to be similar to that of seasonal flu. As a result, in the absence of an increase of the risk perception of pandemic influenza A/H1N1, a very low level of actual vaccination is forecasted. Behavioural change would require that the risks and consequences of pandemic influenza A/H1N1 be perceived as highly different from seasonal flu.", "qid": 31, "docid": "334qzbqk", "rank": 32, "score": 8.430100440979004}, {"content": "Title: Hospital Associated Respiratory Virus Infection in Children and Adults: It Does Not Just Occur During Cold and Flu Season Content: Hospital-associated respiratory virus infections (HARVI) are an underappreciated source of morbidity and mortality. We examined HARVI incidence and clinical respiratory virus testing practices in a cohort of hospitalized patients with acute respiratory illness. HARVI were identified in patients of all ages, both during and outside of the influenza season.", "qid": 31, "docid": "8f6n5m2y", "rank": 33, "score": 8.354999542236328}, {"content": "Title: Assessing the interactions between COVID-19 and influenza in the United States Content: The 2019\u20132020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019\u20132020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019\u20132020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019\u20132020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal.", "qid": 31, "docid": "f3ds1rq6", "rank": 34, "score": 8.305399894714355}, {"content": "Title: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020. Content: Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.", "qid": 31, "docid": "wtqwghon", "rank": 35, "score": 8.305398941040039}, {"content": "Title: Ingestion of Exopolymers from Aureobasidium pullulans Reduces the Duration of Cold and Flu Symptoms: A Randomized, Placebo-Controlled Intervention Study Content: AIM: The objective of the study was to assess the efficacy of exopolymers from Aureobasidium pullulans (EAP) on the incidence of colds and flu in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 76 subjects (30\u201370 years of age) were recruited from the general population. The subjects were instructed to take one capsule per day of either EAP or a placebo for a period of 8 weeks. The duration of cold and flu symptoms, a primary variable in assessing effectiveness, and serum cytokine levels as well as WBC counts as secondary variables were also evaluated. RESULTS: EAP was associated with a statistically significant decrease in the duration of cold and flu symptoms, a primary variable in assessing effectiveness. Although cold and flu symptom levels were not significantly different at a significance level of 5%, the cold and flu symptom levels of the EAP group were less severe compared to the placebo group. No statistically significant changes of serum cytokine levels as well as WBC counts were observed. CONCLUSION: The results showed that EAP is a useful pharmaceutical and functional food material for preventing and treating colds and flu.", "qid": 31, "docid": "ktet18wl", "rank": 36, "score": 8.144100189208984}, {"content": "Title: Flu or a Bug? Content: Of late, apart from the four calendar seasons, there is yet another season referred to as the \u201cflu season.\u201d During this time of the year, we routinely hear the phrase \u201cthe flu is going around.\u201d I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word \u201cbug\u201d is used so callously by adults that it has been registered wrongly in the minds of the little ones.", "qid": 31, "docid": "lj34u0hs", "rank": 37, "score": 7.934700012207031}, {"content": "Title: Does subsidy work? Price elasticity of demand for influenza vaccination among the elderly in Japan Content: Abstract Objectives Subsidy for influenza vaccination is often provided to the elderly in order to encourage them to receive a flu shot in developed countries. However, its effect on uptake rate, i.e., price elasticity of demand, has not been well studied. Methods Japan's decentralised vaccination programme allows observation of various pairs in price and uptake rate of flu shots among the elderly by the municipality from 2001/2002 to 2004/2005 season. We combine our sample survey data (n =281), which monitor price, subsidy and uptake rate, with published data on local characteristics in order to estimate price elasticity of demand with panel model. Results We find price elasticity of demand for influenza vaccine: nearly zero in nationwide, nearly zero in urban area, and \u22121.07 in rural area. Conclusions The results question the rationale for subsidy, especially in urban area. There are cases where maintaining or increasing the level of subsidy is not an efficient allocation of finite health care resources. When organising a vaccination programme, health manager should be careful about the balance between subsidy and other efforts in order to encourage the elderly to receive shots with price elasticity in mind.", "qid": 31, "docid": "xzmg7k4e", "rank": 38, "score": 7.922299861907959}, {"content": "Title: Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children Content: Background: Children have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS). Methods: This cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup). Findings: SARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55.6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66.9 -100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection. Interpretation: Prior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.", "qid": 31, "docid": "49q2xxkw", "rank": 39, "score": 7.888599872589111}, {"content": "Title: Reproduction of East-African bats may guide risk mitigation for coronavirus spillover Content: BACKGROUND: Bats provide important ecosystem services; however, current evidence supports that they host several zoonotic viruses, including species of the Coronaviridae family. If bats in close interaction with humans host and shed coronaviruses with zoonotic potential, such as the Severe Acute Respiratory Syndrome virus, spillover may occur. Therefore, strategies aiming to mitigate potential spillover and disease emergence, while supporting the conservation of bats and their important ecological roles are needed. Past research suggests that coronavirus shedding in bats varies seasonally following their reproductive cycle; however, shedding dynamics have been assessed in only a few species, which does not allow for generalization of findings across bat taxa and geographic regions. METHODS: To assess the generalizability of coronavirus shedding seasonality, we sampled hundreds of bats belonging to several species with different life history traits across East Africa at different times of the year. We assessed, via Bayesian modeling, the hypothesis that chiropterans, across species and spatial domains, experience seasonal trends in coronavirus shedding as a function of the reproductive cycle. RESULTS: We found that, beyond spatial, taxonomic, and life history differences, coronavirus shedding is more expected when pups are becoming independent from the dam and that juvenile bats are prone to shed these viruses. CONCLUSIONS: These findings could guide policy aimed at the prevention of spillover in limited-resource settings, where longitudinal surveillance is not feasible, by identifying high-risk periods for coronavirus shedding. In these periods, contact with bats should be avoided (for example, by impeding or forbidding people access to caves). Our proposed strategy provides an alternative to culling \u2013 an ethically questionable practice that may result in higher pathogen levels \u2013 and supports the conservation of bats and the delivery of their key ecosystem services.", "qid": 31, "docid": "6znmkvy9", "rank": 40, "score": 7.849800109863281}, {"content": "Title: Prevalence of respiratory viruses, including newly identified viruses, in hospitalised children in Austria Content: The aim of this epidemiological study was to determine the prevalence of respiratory viruses, including new viruses, in hospitalised children in Austria. Two hundred fourteen nasopharyngeal samples from hospitalised children were tested for the presence of viruses using cell culture and PCR and/or viral antigen assays. The results revealed a parainfluenza virus 1 (PIV1) outbreak that ended right before the onset of the influenza season, with nearly no overlapping, moderate respiratory syncytial virus (RSV) activity, and only a few adenoviruses. Human metapneumovirus (hMPV) was present in 14.5% of the total samples but was detected in combination with other viruses in only five cases: with PIV1 in three cases and with RSV in two cases. There were no cases of dual infection with hMPV and flu or adenovirus. This suggests that hMPV alone is a leading cause of hospitalisation in children under 1 year of age. Interestingly, hMPV, in contrast to RSV, coincided with PIV1 but was absent during the community outbreak of the flu. Samples were also tested for Mimiviridae, a group of newly described DNA viruses that are similar to Legionella spp., replicate in water amoebae, and also have been found in alveolar cells. However, mimivirus was detected neither in respiratory samples nor in amoebae-containing water samples, indicating that this particular type of virus is either not abundant or does not contribute to paediatric respiratory illnesses.", "qid": 31, "docid": "c3g3hrm2", "rank": 41, "score": 7.8414998054504395}, {"content": "Title: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability Content: The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and the other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.", "qid": 31, "docid": "9m10jl7r", "rank": 42, "score": 7.832399845123291}, {"content": "Title: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability Content: The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.", "qid": 31, "docid": "epzu032t", "rank": 43, "score": 7.832398891448975}, {"content": "Title: Fevers Are Rarest in the Morning: Could We Be Missing Infectious Disease Cases by Screening for Fever Then? Content: Body temperatures are less likely to reach the fever range in the morning, but it is unknown how this affects practice during disease outbreaks. We retrospectively investigated fever-range temperatures ([\u2265]100.4{degrees}F, [\u2265]38.0{degrees}C) during seasonal influenza outbreaks and the 2009 H1N1 (swine flu) pandemic, which have recently been used as preparatory models for coronavirus disease 2019 (COVID-19). Our analyses included a nationally representative sample of records from adult visits to US emergency departments (n=202,181) and data from a Boston emergency department (n=93,225). Fever-range temperatures were about half as common in the morning as in the evening, suggesting that morning temperatures can be much less diagnostic, and that revisions may be needed to the practice of once-daily temperature screens at morning arrival to workplaces and schools. Twice-daily screens could be a simple solution, but similar research is still needed on fevers in COVID-19 itself.", "qid": 31, "docid": "quf99rxo", "rank": 44, "score": 7.823299884796143}, {"content": "Title: Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal non-pandemic seasonal respiratory infections. Content: BACKGROUND/AIM Acute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. This study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides. METHODS Retrospective study in 200 lung tissue samples from children who had died from severe respiratory infections during 1985-2005. Immunoperoxidase assay was performed to detect the viruses that were most commonly associated with respiratory tract infections: influenza virus A (FLU A), influenza virus B (FLU B), respiratory syncytial virus (RSV), adenovirus (AdV) and parainfluenza virus (PIV) types 1, 2 and 3. RESULTS Viruses were detected in 71 (35.5%) cases. Most positive cases were observed in children younger than 6 months. In 42.3% of cases, only one virus was detected: 11 (36.7%) RSV; 7 (23.3%) AdV; 4 (13.3%) PIV2; 3 (10%) FLU A; 2 (6.7%) FLU B; 2 (6.7%) PIV3; and 1 (3.3%) PIV1. Co-infection with more than one virus was observed in 41 (57.7%) cases. No positive correlations were observed between the presence of viral antigens and seasonality of the infection, sex, age or histopathological findings. CONCLUSIONS Non-pandemic seasonal respiratory viruses are involved in a significant number of deaths in paediatric patients; these findings highlight the importance of laboratory investigation of these agents in patients hospitalised with severe acute respiratory infections.", "qid": 31, "docid": "0ui7t51g", "rank": 45, "score": 7.719799995422363}, {"content": "Title: Online Social Networks Flu Trend Tracker: A Novel Sensory Approach to Predict Flu Trends Content: Seasonal influenza epidemics cause several million cases of illnesses cases and about 250,000 to 500,000 deaths worldwide each year. Other pandemics like the 1918 \u201cSpanish Flu\u201d may change into devastating event. Reducing the impact of these threats is of paramount importance for health authorities, and studies have shown that effective interventions can be taken to contain the epidemics, if early detection can be made. In this paper, we introduce Social Network Enabled Flu Trends (SNEFT), a continuous data collection framework which monitors flu related messages on online social networks such as Twitter and Facebook and track the emergence and spread of an influenza. We show that text mining significantly enhances the correlation between online social network(OSN) data and the Influenza like Illness (ILI) rates provided by Centers for Disease Control and Prevention (CDC). For accurate prediction, we implemented an auto-regression with exogenous input (ARX) model which uses current OSN data and CDC ILI rates from previous weeks to predict current influenza statistics. Our results show that, while previous ILI data from the CDC offer a true (but delayed) assessment of a flu epidemic, OSN data provides a real-time assessment of the current epidemic condition and can be used to compensate for the lack of current ILI data. We observe that the OSN data is highly correlated with the ILI rates across different regions within USA and can be used to effectively improve the accuracy of our prediction. Therefore, OSN data can act as supplementary indicator to gauge influenza within a population and helps to discover flu trends ahead of CDC.", "qid": 31, "docid": "dg53ss0q", "rank": 46, "score": 7.711599826812744}, {"content": "Title: Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza Content: BACKGROUND: Since the turn of the century seven new respiratory viruses have infected man and two of these have resulted in worldwide epidemics. Both SARS Coronavirus which quickly spread to 29 countries in February 2003 and H1N1 swine influenza that recently spread from Mexico to 30 countries in three weeks represent major pandemic threats for mankind. Diagnostic assays are required to detect novel influenza strains with pandemic potential. OBJECTIVE: In this report we evaluate the ability of a multiplex PCR test (xTAG(\u2122)RVP) to detect new, \u201cnon-seasonal\u201d influenza viruses including the H1N1 swine influenza A/swine/California/04/2009. STUDY DESIGN: Laboratory based study using retrospective and prospective specimens. RESULTS: This multiplex PCR test detected the present of non-seasonal (non-H1, non-H3) influenza in 20 of 20 patients infected with H1N1 swine flu virus. In addition to detecting the current swine flu the xTAG(\u2122) RVP test detected the H5N1 A/Vietnam/1203/2004 high pathogenicity avian influenza virus that circulated in South East Asia in 2003 as well as 17 out of 17 influenza A viruses representing 11 HA subtypes isolated from birds, swine and horses not yet seen in the human population. CONCLUSION: Based on these results we believe that this molecular test can perform an important role as a sentinel test to detect novel non-seasonal influenza A viruses in patients presenting with influenza-like illness (ILI) and therefore act as an early warning system for the detection of future pandemic influenza threats.", "qid": 31, "docid": "ko0gp2nd", "rank": 47, "score": 7.704100131988525}, {"content": "Title: Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017\u20132018 influenza season Content: PURPOSE: Receiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined. RESULTS: We compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46\u20130.51). CONCLUSIONS: Receipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.", "qid": 31, "docid": "30r8zd0l", "rank": 48, "score": 7.672900199890137}, {"content": "Title: Swine flu update: bringing home the bacon. Content: In 6 weeks, swine influenza A(H1N1) virus has spread from 10 to 74 countries. Australia has the fifth highest number of cases and the third highest rate of infection among the top five affected nations. People who are hospitalised with or die from this novel virus are more likely to have predisposing risk factors. There is a predilection for younger age groups and sparing of older age groups. This may be a property of influenza A viruses in general rather than being specific to swine influenza A. If unchecked, the sheer number of cases may lead to much higher numbers of deaths and hospitalised patients than would normally be attributed to a standard influenza season. Paradoxically, the low case-fatality rate of the virus raises the question of how best to approach management of this outbreak. It is uncertain how an expected vaccine against the novel virus will be used.", "qid": 31, "docid": "v0m81d27", "rank": 49, "score": 7.613100051879883}, {"content": "Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak Content: BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures \u2265100.4 \u00b0F [\u226538.0 \u00b0C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn\u2013winter wave of the 2009\u20132010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010\u20132011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system\u2019s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.", "qid": 31, "docid": "ripmj8t9", "rank": 50, "score": 7.605199813842773}, {"content": "Title: H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix\u00ae vaccination Content: A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix\u00ae vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251\u2013265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.", "qid": 31, "docid": "vrbsbwgv", "rank": 51, "score": 7.589700222015381}, {"content": "Title: Detection of Influenza and Other Respiratory Viruses Carried Out in the Influenza Project \u2013 Monitoring Vaccine Effectiveness (I-MOVE) Content: The project Influenza Vaccine Effectiveness-Monitoring (I-MOVE) is part of the European research carried out by the ECDC (European Center for Disease Prevention and Control), aimed at monitoring the effectiveness of vaccination in Europe during the growing incidence of flu and influenza-like illnesses in the coming epidemic seasons. Laboratory studies using molecular RT-PCR biology methods for detection of genetic material of influenza virus and other respiratory viruses were performed by Voivodeship Sanitary-Epidemiological Stations in Poland. The validation of the results of swabs taken from the nose and throat were carried out in the Department of Influenza Research, National Influenza Center in Warsaw. The study involved 210 samples from patients across Poland. Positive results were recorded for 72.4 % of the samples; influenza virus type A was detected in 43 and type B in 38 cases, whereas in 71 cases other respiratory viruses were detected, which included Human parainfluenza virus type 1\u20134; Human respiratory syncytial virus type A and B; Human coronavirus 229E/NL63, OC43; Human rhinovirus type A, B, and C; Human enterovirus; and Human adenovirus. The results show that although influenza viruses predominated in the 2010/2011 season in Poland, other flu-like viruses also abounded.", "qid": 31, "docid": "7lu6c91t", "rank": 52, "score": 7.587399959564209}, {"content": "Title: Talking about colds and flu: The lay diagnosis of two common illnesses among older British people Content: This paper reports on a study of the ways in which 54 older people in South Wales (UK) talk about the symptoms and causes of cold and influenza (flu). The study was designed to understand why older people might reject or accept the offer of seasonal flu vaccine, and in the course of the interviews respondents were also asked to express their views about the nature and causes of the two key illnesses. The latter are among the most common infections in human beings. In terms of the biomedical paradigm the common cold is caused by numerous respiratory viruses, whilst flu is caused by the influenza virus. Medical diagnosis is usually made on clinical grounds without laboratory confirmation. Symptoms of flu include sudden onset of fever and cough, and colds are characterized by sneezing, sore throat, and runny nose, but in practice the symptoms often overlap. In this study we examine the degree by which the views of lay people with respect to both diagnosis and epidemiology diverge with that which is evident in biomedical discourse. Our results indicate that whilst most of the identified symptoms are common to lay and professional people, the former integrate symptoms into a markedly different observational frame from the latter. And as far as causation is concerned it is clear that lay people emphasize the role of \u2018resistance\u2019 and \u2018immunity\u2019 at least as much as \u2018infection\u2019 in accounting for the onset of colds and flu. The data are analyzed using novel methods that focus on the co-occurrence of concepts and are displayed as semantic networks. As well as reporting on its findings the authors draw out some implications of the study for social scientific and policy discussions concerning lay diagnosis, lay expertise and the concept of an expert patient.", "qid": 31, "docid": "uheb2cvg", "rank": 53, "score": 7.5609002113342285}, {"content": "Title: Surveillance of community-acquired viral infections due to respiratory viruses in Rhone-Alpes (France) during winter 1994 to 1995. Content: Nasal swab from patients with acute flu-like illness were evaluated for the presence of respiratory viruses in the Rhone-Alpes region of France from 1 October 1994 through 2 May 1995. The relative frequencies and seasonal distributions of the specific viruses were assessed. In addition, virus type was correlated with specific clinical signs and symptoms. During the study, 962 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network. One or more viruses were detected from 348 samples (36.1%), including 108 respiratory syncytial virus (RSV), 64 influenza virus A type H3N2, 47 influenza virus B, 64 coronavirus, 35 rhinovirus, 22 adenovirus, 5 enterovirus, and 3 parainfluenza-fluenza strains. There were 16 mixed infections. RSV infections peaked in the early winter, and influenza viruses A and B infections peaked during the late winter and early spring. There were two peaks of coronavirus infections (late fall and late winter). Other viruses were detected at lower levels throughout the study period. Patients from whom adenovirus was isolated were significantly more likely to have a fever of > 39.5 degrees C than were patients with other detectable viruses (P < 0.001). Furthermore, there was a significant correlation between influenza and cough (P < 0.01) and RSV and bronchiolitis (P < .001). Thus, the current study defined the overall and relative frequencies of respiratory virus detection from nasal swab specimens in patients with an acute flu-like illness in the Rhone-Alpes region of France during a 7-month period. Correlation with clinical signs and symptoms and provisional conclusions regarding seasonality were also determined.", "qid": 31, "docid": "2b32hntu", "rank": 54, "score": 7.546299934387207}, {"content": "Title: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan Content: Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. Methods Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray\u2122 Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. Results Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.", "qid": 31, "docid": "kxnm8l2z", "rank": 55, "score": 7.545000076293945}, {"content": "Title: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan Content: BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. METHODS: Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray&#8482; Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. RESULTS: Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.", "qid": 31, "docid": "ryojd2b3", "rank": 56, "score": 7.544999122619629}, {"content": "Title: Measuring COVID-19 and Influenza in the Real World via Person-Generated Health Data Content: Background: Since the beginning of the COVID-19 pandemic data from smartphones and connected sensors has been used to learn about symptoms presentation and management outside the clinic walls. However, reports on the validity of such data are still sparse, especially when it comes to symptom progression and relevance of wearable sensors. Objective: To understand the relevance of Person-GeneratedHealth Data (PGHD) as a means for early detection, monitoring and management of COVID-19 in everyday life. This includes quantifying prevalence and progression of symptoms from self-reports as well as changes in activity and physiological parameters continuously measured from wearable sensors, and contextualizing findings for COVID-19 patients with those from cohorts of flu patients. Design, Setting, and Participants: Retrospective digital cohort study of individuals with a self-reported positive SARS-CoV-2 or influenza test followed over the period 2019-12-02 to2020-04-27. Three cohorts were derived: Patients who self-reported being diagnosed with flu prior to the SARS-CoV-2 pandemic (N=6270, of which 1226 also contributed sensorPGHD); Patients who reported being diagnosed with flu during the SARS-CoV-2 pandemic (N=426, of which 85 also shared sensor PGHD); and patients who reported being diagnosed withCOVID-19 (N=230, of which sensor PGHD was available for 41).The cohorts were derived from a large-scale digital participatory surveillance study designed to track Influenza-like Illness(ILI) incidence and burden over time. Exposures: Self-reported demographic data, comorbidities, and symptoms experienced during a diagnosed ILI episode, including SARS-CoV-2.Physiological and behavioral parameters measured daily from commercial wearable sensors, includingResting Heart Rate (RHR), total step count, and nightly sleep hours. Main Outcomes and Measures: We investigated the percent-age of individuals experiencing symptoms of a given type (e.g.shortness of breath) across demographic groups and over time. We examined illness duration, and care seeking behavior, and how RHR, step count, and nightly sleep hours deviated from expected behavior on healthy days over the course of the infection episode. Results: Self-reported symptoms of COVID-19 present differently from flu. COVID-19 cases tended to last longer than flu(median of 12 vs. 9 days), are uniquely characterized by chest pain/pressure, shortness of breath, and anosmia. The fraction of elevated RHR measurements collected daily from commercial wearable devices rise significantly in the 2 days surrounding ILI symptoms onset, but does not appear to do so in a way specific to COVID-19. Steps lost due to COVID-19 persists for longer. Conclusion and Relevance: PGHD can be a valid source of longitudinal real world data to detect and monitor COVID-19-related symptoms and behaviors at population scale. PGHD may provide continuous, near realtime feedback to intervention effectiveness that otherwise requires waiting for symptoms to develop into contacts with the healthcare system. It has also the potential to increase pre-test probability of other downstream diagnostics. To effectively leverage PGHD for participatory surveillance it is crucial to invest in the creation of trusted, long-term communication channels with individuals through whichdata can be efficiently collected, consented, and contextualized,while protecting the privacy of individuals and ultimately facilitating the transition in and out of care.", "qid": 31, "docid": "2bz9u8k0", "rank": 57, "score": 7.532100200653076}, {"content": "Title: Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study Content: BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006\u201311; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16\u201322) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13\u201334), suggesting most influenza infections are asymptomatic. 25% (18\u201335) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10\u201326) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust.", "qid": 31, "docid": "v056i6g7", "rank": 58, "score": 7.5258002281188965}, {"content": "Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies Content: BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1\u20133) and 6 days (IQR 4\u201310) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4\u20137.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5\u201326.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.", "qid": 31, "docid": "82m3w06s", "rank": 59, "score": 7.486100196838379}, {"content": "Title: A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread Content: BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.", "qid": 31, "docid": "eiek6olk", "rank": 60, "score": 7.4704999923706055}, {"content": "Title: A Model for Characterizing Annual Flu Cases Content: Influenza outbreaks occur seasonally and peak during winter season in temperate zones of the Northern and Southern hemisphere. The occurrence and recurrence of flu epidemics has been alluded to variability in mechanisms such temperature, climate, host contact and traveling patterns [4]. This work promotes a Gaussian\u2013type regression model to study flu outbreak trends and predict new cases based on influenza\u2013like\u2013illness data for France (1985\u20132005). We show that the proposed models are appropriate descriptors of these outbreaks and can improve the surveillance of diseases such as flu. Our results show that limited data reduces our ability to predict unobserved cases. Based on laboratory surveillance data, we prototype each season according to the dominating virus (H3N2, H1N1, B) and show that high intensity outbreaks are correlated with early peak times. These findings are in accordance with the dynamics observed for influenza outbreaks in the US.", "qid": 31, "docid": "zw6qf621", "rank": 61, "score": 7.438399791717529}, {"content": "Title: Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons Content: OBJECTIVE: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS: The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children <2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS: Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children <3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children <3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS: The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses\u2014particularly in children <3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children.", "qid": 31, "docid": "g2oc32dm", "rank": 62, "score": 7.392099857330322}, {"content": "Title: Comparison of the fecal microbiota of domestic commercial meat, laboratory, companion, and shelter rabbits (Oryctolagus cuniculi) Content: BACKGROUND: Rabbits are cecotrophic, hindgut-fermenters that rely heavily on their gastrointestinal microbiota for optimal digestion of plant-based diets. Dysbiosis, caused by disruption of the gastrointestinal microbiota, is known to predispose rabbits to rabbit enteritis complex (REC), a major cause of morbidity and mortality. The objectives of this study were to describe the fecal microbiota of domestic rabbits from a variety of settings (commercial meat, companion, laboratory, and shelter) and to identify how factors such as age, season, and routine antimicrobial use affect the fecal microbiota composition. RESULTS: A total of 86 pooled commercial meat, 54 companion, 14 pooled laboratory, and 14 shelter rabbit fecal samples were evaluated using 16S rRNA gene sequencing of the V4 region. In all sample types, the predominant bacterial phylum was Firmicutes. Other commonly identified phyla (composing \u2265 1% of the total microbiota composition) were Verrucomicrobia, Proteobacteria, and Bacteroidetes. Significant differences in composition were noted between commercial, companion, laboratory, and shelter rabbit samples for proportions of Verrucomicrobia (P < 0.01), Proteobacteria (P < 0.01), and Lentisphaerae (P = 0.01) within the total microbiota. Within the commercial meat rabbit samples, significant differences between the microbiota composition of growers (n = 42) and does (n = 44) were limited to one unclassified Firmicutes (P = 0.03) and no differences were identified at the phylum level. Significant differences were present between fecal samples taken from rabbits during the summer (n = 44) compared to the winter (n = 42), with Firmicutes (P = 0.04), Verrucomicrobia (P = 0.03), Proteobacteria (P = 0.02), Deinococcus-Thermus (P = 0.04), Armatimonadates (P = 0.003), and Actinobacteria (P = 0.03) forming significantly different proportions of the microbiota. The only significant difference in composition between those farms that routinely reported antimicrobial use and those that did not was in one unclassified Bacteroidetes (P < 0.05) and no differences were identified at the phylum level. CONCLUSIONS: Rabbit husbandry and diet, in addition to season, significantly influence the fecal microbiota composition of domestic rabbits, while age of the rabbit post-weaning has minimal impact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1464-6) contains supplementary material, which is available to authorized users.", "qid": 31, "docid": "qhc8b5x1", "rank": 63, "score": 7.382699966430664}, {"content": "Title: Impacts of rapid flu clinic services at an emergency department during the pandemic flu season Content: BACKGROUND: We performed an assessment of an independent rapid flu clinic service (RFCS) unit, which was set up outside the emergency department (ED) during the 2009 H1N1 pandemic season. The unit was able to relieve the crowding of regular ambulatory and emergency services. METHODS: Between August and December 2009, a total of 6,152 patients with influenza-like illness were enrolled in this observational retrospective study. Patients with positive influenza tests were interviewed to evaluate the efficiency of RFCS. RESULTS: The mean length of stay (LOS) for the RFCS was 50 minutes, which was shorter than the LOS for ambulatory services (1 hour) and regular ED services (3.5 hours). Overall, 88% of patients were satisfied with the RFCS. Of 6,152 patients receiving flu tests, 1,235 (20%) had a positive result. Fever (odds ratio [OR], 4.28, 95% confidence interval [CI]: 3.11-5.89), fever combined with cough and sore throat (OR, 2.52; 95% CI: 2.18-2.92), fever combined with sore throat (OR, 2.42; 95% CI: 2.13-2.75), history of contacting confirmed flu patients within 7 days (OR, 2.40; 95% CI: 2.07-2.78), fever combined with cough (OR, 2.19; 95% CI: 1.92-2.47), sore throat (OR, 2.03, 95% CI: 1.79-2.30); and cough (OR, 1.91, 95% CI: 1.69-2.17) were significantly associated with positive influenza tests. CONCLUSION: Setting up the RFSC was beneficial to health care facilities during a pandemic flu season.", "qid": 31, "docid": "aqif7q3n", "rank": 64, "score": 7.358399868011475}, {"content": "Title: Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of-care test for influenza A virus detection and pandemic H1 subtyping Content: Abstract Background Influenza antigenic point-of-care (POC) tests are too insensitive for individual reliable diagnosis of influenza virus infections without additional laboratory confirmation. Molecular POC tests could be a valuable alternative. Objectives To evaluate the first influenza molecular POC test commercially available, the Cepheid Xpert Flu A Panel designed to simultaneously detect influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in-house real-time RT-PCR (qRT-PCR). Study design Clinical specimens positive for influenza virus and influenza virus isolates with different viral loads and of different type and subtype were used to determine the analytical reactivity and sensitivity. A panel of pathogen negative specimens and isolates of 19 different respiratory pathogens were used to determine the analytical specificity. Results Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009 pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of 400\u20135000 viral particles per ml. However, of most subtypes some specimens with cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with inconsistent results in the qRT-PCR due to primer or probe mismatches were not detected in the Xpert Flu A Panel. Analytical specificity was 100%. Conclusions The Xpert Flu A Panel is the first commercially available POC molecular test for detection of influenza A virus and determination of the H1 2009 subtype and is analytically reasonable sensitive compared with qRT-PCR and highly specific and therefore a welcome alternative to antigenic POC tests.", "qid": 31, "docid": "asf5c7xu", "rank": 65, "score": 7.35290002822876}, {"content": "Title: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Content: Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.", "qid": 31, "docid": "gh58t6eh", "rank": 66, "score": 7.326099872589111}, {"content": "Title: Hajj-associated infections Content: Abstract Background The Hajj is the largest annual mass gathering event in the world, thus favoring the transmission of various infections: 183 different nationalities, high temperatures, coincidence with the start of the flu season in the Northern hemisphere, a long barefoot walk, tent-type accommodation, communal toilet facilities, absence of food control, and sharing of razors. Infections are the first cause of hospital admission, which often occurs in the home country of pilgrims. Methods Literature review on PubMed from 1952 to November 2015 on the epidemiology and prevention of infections contracted during the Hajj, using the keywords \u201cHajj\u201d and \u201cinfections\u201d. Results Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj. Outbreaks of meningococcal meningitis have been reported in pilgrims and their contacts. Waterborne infections such as gastroenteritis and hepatitis A are common, despite the improvement of health conditions. Pyoderma and furuncles are also frequently observed. Recently, dengue fever, Alkhumra hemorrhagic fever, and Rift Valley fever have emerged but no case of MERS-coronavirus, appeared in Saudi Arabia in 2012, have yet been observed during the 2012\u20132014 Hajj. Conclusion Prevention is based on compulsory meningococcal vaccination, vaccination against seasonal influenza and pneumococcal infections for pilgrims at high risk of contracting the infection, and on vaccination against hepatitis A. Updating immunization for diphtheria/tetanus/poliomyelitis/pertussis and measles/mumps is also crucial and pilgrims must comply with hygiene precautions.", "qid": 31, "docid": "8sp12c7z", "rank": 67, "score": 7.322400093078613}, {"content": "Title: Social Distancing and Personal Protective Measures Decrease Influenza Morbidity and Mortality Content: Seasonal influenza (flu) is an underappreciated source of disease morbidity and mortality worldwide. While vaccination remains the cornerstone of influenza prevention, common measures practiced during the COVID-19 pandemic such as social distancing, the use of protective face masks, and frequent hand washing are rarely utilized during flu season. In this investigation, we examined the effect of these preventative measures in decreasing influenza burden this year. We examined three countries with major COVID-19 outbreaks i.e. China, Italy and the United States, and compared the flu activity this year to the average of the last 4 years (2015-2019). We found that this year in China and Italy, there was a significantly steeper decline of flu cases than average, which correlated with an increase in positive COVID-19 case reports in those countries. These \"averted\" cases can be translated into a substantial decrease in morbidity and mortality. As such, we conclude that the current COVID-19 pandemic is a reminder that behavioral measures can decrease the burden of communicable respiratory infections, and these measures should be adopted to an extent during normal influenza season.", "qid": 31, "docid": "jitmsez2", "rank": 68, "score": 7.31879997253418}, {"content": "Title: High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults Content: Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18\u201320 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point. Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers. Conclusion: IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort. This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection. However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort. If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.", "qid": 31, "docid": "msdyszr1", "rank": 69, "score": 7.298900127410889}, {"content": "Title: Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient Content: In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.", "qid": 31, "docid": "q8pagn56", "rank": 70, "score": 7.296899795532227}, {"content": "Title: Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics Content: Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it\u2019s local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summary As shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.", "qid": 31, "docid": "e8dd0bw1", "rank": 71, "score": 7.293399810791016}, {"content": "Title: The impact of media coverage on the transmission dynamics of human influenza Content: BACKGROUND: There is an urgent need to understand how the provision of information influences individual risk perception and how this in turn shapes the evolution of epidemics. Individuals are influenced by information in complex and unpredictable ways. Emerging infectious diseases, such as the recent swine flu epidemic, may be particular hotspots for a media-fueled rush to vaccination; conversely, seasonal diseases may receive little media attention, despite their high mortality rate, due to their perceived lack of newness. METHODS: We formulate a deterministic transmission and vaccination model to investigate the effects of media coverage on the transmission dynamics of influenza. The population is subdivided into different classes according to their disease status. The compartmental model includes the effect of media coverage on reporting the number of infections as well as the number of individuals successfully vaccinated. RESULTS: A threshold parameter (the basic reproductive ratio) is analytically derived and used to discuss the local stability of the disease-free steady state. The impact of costs that can be incurred, which include vaccination, education, implementation and campaigns on media coverage, are also investigated using optimal control theory. A simplified version of the model with pulse vaccination shows that the media can trigger a vaccinating panic if the vaccine is imperfect and simplified messages result in the vaccinated mixing with the infectives without regard to disease risk. CONCLUSIONS: The effects of media on an outbreak are complex. Simplified understandings of disease epidemiology, propogated through media soundbites, may make the disease significantly worse.", "qid": 31, "docid": "vg42z900", "rank": 72, "score": 7.24560022354126}, {"content": "Title: Viral Etiology of Acute Respiratory Infection in Gansu Province, China, 2011 Content: BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1\u20133 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.", "qid": 31, "docid": "yn2j21ka", "rank": 73, "score": 7.243100166320801}, {"content": "Title: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic. Content: A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "qid": 31, "docid": "28sgnyh1", "rank": 74, "score": 7.232100009918213}, {"content": "Title: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic Content: A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "qid": 31, "docid": "3p2dl8yf", "rank": 75, "score": 7.2320990562438965}, {"content": "Title: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic Content: A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "qid": 31, "docid": "ac0whd9v", "rank": 76, "score": 7.23209810256958}, {"content": "Title: How diseases rise and fall with the seasons\u2014and what it could mean for coronavirus Content: Scientists and doctors have observed for thousands of years that some diseases, such as polio and influenza, rise and fall with the seasons But why? Ongoing research in animals and humans suggests a variety of causes, including changes in the environment (like pH, temperature, and humidity) and even seasonal and daily changes to our own immune systems Figuring out those answers could one day make all the difference in minimizing the impact of infectious disease outbreaks\u2014such as coronavirus disease 2019", "qid": 31, "docid": "zespmk29", "rank": 77, "score": 7.208899974822998}, {"content": "Title: Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches Content: Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.", "qid": 31, "docid": "4i0gici7", "rank": 78, "score": 7.208399772644043}, {"content": "Title: Health Information\u2013Seeking Patterns of the General Public and Indications for Disease Surveillance: Register-Based Study Using Lyme Disease Content: BACKGROUND: People using the Internet to find information on health issues, such as specific diseases, usually start their search from a general search engine, for example, Google. Internet searches such as these may yield results and data of questionable quality and reliability. Health Library is a free-of-charge medical portal on the Internet providing medical information for the general public. Physician\u2019s Databases, an Internet evidence-based medicine source, provides medical information for health care professionals (HCPs) to support their clinical practice. Both databases are available throughout Finland, but the latter is used only by health professionals and pharmacies. Little is known about how the general public seeks medical information from medical sources on the Internet, how this behavior differs from HCPs\u2019 queries, and what causes possible differences in behavior. OBJECTIVE: The aim of our study was to evaluate how the general public\u2019s and HCPs\u2019 information-seeking trends from Internet medical databases differ seasonally and temporally. In addition, we aimed to evaluate whether the general public\u2019s information-seeking trends could be utilized for disease surveillance and whether media coverage could affect these seeking trends. METHODS: Lyme disease, serving as a well-defined disease model with distinct seasonal variation, was chosen as a case study. Two Internet medical databases, Health Library and Physician\u2019s Databases, were used. We compared the general public\u2019s article openings on Lyme disease from Health Library to HCPs\u2019 article openings on Lyme disease from Physician\u2019s Databases seasonally across Finland from 2011 to 2015. Additionally, media publications related to Lyme disease were searched from the largest and most popular media websites in Finland. RESULTS: Both databases, Health Library and Physician\u2019s Databases, show visually similar patterns in temporal variations of article openings on Lyme disease in Finland from 2011 to 2015. However, Health Library openings show not only an increasing trend over time but also greater fluctuations, especially during peak opening seasons. Outside these seasons, publications in the media coincide with Health Library article openings only occasionally. CONCLUSIONS: Lyme disease\u2013related information-seeking behaviors between the general public and HCPs from Internet medical portals share similar temporal variations, which is consistent with the trend seen in epidemiological data. Therefore, the general public\u2019s article openings could be used as a supplementary source of information for disease surveillance. The fluctuations in article openings appeared stronger among the general public, thus, suggesting that different factors such as media coverage, affect the information-seeking behaviors of the public versus professionals. However, media coverage may also have an influence on HCPs. Not every publication was associated with an increase in openings, but the higher the media coverage by some publications, the higher the general public\u2019s access to Health Library.", "qid": 31, "docid": "mtgj5vuk", "rank": 79, "score": 7.206299781799316}, {"content": "Title: The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach Content: The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states.", "qid": 31, "docid": "ysa8vb9x", "rank": 80, "score": 7.137199878692627}, {"content": "Title: Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus. Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a \"mixing vessel\" or intermediate host in the transmission of avian influenza to humans during the 1918 \"Spanish flu\" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.", "qid": 31, "docid": "tz62llbe", "rank": 81, "score": 7.079899787902832}, {"content": "Title: Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season Content: BACKGROUND: Despite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce. AIM: In this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time. METHODS: In this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY) each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap (\u2018Nowcasting\u2019). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season. RESULTS: The models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09\u20131.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, \u2018griep\u2019 (\u2018flu\u2019), having the most weight in all models. DISCUSSION: This study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.", "qid": 31, "docid": "vzly6sp7", "rank": 82, "score": 7.068999767303467}, {"content": "Title: How Should the Rehabilitation Community Prepare for 2019-nCoV? Content: With the novel coronavirus 2019 (2019-nCoV) pandemic spreading quickly in the United States and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so most of the world's population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it is currently mainly social distancing and infection control measures.", "qid": 31, "docid": "5gj4lhdj", "rank": 83, "score": 7.059700012207031}, {"content": "Title: How necessary is a fast testkit for mitigation of pandemic flu? Content: It is widely feared that a novel, highly pathogenic, human transmissible influenza virus may evolve that could cause the next global pandemic. Mitigating the spread of such an influenza pandemic would require not only the timely administration of antiviral drugs to those infected, but also the implementation of suitable intervention policies for stunting the spread of the virus. Towards this end, mathematical modelling and simulation studies are crucial as they allow us to evaluate the predicted effectiveness of the various intervention policies before enforcing them. Diagnosis plays a vital role in the overall pandemic management framework by detecting and distinguishing the pathogenic strain from the less threatening seasonal strains and other influenza-like illnesses. This allows treatment and intervention to be deployed effectively, given limited antiviral supplies and other resources. However, the time required to design a fast and accurate testkit for novel strains may limit the role of diagnosis. Herein, we aim to investigate the cost and effectiveness of different diagnostic methods using a stochastic agent-based city-scale model, and then address the issue of whether conventional testing approaches, when used with appropriate intervention policies, can be as effective as fast testkits in containing a pandemic outbreak. We found that for mitigation purposes, fast and accurate testkits are not necessary as long as sufficient medication is given, and are generally recommended only when used with extensive contact tracing and prophylaxis. Additionally, in the event of insufficient medication and fast testkits, the use of slower, conventional testkits together with proper isolation policies while waiting for the diagnostic results can be an equally effective substitute.", "qid": 31, "docid": "sfshosp0", "rank": 84, "score": 7.055099964141846}, {"content": "Title: Implications of COVID-19 Outbreak on Immune Therapies in Multiple Sclerosis Patients-Lessons Learned From SARS and MERS Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. In particular, the large number of different disease-modifying therapies (DMTs) in the treatment of neuroimmunological diseases such as multiple sclerosis poses a challenge. To a limited extent, it might be useful to transfer knowledge from previous SARS- and Middle East respiratory syndrome (MERS) coronavirus outbreaks in 2002/2003 and 2012 to the current situation. Overall, immunosuppressive therapy does neither seem to have a major impact on infection with SARS- and MERS-CoV nor does it seem to lead to a severe disease course in many cases. Considering the immunological responses against infections with novel coronaviruses in humans, interferons, glatiramer acetate, and teriflunomide appear to be safe. As lymphopenia seems to be associated with a more severe disease course, all DMTs causing lymphopenia, such as cladribine, alemtuzumab, and dimethyl fumarate, need to be reviewed more thoroughly. As they are, in general, associated with a higher risk of infection, depleting anti-CD20 antibodies may be problematic drugs. However, it has to be differentiated between the depletion phase and the phase of immune reconstitution. In summary, previous coronavirus outbreaks have not shown an increased risk for immunocompromised patients. Patients with severe neuroimmunological diseases should be kept from hasty discontinuation of immunotherapy.", "qid": 31, "docid": "a271qgvh", "rank": 85, "score": 7.049099922180176}, {"content": "Title: Implications of COVID-19 Outbreak on Immune Therapies in Multiple Sclerosis Patients\u2014Lessons Learned From SARS and MERS Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. In particular, the large number of different disease-modifying therapies (DMTs) in the treatment of neuroimmunological diseases such as multiple sclerosis poses a challenge. To a limited extent, it might be useful to transfer knowledge from previous SARS- and Middle East respiratory syndrome (MERS) coronavirus outbreaks in 2002/2003 and 2012 to the current situation. Overall, immunosuppressive therapy does neither seem to have a major impact on infection with SARS- and MERS-CoV nor does it seem to lead to a severe disease course in many cases. Considering the immunological responses against infections with novel coronaviruses in humans, interferons, glatiramer acetate, and teriflunomide appear to be safe. As lymphopenia seems to be associated with a more severe disease course, all DMTs causing lymphopenia, such as cladribine, alemtuzumab, and dimethyl fumarate, need to be reviewed more thoroughly. As they are, in general, associated with a higher risk of infection, depleting anti-CD20 antibodies may be problematic drugs. However, it has to be differentiated between the depletion phase and the phase of immune reconstitution. In summary, previous coronavirus outbreaks have not shown an increased risk for immunocompromised patients. Patients with severe neuroimmunological diseases should be kept from hasty discontinuation of immunotherapy.", "qid": 31, "docid": "p972f69v", "rank": 86, "score": 7.049098968505859}, {"content": "Title: Prevalence of Flu-like Symptoms and COVID-19 in Healthcare Workers from India Content: Background: The current COVID-19 pandemic is unprecedented. As the numbers expand exponentially, a paucity of data regarding health care workers (HCWs), who are at the forefront of this disaster, exists. Hence we decided to conduct a study amongst the HCWs to determine the prevalence and risk factor stratification. Methods: This was an online questionnaire-based survey of healthcare workers conducted at Max Super Speciality Hospital, Saket, New Delhi, India from 23rd March to 30th April 2020. Data on flu-like symptoms, travel history, posting in high-risk or low risk zones, and prophylactic drugs was collected. Results: Out of the 18000 HCWs who were approached 4403 responded and adequate data of 3667 was available for analysis. 14.7% had flu-like symptoms. 1.8% (20/1113) of the participants tested were positive for the virus. HCWs posted in the high-risk zones had more symptoms than those working in low-risk zones (169/539, 31.4% vs 679/3128, 21.7%), p<0.001; but no difference in COVID-19 positivity rates (p=0.849). Symptomatic HCWs had higher positivity (10/193, 5.2%) than the asymptomatic ones (10/920, 1.1%), p=0.001. HCQ was taken by 755/1113 (67.8%) people and 14 (1.9%) of these reported positive for the virus. Conclusion: This is the first study on healthcare workers from India to the best of our knowledge. Our findings suggest that posting in a high-risk zone with adequate PPE does not pose higher risk to the HCWs. Moreover, HCQ as a prophylactic has no use. ClinicalTrials.gov Identifier: NCT04339608.", "qid": 31, "docid": "f5sf1vqk", "rank": 87, "score": 7.023799896240234}, {"content": "Title: Prevalence of Flu-like Symptoms and COVID-19 in Healthcare Workers from India. Content: Background The current COVID-19 pandemic is unprecedented. As the numbers expand exponentially, a paucity of data regarding health care workers (HCWs), who are at the forefront of this disaster, exists. Hence we decided to conduct a study amongst the HCWs to determine the prevalence and risk factor stratification. Methods This was an online questionnaire-based survey of healthcare workers conducted at Max Super Speciality Hospital, Saket, New Delhi, India from 23rd March to 30th April 2020. Data on flu-like symptoms, travel history, posting in high-risk or low risk zones, and prophylactic drugs was collected. Results Out of the 18000 HCWs who were approached 4403 responded and adequate data of 3667 was available for analysis. 14.7% had flu-like symptoms. 1.8% (20/1113) of the participants tested were positive for the virus. HCWs posted in the high-risk zones had more symptoms than those working in low-risk zones (169/539, 31.4% vs 679/3128, 21.7%), p<0.001; but no difference in COVID-19 positivity rates (p=0.849). Symptomatic HCWs had higher positivity (10/193, 5.2%) than the asymptomatic ones (10/920, 1.1%), p=0.001. HCQ was taken by 755/1113 (67.8%) people and 14 (1.9%) of these reported positive for the virus. Conclusion This is the first study on healthcare workers from India to the best of our knowledge. Our findings suggest that posting in a high-risk zone with adequate PPE does not pose higher risk to the HCWs. Moreover, HCQ as a prophylactic has no use. ClinicalTrials.gov Identifier NCT04339608.", "qid": 31, "docid": "zdkmqqfm", "rank": 88, "score": 7.023798942565918}, {"content": "Title: Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza Content: Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.", "qid": 31, "docid": "p38x1q8s", "rank": 89, "score": 7.006100177764893}, {"content": "Title: Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study Content: BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK\u2019s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.", "qid": 31, "docid": "rgc0o2ws", "rank": 90, "score": 7.000199794769287}, {"content": "Title: Viral pathogens of acute lower respiratory tract infection in China. Content: OBJECTIVES To document the viral etiology of acute lower respiratory tract infection (ALRIs) in Chinese children. SETTING Children Hospital, Zhejiang University, China. STUDY DESIGN Cross-sectional. PARTICIPANTS 34885 children with ALRI between January 2001 to December 2006. METHODS Nasopharyngeal aspirates were collected from all subjects. Respiratory syncytial virus (RSV), adenovirus (ADV), type 1 to 3 parainfluenza viruses (PIV), and type A and B influenza virus (Flu) were detected by direct immunofluorescence. RESULTS Viruses were identified in 32.3% cases, including RSV (23.6%), PIV 3 (4.3%), Flu A (2.0%), ADV (1.7%), PIV I (0.6%), Flu B (0.2%) and PIV 2 (0.1%). RSV and PIV 3 predominated in younger children while Flu A and Flu B predominated in older children (P<0.001, respectively). PIV 1 was more prevalent in children aged 1 to 3 years. The peak frequency of RSV, PIV 3 and Flu A were in early spring, June to August, and August and September, respectively. Flu B had a peak in the winter and spring. Adenovirus infections occurred in all seasons with a relatively constant frequency. CONCLUSIONS Viruses are an important cause of ALRIs in Chinese children constituting 1/3 of total cases. RSV is the most common pathogen.", "qid": 31, "docid": "de8haxop", "rank": 91, "score": 6.986999988555908}, {"content": "Title: Are coinfections with COVID-19 and influenza low or underreported? An observational study examining current published literature including three new unpublished cases Content: As the coronavirus disease-2019 (COVID-19) pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020 to 2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, TX, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of 13 patients described therein. Three additional patients were identified from the El Paso, TX data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome. The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens.", "qid": 31, "docid": "m7qoy6yq", "rank": 92, "score": 6.97760009765625}, {"content": "Title: From \u201cA\u201dIV to \u201cZ\u201dIKV: Attacks from Emerging and Re-emerging Pathogens Content: 100 years after the infamous \u201cSpanish flu\u201d pandemic, the 2017\u20132018 flu season has been severe, with numerous infections worldwide. In between, there have been continuous, relentless attacks from (re-)emerging viruses. To fully understand viral pathogenesis and develop effective medical countermeasures, we must strengthen current surveillance and basic research efforts.", "qid": 31, "docid": "r2ys94r5", "rank": 93, "score": 6.961900234222412}, {"content": "Title: Human coronaviruses: what do they cause? Content: SARS-CoV, human coronavirus NL63 (HCoV-NL63) and HCoV-HKU1 were first described in 2003, 2004 and 2005 respectively. Nevertheless, discovery of three new human coronaviruses does not necessary represent a sudden increase in emerging infections by new coronaviruses. Only SARS-CoV has recently been introduced to the human population; the other two have been circulating in humans for a long time. HCoV-HKU1 and HCoV-NL63 are respiratory coronaviruses, are frequently found during lower and upper respiratory tract infections, have spread worldwide, and prefer the winter season. These characteristics do not differ greatly from the symptoms described for the 'old' viruses HCoV-229E and HCoV-OC43. This report presents an overview of the current knowledge of the four human coronavirus that are now circulating in the human population.", "qid": 31, "docid": "wgydshhj", "rank": 94, "score": 6.952400207519531}, {"content": "Title: The contribution of respiratory pathogens to the seasonality of NHS Direct calls Content: Summary Objectives Primary care is thought to bear half the cost of treating infections in the UK. We describe the seasonal variation in NHS Direct respiratory calls (a new source of primary care data) and estimate the contribution of specific respiratory pathogens to this variation. Methods Linear regression models were used to estimate the weekly contribution of specific respiratory pathogens to the volume of NHS Direct respiratory calls (England and Wales, 2002\u20132004, all ages and 0\u20134years). Results Annual peaks in NHS Direct cough and difficulty breathing calls occurred in late December, with peaks in \u2018cold/flu\u2019 and fever calls occurring between November and April. The main explanatory variables were influenza (estimated to account for 72.5 calls per 100,000/year; 22% of \u2018cold/flu\u2019 calls; 15% of cough; and 13% of fever) and Streptococcus pneumoniae (55.5 per 100,000; 33% of \u2018cold/flu\u2019 calls; 20% of cough; and 15% of fever (0\u20134years)). Conclusions It is estimated that respiratory viruses, notably influenza and RSV, are responsible for at least 50% of the seasonal variation in NHS Direct respiratory calls. These results provide estimates of the burden of specific respiratory diseases reported to NHS Direct, and will help interpret syndromic surveillance data used to provide early warning of rises in community morbidity.", "qid": 31, "docid": "su33vn15", "rank": 95, "score": 6.952099800109863}, {"content": "Title: Creating a comprehensive multi-tiered influenza management plan for a large healthcare system Content: ISSUE: Influenza infections affect 20% of the U.S. population, with an average of 110,000 hospitalizations and 36,000 deaths annually. The shortage of influenza vaccine for the 2004\u20132005 season brought with it the potential for an even higher rate of morbidity and mortality due to influenza. The Infection Control and Healthcare Epidemiology Consortium of a 12-hospital healthcare system located in St. Louis, Missouri, determined that a comprehensive multi-tiered influenza management plan was needed. PROJECT: A team of four infection control practitioners (ICPs) was established from three of the system's hospitals, including a large, metropolitan teaching hospital, a comprehensive pediatric hospital, and a small community hospital, along with three system-level consultants, under the advisement of their medical directors. The team developed a resource packet containing a comprehensive multi-tiered influenza management plan. The packet included a core policy, to be customized by each entity, a checklist of recommended materials to have on hand, and algorithms for influenza testing, patient placement, and healthcare worker immunization. The packet also included an admission screening tool, examples of local health department' line list reports, and educational posters to be used throughout the healthcare facilities to heighten influenza infection prevention awareness. Many of the tools have specific recommendations for different stages of the influenza season; for example, extensive use of rapid diagnostic tests is appropriate early on, but unnecessary during peak flu season when diagnosis can reliably be made based on symptoms. The packet was developed as a guide to assist ICPs in preparing for an influenza season. RESULTS: A resource packet with a comprehensive multi-tiered influenza management plan was developed for all of the system's hospitals. The packet contains information addressing the action to be taken prior to and at the early onset of the influenza season, when there is an increased level of influenza activity, and during a pandemic event. LESSONS LEARNED: Annual influenza outbreaks are a serious threat to U.S. patients. To reduce that threat, it is necessary to carefully plan and prepare for each influenza season. A resource packet with a comprehensive multi-tiered influenza management plan is a useful tool in making the necessary plans and preparations.", "qid": 31, "docid": "h2hm73u1", "rank": 96, "score": 6.9440999031066895}, {"content": "Title: Animals and coronavirus, help for African labs and a short flu season Content:", "qid": 31, "docid": "6kgliogi", "rank": 97, "score": 6.9274001121521}, {"content": "Title: Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct Content: BACKGROUND: During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach. METHODS: 33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness. RESULTS: Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere. CONCLUSIONS: Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.", "qid": 31, "docid": "k9qiwy1b", "rank": 98, "score": 6.906199932098389}, {"content": "Title: Patterns of mortality during pandemic: An example of Spanish flu pandemic of 1918 Content: Now the attention of the whole world is focused on the developing pandemic of the coronavirus infection COVID-19. This article discusses mortality patterns of the deadliest epidemic in the last 120 years \u2013 the Spanish flu pandemic of 1918. Statistical sources from Italy and the USA, published shortly after the pandemic, were analyzed. The analysis was carried out for mortality from all causes, since in this case inaccuracies associated with establishing the causes of death are minimized. Despite the fact that the first cases of the Spanish flu appeared in the United States as early as March 1918, this first wave of epidemic practically did not affect the total mortality rate. The main peak of mortality in 1918 occurred in October 1918 both in the USA and Italy, with a gradual decrease in mortality over several months. Analysis of age-specific mortality demonstrates a significant increase in mortality at middle ages (20\u201350 years) in 1918 compared with 1917. Analysis of mortality trends using the method of latent variables shows a significant increase in the background mortality factor in 1918, which turned out to be higher for Italy than the mortality losses during the Second World War. The Spanish flu pandemic differs from the current coronavirus pandemic, because of significant increase in mortality of middle-aged people, while the COVID-19 pandemic causes a more marked increase in mortality among the elderly. With this, the COVID-19 pandemic is more like the recent flu epidemics than the earlier Spanish flu pandemic.", "qid": 31, "docid": "1ca2rrrz", "rank": 99, "score": 6.877500057220459}, {"content": "Title: Towards a data-driven characterization of behavioral changes induced by the seasonal flu Content: In this work, we aim to determine the main factors driving self-initiated behavioral changes during the seasonal flu. To this end, we designed and deployed a questionnaire via Influweb, a Web platform for participatory surveillance in Italy, during the 2017 \u2212 18 and 2018 \u2212 19 seasons. We collected 599 surveys completed by 434 users. The data provide socio-demographic information, level of concerns about the flu, past experience with illnesses, and the type of behavioral changes voluntarily implemented by each participant. We describe each response with a set of features and divide them in three target categories. These describe those that report i) no (26%), ii) only moderately (36%), iii) significant (38%) changes in behaviors. In these settings, we adopt machine learning algorithms to investigate the extent to which target variables can be predicted by looking only at the set of features. Notably, 66% of the samples in the category describing more significant changes in behaviors are correctly classified through Gradient Boosted Trees. Furthermore, we investigate the importance of each feature in the classification task and uncover complex relationships between individuals\u2019 characteristics and their attitude towards behavioral change. We find that intensity, recency of past illnesses, perceived susceptibility to and perceived severity of an infection are the most significant features in the classification task and are associated to significant changes in behaviors. Overall, the research contributes to the small set of empirical studies devoted to the data-driven characterization of behavioral changes induced by infectious diseases.", "qid": 31, "docid": "4d9ct9a1", "rank": 100, "score": 6.870500087738037}]}
{"query": "Does SARS-CoV-2 have any subtypes, and if so what are they?", "hits": [{"content": "Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "qid": 32, "docid": "ugkxxaeb", "rank": 1, "score": 12.04069995880127}, {"content": "Title: Is SARS-CoV-2 Vertically Transmitted? Content: At the end of 2019, in Wuhan (China), the onset of a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed. The disease, named COVID-19, has a wide spectrum of clinical presentations, ranging from asymptomatic or mild to critical, and for some patients the disease is even fatal. Apparently, being a child or being pregnant does not represent an additional risk for adverse outcomes. The purpose of this mini-review was to investigate what is in the scientific literature, so far, in regard to vertical transmission of SARS-CoV-2. Data were obtained independently by the two authors, who carried out a systematic search in the PubMed, Embase, LILACS, Cochrane, Scopus and SciELO databases using the Medical Subject Heading terms \u201ccoronavirus,\u201d \u201cCOVID-19,\u201d and \u201cvertical transmission.\u201d Few studies about the vertical transmission of SARS-CoV-2 are found in the literature. In all case reports and case series, the mothers' infection occurred in the third trimester of pregnancy, there were no maternal deaths, and most neonates had a favorable clinical course. The virus was not detected in the neonate nasopharyngeal swab samples at birth, in the placenta, in the umbilical cord, in the amniotic fluid, in the breast milk or in the maternal vaginal swab samples in any of these articles. Only three papers reported neonatal SARS-CoV-2 infection, but there is a bias that positive pharyngeal swab samples were collected at 36 h and on the 2nd, 4th, and 17th days of life. The possibility of intrauterine infection has been based mainly on the detection of IgM and IL-6 in the neonates' serum. In conclusion, to date, no convincing evidence has been found for vertical transmission of SARS-CoV-2.", "qid": 32, "docid": "r7z0nxex", "rank": 2, "score": 11.27970027923584}, {"content": "Title: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization Content: We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain [1] project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM and via an interactive website at https://covid19-ism.coe.drexel.edu/. Author Summary The novel coronavirus responsible for COVID-19, SARS-CoV-2, expanded to reportedly 8.7 million confirmed cases worldwide by June 21, 2020. The global SARS-CoV-2 pandemic highlights the importance of tracking viral transmission dynamics in real-time. Through June 2020, researchers have obtained genetic sequences of SARS-CoV-2 from over 47,000 samples from infected individuals worldwide. Since the virus readily mutates, each sequence of an infected individual contains useful information linked to the individual\u2019s exposure location and sample date. But, there are over 30,000 bases in the full SARS-CoV-2 genome\u2014so tracking genetic variants on a whole-sequence basis becomes unwieldy. We describe a method to instead efficiently identify and label genetic variants, or \u201csubtypes\u201d of SARS-CoV-2. Applying this method results in a compact, 11 base-long compressed label, called an Informative Subtype Marker or \u201cISM\u201d. We define viral subtypes for each ISM, and show how regional distribution of subtypes track the progress of the pandemic. Major findings include (1) covarying nucleotides with the spike protein which has spread rapidly and (2) tracking emergence of a local subtype across the United States connected to Asia and distinct from the outbreak in New York, which is found to be connected to Europe.", "qid": 32, "docid": "9siu7wgs", "rank": 3, "score": 10.865099906921387}, {"content": "Title: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? Content: In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus.", "qid": 32, "docid": "sphwclzs", "rank": 4, "score": 10.784099578857422}, {"content": "Title: Podcast: Beating a killer coronavirus Content: As COVID-19 continues to spread, so does the effort to find treatment and vaccinations against SARS-CoV-2, the coronavirus that causes the disease Around the world, scientists are working nonstop on therapies they hope will stem the loss of life during this pandemic while trying to set us up to prevent future outbreaks What\u2019s not clear is which of these treatments will work Much about SARS-CoV-2 remains unknown In this episode of Stereo Chemistry, we dig into the efforts to beat the novel coronavirus and why in some cases it\u2019s like throwing spaghetti against the wall to see what sticks Learn more at http://cenm ag/coronapodcast", "qid": 32, "docid": "m5brxspf", "rank": 5, "score": 10.633000373840332}, {"content": "Title: Understanding Coronavirus Content: Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience", "qid": 32, "docid": "hmvo5b0q", "rank": 6, "score": 10.20419979095459}, {"content": "Title: The Coronavirus Pandemic: What Does the Evidence Show? Content: Coronavirus disease 2019 (COVID-19) is a newly emerged disease that has become a global public health concern as it rapidly spread around the world. The etiologic agent responsible for this disease has been named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses as it shows similar genomic features to that of SARS-CoV which caused a pandemic in 2002. This disease first appeared in Hubei province of China and it follows human-to-human transmission but the path this virus took to set up human infection remains a mystery. By 17 April 2020, globally there have been 2,074,529 confirmed cases with 139,378 deaths because of COVID-19. SARS-CoV-2 shows several similarities with SARS?CoV, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) with its clinical presentations. This can vary from asymptomatic infection to severe disease and mortality. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) screening is considered as the standard laboratory test for the diagnosis of COVID-19. There is no proven antiviral agent against SARS-CoV-2 so the treatment for COVID-19 is symptomatic, aiming for the management of the symptoms and prevention of the complications. The outbreak of COVID-19 has led to the implementation of extraordinary public health measures throughout the world. Numerous antiviral compounds used to treat other infections are being clinically researched to find possible treatment. Similarly, the traditional public health outbreak response strategy of isolation, quarantine, social distancing and community containment has been implemented in multiple countries and has played an important role in the prevention of new outbreaks. This review aims to enhance our understanding of COVID 19. Keywords: Coronavirus disease 2019; COVID-19; SARS-CoV-2; novel coronavirus 2019; severe acute respiratory syndrome-2.", "qid": 32, "docid": "k6hh7yft", "rank": 7, "score": 10.1274995803833}, {"content": "Title: In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek\u2019s own, and he does not in any way speak for his employer Content: Let\u2019s take inventory on the therapies that are being developed for the coronavirus epidemic Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they\u2019re making all their Covid-19 content free to all readers during this crisis I\u2019d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons The Biocentury list doesn\u2019t cover these, but here\u2019s an article at Nature Biotechnology that goes into detail Clinical trials are a huge time sink \u2013 they sort of have to be, in most cases, if they\u2019re going to be any good \u2013 and if you\u2019ve already done all that stuff it\u2019s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right This has been in development for a few years as an RNA virus therapy \u2013 it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit The compound is a prodrug \u2013 that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524 It mechanism of action is to get incorporated into viral RNA, since it\u2019s taken up by RNA polymerase and it largely seems to evade proofreading This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited", "qid": 32, "docid": "ol0bj3hs", "rank": 8, "score": 9.93120002746582}, {"content": "Title: In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03 Content: The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.", "qid": 32, "docid": "023h20vk", "rank": 9, "score": 9.828399658203125}, {"content": "Title: A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity? Content: The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes.", "qid": 32, "docid": "1sbnewog", "rank": 10, "score": 9.812700271606445}, {"content": "Title: Complications and outcomes of SARS-CoV-2 in pregnancy: where and what is the evidence? Content: OBJECTIVES: To add to the growing evidence on SARS-CoV-2 infection during pregnancy, so as to better inform clinical decision making and optimize patient outcomes. METHODS: A systematic search of relevant databases was perfomed on 25 March 2020 and a repeat search, on 10 April 2020. Reports of pregnant patients with SARS-CoV-2 infection at any time during their pregnancy were reviewed and summarized . RESULTS: We summarized the outcomes of a total of 155 pregnant women and 118 neonates. The evidence suggests a similar rate of severe COVID-19 cases in pregnant women and the general population. The frequency of cesarean deliveries is high, against guidelines recommendations. CONCLUSION: Limited data on COVID-19 during preganacy, associated with a wide variation in the methodology make accurate data interpretation difficult.", "qid": 32, "docid": "3mriioxy", "rank": 11, "score": 9.799500465393066}, {"content": "Title: Complications and outcomes of SARS-CoV-2 in pregnancy: where and what is the evidence? Content: OBJECTIVES To add to the growing evidence on SARS-CoV-2 infection during pregnancy, so as to better inform clinical decision making and optimize patient outcomes. METHODS A systematic search of relevant databases was perfomed on 25 March 2020 and a repeat search, on 10 April 2020. Reports of pregnant patients with SARS-CoV-2 infection at any time during their pregnancy were reviewed and summarized . RESULTS We summarized the outcomes of a total of 155 pregnant women and 118 neonates. The evidence suggests a similar rate of severe COVID-19 cases in pregnant women and the general population. The frequency of cesarean deliveries is high, against guidelines recommendations. CONCLUSION Limited data on COVID-19 during preganacy, associated with a wide variation in the methodology make accurate data interpretation difficult.", "qid": 32, "docid": "be5m8j6u", "rank": 12, "score": 9.79949951171875}, {"content": "Title: What we know about the novel coronavirus\u2019s proteins Content: Scientists across the globe are gunning to understand the novel coronavirus, called SARS-CoV-2, and what makes it so contagious and deadly Several members of the coronavirus family infect humans: four cause the common cold, and two\u2014SARS-CoV and MERS-CoV\u2014have triggered dangerous epidemics The novel coronavirus\u2019s closest kin is SARS-CoV, which jumped species from bats to civets to humans to cause the severe acute respiratory syndrome (SARS) epidemic of 2002\u20133 That SARS outbreak infected just over 8,000 people The current coronavirus pandemic has infected more than 2 million people and killed more than 130,000 as of April 15, according to data from Johns Hopkins University \u201cFrom a molecular perspective, figuring out why the virus is so much more transmissible than past viruses is where we should be looking right now,\u201d says Robert Kirchdoerfer, a structural biologist at the University of Wisconsin\u2013Madison who studies how coronaviruses fuse with host cells While people infected", "qid": 32, "docid": "to4b993l", "rank": 13, "score": 9.79740047454834}, {"content": "Title: Are your cash-flow tools recession ready? Content: Abstract In good times like those most businesses have enjoyed for the past decade, business owners have typically watched their income statements with pleasure, as year-to-year performance gains have fattened their dividend payouts and increased the valuation of the companies they own and run. All too often in such times, scant attention is paid to what\u2019s between the top line and the bottom line of the income statement. Worse, most business owners, in my experience, give little more than a cursory nod to the balance sheet. Why does this matter? When a recession lands on their doorstep with a sudden thud, as it apparently just has, many of these same people will find themselves having sailed too close to the wind, with cash running out and a dearth of tools to help them weather the storm and understand what has gone wrong. But it need not be so, for there are four simple tools to help any business owner answer these four important questions: (1) Where is cash going in my business, and where is it coming from? (2) To what extent are my profit margins improving or declining, and why? (3) To what extent am I effectively managing the cash-flow relationships with my customers and my suppliers? (4) What, if anything, can I do to better manage the cash that flows into and out of my business? If your business is threatened by the COVID-19 pandemic, here are some tools to help it survive.", "qid": 32, "docid": "if4w9vg4", "rank": 14, "score": 9.784799575805664}, {"content": "Title: GPS Tracking App for Police to Track Ambulances Carrying COVID-19 Patients for Ensuring Safe Distancing Content: The outbreak of the SARS-CoV-2 virus is causing loss of lives and property all over the world. There have been more than 2.1 million cases of COVID-19 with a death of more than 1.2 lakh patients worldwide and the numbers are still rising. The virus spreads rapidly by the droplets coming out from the nose and mouth of an infected person (Sandoiu in Why does SARS-CoV-2 spread so easily? Medical news today, 2020 https://www.medicalnewstoday.com/articles/why-does-sars-cov-2-spread-so-easily). In this situation, proper quarantining and monitoring of the already infected patients are very essential. In cases where patients need to be transferred to different locations by ambulances, monitoring of these ambulances by the traffic police can help to ensure distancing and faster movement of the vehicle inside the city. This paper presents the development of a Real-time Global Positioning System-based tracking app for the ambulances carrying COVID-19 patients which would help traffic police to ensure distancing the patients from the public.", "qid": 32, "docid": "ek1m4yiy", "rank": 15, "score": 9.777799606323242}, {"content": "Title: Aerosol generating procedures and infective risk to healthcare workers: SARS-CoV-2 \u2013 the limits of the evidence Content: The transmission behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately is necessary that we establish whether aerosol generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider what risk procedures would have of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding aerosol generating procedures and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure what risk they are putting themselves in when offering these procedures. This review aimed to summarise the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.", "qid": 32, "docid": "t2j7tq92", "rank": 16, "score": 9.707099914550781}, {"content": "Title: Aerosol generating procedures and infective risk to healthcare workers: SARS-CoV-2 - the limits of the evidence Content: The transmission behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately is necessary that we establish whether aerosol generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider what risk procedures would have of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding aerosol generating procedures and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure what risk they are putting themselves in when offering these procedures. This review aimed to summarise the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.", "qid": 32, "docid": "vklc2ocs", "rank": 17, "score": 9.707098960876465}, {"content": "Title: Ultraviolet irradiation doses for coronavirus inactivation \u2013 review and analysis of coronavirus photoinactivation studies Content: Background: To slow the increasing global spread of the SARS-CoV-2 virus, appropriate disinfection techniques are required. Ultraviolet radiation (UV) has a well-known antiviral effect, but measurements on the radiation dose necessary to inactivate SARS-CoV-2 have not been published so far. Methods: Coronavirus inactivation experiments with ultraviolet light performed in the past were evaluated to determine the UV radiation dose required for a 90% virus reduction. This analysis is based on the fact that all coronaviruses have a similar structure and similar RNA strand length. Results: The available data reveals large variations, which are apparently not caused by the coronaviruses but by the experimental conditions selected. If these are excluded as far as possible, it appears that coronaviruses are very UV sensitive. The upper limit determined for the log-reduction dose (90% reduction) is approximately 10.6 mJ/cm(2) (median), while the true value is probably only 3.7 mJ/cm(2) (median). Conclusion: Since coronaviruses do not differ structurally to any great exent, the SARS-CoV-2 virus \u2013 as well as possible future mutations \u2013 will very likely be highly UV sensitive, so that common UV disinfection procedures will inactivate the new SARS-CoV-2 virus without any further modification.", "qid": 32, "docid": "kpz0o1ag", "rank": 18, "score": 9.64109992980957}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus Elicits a Weak Interferon Response Compared to Traditional Interferon-Inducing Viruses Content: The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-\u03b1, -\u03b2 and -\u03b3 compared to VSV and NDV. Characterization of the profile of IFN-\u03b1 subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-\u03b12 and \u22126 subtypes were higher compared to other IFN-\u03b1 subtypes namely, IFN-\u03b15, \u22128, \u221210, \u221213/1, \u221217, and \u221221. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.", "qid": 32, "docid": "zr495eff", "rank": 19, "score": 9.617400169372559}, {"content": "Title: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Content: Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any \u201dnormal\u201d post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.", "qid": 32, "docid": "iwkuwnun", "rank": 20, "score": 9.521400451660156}, {"content": "Title: What\u2019s new in the renin-angiotensin system?: Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus Content: Cellular entry of enveloped viruses is often dependent on attachment proteins expressed on the host cell surface. Viral envelope proteins bind these receptors, and, in an incompletely understood process, facilitate fusion of the cellular and viral membranes so as to introduce the viral core into the cytoplasm. Only a small fraction of viral receptors have been identified so far. Recently, a novel coronavirus was identified as the etiological agent of severe acute respiratory syndrome (SARS). The fusion protein gene of SARS coronavirus (SARS-CoV) was cloned and characterized, and shortly thereafter, angiotensin-converting enzyme 2 (ACE2) was shown to be its functional receptor. Identification of ACE2 as a receptor for SARS-CoV will likely contribute to the development of antivirals and vaccines. It may also contribute to the development of additional animal models for studying SARS pathogenesis, and could help identify the animal reservoir of SARS-CoV.", "qid": 32, "docid": "d11ua0oh", "rank": 21, "score": 9.408599853515625}, {"content": "Title: Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M. Content: The severe acute respiratory syndrome coronavirus (SARS-CoV) open reading frame 3a protein has recently been shown to be a structural protein. The protein is encoded by one of the so-called group-specific genes and has no sequence homology with any of the known structural or group-specific proteins of coronaviruses. It does, however, have several similarities to the coronavirus M proteins; (i) they are triple membrane spanning with the same topology, (ii) they have similar intracellular localizations (predominantly Golgi), (iii) both are viral structural proteins, and (iv) they appear to interact with the E and S proteins, as well as with each other. The M protein plays a crucial role in coronavirus assembly and is glycosylated in all coronaviruses, either by N-linked or by O-linked oligosaccharides. The conserved glycosylation of the coronavirus M proteins and the resemblance of the 3a protein to them led us to investigate the glycosylation of these two SARS-CoV membrane proteins. The proteins were expressed separately using the vaccinia virus T7 expression system, followed by metabolic labeling. Pulse-chase analysis showed that both proteins were modified, although in different ways. While the M protein acquired cotranslationally oligosaccharides that could be removed by PNGaseF, the 3a protein acquired its modifications posttranslationally, and they were not sensitive to the N-glycosidase enzyme. The SARS-CoV 3a protein, however, was demonstrated to contain sialic acids, indicating the presence of oligosaccharides. O-glycosylation of the 3a protein was indeed confirmed using an in situ O-glycosylation assay of endoplasmic reticulum-retained mutants. In addition, we showed that substitution of serine and threonine residues in the ectodomain of the 3a protein abolished the addition of the O-linked sugars. Thus, the SARS-CoV 3a protein is an O-glycosylated glycoprotein, like the group 2 coronavirus M proteins but unlike the SARS-CoV M protein, which is N glycosylated.", "qid": 32, "docid": "d56ed4hw", "rank": 22, "score": 9.408100128173828}, {"content": "Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "qid": 32, "docid": "b6aeu1ph", "rank": 23, "score": 9.34749984741211}, {"content": "Title: The global population of SARS-CoV-2 is composed of six major subtypes Content: The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.", "qid": 32, "docid": "h0q93in1", "rank": 24, "score": 9.298199653625488}, {"content": "Title: What's the plan? The unique challenges facing the home and community care sector in preparing for a pandemic. Content: Recent experience with the outbreak of severe acute respiratory syndrome (SARS) in Canada and the global threat of the H5N1 virus (avian \"flu\") have increased the appetite for and urgency of pandemic planning as a policy issue. The healthcare setting is one of the most important areas to prepare for such an event, and it is crucial that discussions around doing so include all settings in which care is delivered. As the home and community care sector is increasingly utilized and likely to be relied upon even more during a pandemic, addressing the challenges to occupational health and safety uniquely faced by this sector will be vitally important to the entire health system. A pandemic plan that does not consider healthcare outside of the institutional setting is incomplete and will be likely to fail. This commentary outlines the challenges to providing care in the home and community that must be considered in any plan designed to deal with a pandemic on a system-wide level.", "qid": 32, "docid": "yifhgoal", "rank": 25, "score": 9.280200004577637}, {"content": "Title: Does SARS-CoV-2 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets.", "qid": 32, "docid": "mcf0zvaf", "rank": 26, "score": 9.202300071716309}, {"content": "Title: Does SARS\u2010CoV\u20102 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS\u2010CoV\u20102) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS\u2010CoV\u20102 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS\u2010CoV\u20102, severe acute respiratory syndrome coronavirus (SARS\u2010CoV), and middle east respiratory syndrome coronavirus (MERS\u2010CoV), highlighting the need for larger and well\u2010annotated datasets.", "qid": 32, "docid": "p7ifetgw", "rank": 27, "score": 9.202299118041992}, {"content": "Title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization Content: STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? SUMMARY ANSWER ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization. WHAT IS KNOWN ALREADY ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. STUDY DESIGN, SIZE, DURATION Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression. MAIN RESULTS AND THE ROLE OF CHANCE In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss. STUDY FUNDINGS/COMPETING INTEREST(S) This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.", "qid": 32, "docid": "0xyrmk5a", "rank": 28, "score": 9.189599990844727}, {"content": "Title: Mutations strengthened SARS-CoV-2 infectivity Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.", "qid": 32, "docid": "8s8gezpz", "rank": 29, "score": 9.17870044708252}, {"content": "Title: Mutations on COVID-19 diagnostic targets Content: Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-2 has the most devastating mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been unfortunately used by countries around the world to diagnose COVID-19. Our findings explain what has seriously gone wrong with a specific diagnostic reagent made in China. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation ratio and mutation $h$-index of all SARS-CoV genes, indicating that the N gene is the most non-conservative gene in the SARS-CoV-2 genome. Our findings enable researchers to target the most conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, preventive vaccines, and therapeutic medicines.", "qid": 32, "docid": "8l7hrany", "rank": 30, "score": 9.1003999710083}, {"content": "Title: Meaning of dangerous goods Content: The parties to a contract for the carriage of goods by sea, whether this is embodied in a bill of lading or one of the standard charterparty forms, customarily negotiate its terms against a background of both commercial and legal considerations. The parties\u2019 respective liability for risks to which the vessel and its cargo might be exposed during the course of the contracted voyage will be of paramount importance. Should they arise, the potential risks might expose the parties, through their insurance, to expensive damage claims. Therefore, the description of the cargo for shipment is one of the crucially important components of the negotiations between the parties to any shipping contract.(1) This requirement becomes especially relevant when it has been estimated that more than 50% of the cargoes transported by sea today may be regarded as dangerous, hazardous, and/or harmful and need to be handled with special care. As a result, a shipper does not have unlimited freedom as to what he may transport by sea. Restrictions on goods which a charterer or shipper may ship are imposed by law, the terms of the contract and statutes. These restrictions are commonly elided into a general proposition that a person sending goods by sea must not ship dangerous goods. Yet it is the case that dangerous goods are often shipped and legitimately so; and the carrier should discharge his normal duties in respect of whatever cargo he has agreed to carry. The real issues, therefore, are to identify what risks are involved in the carriage of the cargo in question, how these risks are allocated between the parties and what the consequences of shipping dangerous goods are.(2)", "qid": 32, "docid": "b426t461", "rank": 31, "score": 9.088000297546387}, {"content": "Title: BCG is a good immunotherapeutic agent for viral and autoimmune diseases: Is it a new weapon against coronavirus (COVID-19)? Content: Now nearly a century old, the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine is used routinely in humans for the prophylaxis of tuberculosis and to clear up leprosy. As the immune response to the vaccine shows some degree of cross-antigenicity, the vaccine also affects a level of resistance to a range of unrelated diseases and pathogens. Clinical studies data have shown that the BCG vaccine has effects on autoimmune and inflammatory diseases. Although the vaccine does not possess any inherent antiviral activity, it engages in the host immune system such that many types of viral infections are considerably reduced. Hence, we expect that the frequency and severity of many microbial diseases, including COVID-19, will be lower in counties in which mass BCG vaccination programs are implemented. So the BCG vaccine may prove useful in the coming months especially in countries where already have mass BCG vaccination, as the COVID-19 pandemic has placed an unprecedented strain on health services across the world. Currently, countless front-line healthcare staff is in immediate danger of exposure to the SARS-CoV-2 virus. Furthermore, as oral zinc sulfate as immunomodulator has proved an effective means to treat various viral diseases (including viral warts and herpes), parasitic infections, and diseases with autoimmune reactions such as Behcet\u2019s disease and recurrent aphthous stomatitis, it could be employed in combination with the BCG vaccine to enhance the immunological functions of patients with COVID-19. So BCG immunotherapy combined with oral zinc sulfate will be encouraging protective programs in societies where coronavirus is going to spread.", "qid": 32, "docid": "ko11gg2o", "rank": 32, "score": 8.962900161743164}, {"content": "Title: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Content: Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.", "qid": 32, "docid": "k3bkgf1g", "rank": 33, "score": 8.94729995727539}, {"content": "Title: Coronavirus in pregnancy. What we know so far? Content: Coronaviruses are a group of viruses which, even if they are affecting mainly mammals and birds, could be transmitted to humans, generating common cold The new virus strain is named SARS-CoV-2 and has 85% sequence similarity to SARS-CoV Until now, it has caused more than 100 000 confirmed cases of infection and almost 5000 deaths, having a mortality rate of 4% All information (symptoms, signs, management, complications) are taken from the other pandemic infections (SARS, MERS) Information about viral infection concerning pregnant women are limited and are common to other SARS infections There are very few cases of pregnant patients infected with SARS-CoV-2 and studies are ongoing", "qid": 32, "docid": "d3yt1xa8", "rank": 34, "score": 8.944299697875977}, {"content": "Title: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Content: Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.", "qid": 32, "docid": "c5be70t6", "rank": 35, "score": 8.930999755859375}, {"content": "Title: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Content: Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.", "qid": 32, "docid": "gh58t6eh", "rank": 36, "score": 8.921600341796875}, {"content": "Title: SARS-CoV-2, COVID-19, skin and immunology - what do we know so far? Content: The pandemic condition Coronavirus-disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2 positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial and maculopapular eruptions as well as livedo, necrosis and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical and histologic features of virus- as well as drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.", "qid": 32, "docid": "t8pltw5x", "rank": 37, "score": 8.814499855041504}, {"content": "Title: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? Content: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. SUMMARY: Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.", "qid": 32, "docid": "pbuevs5v", "rank": 38, "score": 8.769200325012207}, {"content": "Title: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? Content: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.", "qid": 32, "docid": "q5qkqipv", "rank": 39, "score": 8.76919937133789}, {"content": "Title: Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection Content: Recent studies have reported that COVID-19 patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Lung cancer patients in each age stage, subtype, and pathological stage are susceptible to SARS-CoV-2 infection, except for the primitive subtype of LUSC. LUAD patients are more susceptible to SARS-CoV-2 infection than LUSC patients. The findings are unanimous on tissue expression in gene and protein levels.", "qid": 32, "docid": "5izpb5dm", "rank": 40, "score": 8.759300231933594}, {"content": "Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 32, "docid": "rs79r7kc", "rank": 41, "score": 8.758299827575684}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 32, "docid": "rsz7ch2a", "rank": 42, "score": 8.758298873901367}, {"content": "Title: Host Immune Response and Immunobiology of Human SARS-CoV-2 Infection Content: One of the most serious viral outbreaks of the decade, infecting humans, originated from the city of Wuhan, China, by the end of December 2019, has left the world shaken up. It is the successor infection of severe acute respiratory syndrome coronavirus (SARS-CoV) named as SARS-CoV-2 causing a disease called as COVID-19 (Coronavirus disease-19). Being one of the most severe diseases in terms of transmission, this disease agitates the immune system of an individual quite disturbingly which at times leads to death, which is why it has become the need of the hour to step forward to extensively involve in understanding the genetics, pathogenesis, and immunopathology of SARS-CoV-2 in order to design drugs to treat or to design a vaccine to prevent. In this chapter, we have tried to review and summarize the studies done so far to understand the host\u2013pathogen relationship and the host immune response during COVID-19 infection. One of the recent developments regarding the understanding of SARS-CoV-2 infection is the mechanism of immune evasion involved during the pathogenesis and cytokine storm syndrome during infection in the patient against which a drug called as Hydroxychloroquine has been designed. Comprehensively, we have tried to give an immunological insight into the SARS-CoV-2 infection in order to understand the possible outcome for any therapeutic advancement.", "qid": 32, "docid": "bwxktvsz", "rank": 43, "score": 8.741399765014648}, {"content": "Title: Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients Content: Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic", "qid": 32, "docid": "wxyhc30h", "rank": 44, "score": 8.739999771118164}, {"content": "Title: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes Content: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it\u2019s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven\u2019t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don\u2019t yet know what the real-life significance of this variation is, but it\u2019s possible that these variants decrease the protein\u2019s ability to interact with the SARS-CoV-2 virus, thus decreasing the person\u2019s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.", "qid": 32, "docid": "p7drekee", "rank": 45, "score": 8.737700462341309}, {"content": "Title: A generalized overview of SARS-COV-2: Where does the current knowledge stand? Content: The novel coronavirus known to have brought the world to a standstill is responsible for many deaths throughout the globe as of now. The causative agent (SARS-CoV-2) for coronavirus disease 2019 (COVID-19) has been recognized as a zoonotic transfer. Although, the medium of animal-human transmission is still unknown, bats maybe a potential reservoir of this novel strain. Due to its high rate of transmission the most favorable way of limiting the outbreak\u2019s extent is by early diagnosis followed by isolation of the infected individuals. So far, the most widely used diagnosis methods are RT-qPCR which detects specific sequences of the viral RNA. Some other methods include serological tests and the recently introduced CRISPR-CAS-12 based assays. As of now, no specific therapeutic treatments are known for COVID-19 however the use of some broad-spectrum antiviral drugs and convalescent plasma therapy have demonstrated positive outcomes. Apart from these treatments, vaccine development for SARS-CoV-2 is also in progress by 17 known companies. This article provides a comprehensive insight on the recently emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) including its origin, transmission mechanism, pathophysiology and updated treatment methods.", "qid": 32, "docid": "41rsi8ce", "rank": 46, "score": 8.730500221252441}, {"content": "Title: SARS-CoV-2 and human milk: what is the evidence? Content: The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities have rapidly engaged to find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are possible. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding. There is a single study providing some evidence of vertical transmission of human coronavirus 229E, a single study evaluating presence of SARS-CoV in human milk (it was negative), and no published data on MERS-CoV and human milk. There are 9 case studies of human milk tested for SARS-CoV-2; none detected the virus. Importantly, none of the published studies on coronaviruses and human milk report validation of their analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.", "qid": 32, "docid": "nlq5755b", "rank": 47, "score": 8.719499588012695}, {"content": "Title: No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2 Content: The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that some lineages of SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible candidate mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we developed a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a carefully curated set of recurrent mutations identified within a dataset of over 23,000 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent SARS-CoV-2 mutations currently in circulation appear to be evolutionary neutral. Recurrent mutations also seem primarily induced by the human immune system via host RNA editing, rather than being signatures of adaption to the novel human host. We find no evidence at this stage for the emergence of more transmissible lineages of SARS-CoV-2 due to recurrent mutations.", "qid": 32, "docid": "a51vkiei", "rank": 48, "score": 8.718700408935547}, {"content": "Title: Replication of SARS-CoV-2 in human respiratory epithelium. Content: Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there are also a plethora of animal coronaviruses, which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002 SARS-CoV emerged, to rapidly disappear in May 2003. In 2012 MERS-CoV was identified as a possible threat to humans, but its pandemic potential so far is minimal, as the human-to-human transmission is ineffective. The end of 2019 brought us information about the SARS-CoV-2 emergence, and the virus rapidly spread in 2020 causing an unprecedented pandemic.At present, the studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for the understanding of virus biology and evolution.Here we show that fully differentiated human airway epithelium cultures constitute an excellent model to study the infection with the novel human coronavirus SARS-CoV-2. We observed an efficient replication of the virus in the tissue, with the maximal replication at 2 days post-infection. The virus replicated in ciliated cells and was released apically.IMPORTANCE SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2.", "qid": 32, "docid": "4v42ezk8", "rank": 49, "score": 8.705900192260742}, {"content": "Title: Replication of SARS-CoV-2 in human respiratory epithelium Content: Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there are also a plethora of animal coronaviruses, which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002 SARS-CoV emerged, to rapidly disappear in May 2003. In 2012 MERS-CoV was identified as a possible threat to humans, but its pandemic potential so far is minimal, as the human-to-human transmission is ineffective. The end of 2019 brought us information about the SARS-CoV-2 emergence, and the virus rapidly spread in 2020 causing an unprecedented pandemic.At present, the studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for the understanding of virus biology and evolution.Here we show that fully differentiated human airway epithelium cultures constitute an excellent model to study the infection with the novel human coronavirus SARS-CoV-2. We observed an efficient replication of the virus in the tissue, with the maximal replication at 2 days post-infection. The virus replicated in ciliated cells and was released apically.IMPORTANCE SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2.", "qid": 32, "docid": "598n91gb", "rank": 50, "score": 8.705899238586426}, {"content": "Title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models Content: Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized replication competent SARS-CoV-2 with exceptional potency as measured by two different assays. There was no enhancement of pseudovirus infection in cells expressing Fc\u03b3 receptors at any concentration. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 potently neutralized mouse ACE2 adapted SARS-CoV-2 in wild type BALB/c mice and native virus in hACE2 expressing transgenic mice. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.", "qid": 32, "docid": "ycuiso0g", "rank": 51, "score": 8.698599815368652}, {"content": "Title: [What is the origin of SARS-CoV-2?] Content: Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.", "qid": 32, "docid": "dv9m19yk", "rank": 52, "score": 8.683500289916992}, {"content": "Title: Enfermedad pulmonar obstructiva cr\u00f3nica e infecci\u00f3n por SARS-CoV-2. \u00bfQu\u00e9 sabemos hasta ahora?/ Enfermedad pulmonar obstructiva cr\u00f3nica e infecci\u00f3n por SARS-CoV-2. \u00bfQu\u00e9 sabemos hasta ahora?/ Chronic Obstructive Pulmonary Disease and SARS-CoV-2 Infection. What Do We Know so Far? Content:", "qid": 32, "docid": "jz1z7fcx", "rank": 53, "score": 8.681099891662598}, {"content": "Title: Extrapulmonary Manifestations of SARS-CoV-2: A Brief Review Content: On December 30, 2019, the first reports of a group of patients with unknown etiology pneumonia appeared in Wuhan city, Hubei province, China Taking into consideration the large amount of similar nucleotide sequences between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the past epidemic coronavirus, it will be appropriate to expect that such pathogens share the same cell line tropism and systemic pathology Although several studies have, so far, identified the clinical characteristics of COVID-19 cases, there is very little knowledge on the extrapulmonary affection of SARS-CoV-2 In this review, we summarize reports of the main affected organs besides the pulmonary system such as the liver and kidneys, as well as the cardiovascular and nervous system The mechanisms of lesion remain largely unclear The approach of this investigation is to suggest multisystemic work-up in patients with SARS-CoV-2 infection, aside from its respiratory management Correspondence to: Mar\u00eda Fernanda Osorio Pesantes, MD, School of Medicine, Universidad Esp\u00edritu Santo-Ecuador, Av Samborond\u00f3n S/N, Guayaquil 092301, Ecuador E-mail: maferosorio@uees edu ec The authors have no funding or conflicts of interest to disclose Author Statement: M F O and R G V participated in writing the original draft, and review and editing This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections Copyright \u00a9 2020 Wolters Kluwer Health, Inc All rights reserved", "qid": 32, "docid": "q5kdm55n", "rank": 54, "score": 8.661199569702148}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: Background: This study\u2019s aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \u201cWhat are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\u201d Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 32, "docid": "irocv0ke", "rank": 55, "score": 8.659799575805664}, {"content": "Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: BACKGROUND: This study's aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. METHODS: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, \"What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?\" RESULTS: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. CONCLUSIONS: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.", "qid": 32, "docid": "o7ze1myf", "rank": 56, "score": 8.659798622131348}, {"content": "Title: Discharged COVID-19 Patients Testing Positive Again for SARS-CoV-2 RNA: A Minireview of Published Studies from China Content: In the ongoing COVID-19 pandemic, one potential cause of concern is that some discharged COVID-19 patients are testing positive again for SARS-CoV-2 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS-CoV-2 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT-PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID-19 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "59prqbb3", "rank": 57, "score": 8.645400047302246}, {"content": "Title: Discharged COVID\u201019 Patients Testing Positive Again for SARS\u2010CoV\u20102 RNA: A Minireview of Published Studies from China Content: In the ongoing COVID\u201019 pandemic, one potential cause of concern is that some discharged COVID\u201019 patients are testing positive again for SARS\u2010CoV\u20102 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS\u2010CoV\u20102 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT\u2010PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID\u201019 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "snajbvr9", "rank": 58, "score": 8.64539909362793}, {"content": "Title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) Content: Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.", "qid": 32, "docid": "3y47oszt", "rank": 59, "score": 8.644800186157227}, {"content": "Title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19). Content: Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.", "qid": 32, "docid": "r2rnnsfh", "rank": 60, "score": 8.64479923248291}, {"content": "Title: Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not? Content: Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic", "qid": 32, "docid": "03vy3uaj", "rank": 61, "score": 8.60990047454834}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not Content: Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.", "qid": 32, "docid": "18q23z8l", "rank": 62, "score": 8.609899520874023}, {"content": "Title: On the sensitivity of non-pharmaceutical intervention models for SARS-CoV-2 spread estimation Content: Introduction: A series of modelling reports that quantify the effect of non pharmaceutical interventions (NPIs) on the spread of the SARS-CoV-2 virus have been made available prior to external scientific peer-review. The aim of this study was to investigate the method used by the Imperial College COVID-19 Research Team (ICCRT) for estimation of NPI effects from the system theoretical viewpoint of model identifiability. Methods: An input-sensitivity analysis was performed by running the original software code of the systems model that was devised to estimate the impact of NPIs on the reproduction number of the SARS-CoV-2 infection and presented online by ICCRT in Report 13 on March 30 2020. An empirical investigation was complemented by an analysis of practical parameter identifiability, using an estimation theoretical framework. Results: Despite being simplistic with few free parameters, the system model was found to suffer from severe input sensitivities. Our analysis indicated that the model lacks practical parameter identifiability from data. The analysis also showed that this limitation is fundamental, and not something readily resolved should the model be driven with data of higher reliability. Discussion: Reports based on system models have been instrumental to policymaking during the SARS-CoV-2 pandemic. With much at stake during all phases of a pandemic, we conclude that it is crucial to thoroughly scrutinise any SARS-CoV-2 effect analysis or prediction model prior to considering its use as decision support in policymaking. The enclosed example illustrates what such a review might reveal.", "qid": 32, "docid": "2zkrbjqe", "rank": 63, "score": 8.580499649047852}, {"content": "Title: Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.", "qid": 32, "docid": "okrpa7k7", "rank": 64, "score": 8.57610034942627}, {"content": "Title: Why does Japan have so few cases of COVID-19? Content: The COVID-19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS-CoV-2 infections.", "qid": 32, "docid": "9ixbawvv", "rank": 65, "score": 8.545599937438965}, {"content": "Title: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Content: Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to nearly 190 countries. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood lab profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.", "qid": 32, "docid": "7rh07bii", "rank": 66, "score": 8.540499687194824}, {"content": "Title: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Content: Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to more than 200 countries or territories. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood laboratory profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.", "qid": 32, "docid": "uojjp4dd", "rank": 67, "score": 8.540498733520508}, {"content": "Title: Biological Warfare: Infectious Disease and Bioterrorism Content: The term biological warfare typically conjures images of medieval warriors tossing dead cattle over city walls or clandestine government agents secretly releasing mysterious microbes into enemy territory. Of course, biological warfare does encompass such activity, but the vast majority of what constitutes biological warfare is far more mundane. Ever since life evolved on earth about 3.8 billion years ago, organisms have constantly devised new ways to kill each other. Any organism that makes use of toxins\u2014from bacteria to snakes\u2014is engaging in a form of biological warfare. Humans who engage in biological warfare do so by taking advantage of these toxin-producing organisms.", "qid": 32, "docid": "dbuy7vvw", "rank": 68, "score": 8.517000198364258}, {"content": "Title: COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Content: A severe outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019, and spread so rapidly that more than 200,000 cases have so far been reported worldwide; on January 30, 2020, the WHO declared it the sixth public health emergency of international concern. The two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) share similar pathogenetic, epidemiological and clinical features as COVID-19. As little is currently known about SARS-CoV-2, it is likely that lessons learned from these major epidemics can be applied to the new pandemic, including the use of novel immunosuppressive drugs.", "qid": 32, "docid": "7hw4nzwp", "rank": 69, "score": 8.511199951171875}, {"content": "Title: Why does the coronavirus spread so easily between people? Content: As the number of coronavirus infections approaches 100,000 people worldwide, researchers are racing to understand what makes it spread so easily A handful of genetic and structural analyses have identified a key feature of the virus \u2014 a protein on its surface \u2014 that might explain why it infects human cells so readily Other groups are investigating the doorway through which the new coronavirus enters human tissues \u2014 a receptor on cell membranes Both the cell receptor and the virus protein offer potential targets for drugs to block the pathogen, but researchers say it is too early to be sure \u201cUnderstanding transmission of the virus is key to its containment and future prevention,\u201d says David Veesler, a structural virologist at the University of Washington in Seattle, who posted his team\u2019s findings about the virus protein on the biomedical preprint server bioRxiv on 20 February1 The new virus spreads much more readily than the one that caused severe acute respiratory syndrome, or SARS (also a coronavirus), and has infected more than ten times the number of people who contracted SARS", "qid": 32, "docid": "u1claajf", "rank": 70, "score": 8.510600090026855}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "qid": 32, "docid": "3mnmib3o", "rank": 71, "score": 8.50730037689209}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research. Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "qid": 32, "docid": "sn72mkzq", "rank": 72, "score": 8.507299423217773}, {"content": "Title: Why does Japan have so few cases of COVID\u201019? Content: The COVID\u201019 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS\u2010CoV\u20102 infections.[Image: see text]", "qid": 32, "docid": "gujyen9k", "rank": 73, "score": 8.489999771118164}, {"content": "Title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results Content: Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of \u201cno virus signal\u201d is insufficient for clinical interpretation: controls must also say \u201cThe reaction worked as intended and would have found virus if present.\u201d Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an \u201cextraction control success\u201d signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of \u201cno virus detected, control succeeded\u201d following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear. One Sentence Summary A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing \u201cNo\u201d with \u201cDon\u2019t know\u201d \u2013 but it\u2019s fixable", "qid": 32, "docid": "n6811ens", "rank": 74, "score": 8.455400466918945}, {"content": "Title: Sars-CoV-2: A clinical update - II Content: INTRODUCTION: A covid-19 pandemic decreed by WHO has raised greater awareness of it EPIDEMIOLOGY: The infection, reached the mark of 2,000,000 patients in 33 countries and caused the risk of the presence of comorbidities and advanced age TRANSMISSIBILITY: The transmissibility calculated so far is similar to the H1N1 epidemic, but with lower mortality rates PHYSIOPATHOLOGY: The SARS-CoV-2 virus, of the Coronaviridae family, has the capacity for cellular invasion through the angiotensin-converting enzyme 2 does not have a lower respiratory epithelium and in the cells of the small intestine mucosa CLINICAL MANIFESTATIONS: a presentation can be divided into mild (fever, fatigue, cough, myalgia, and sputum) and severe (cyanosis, dyspnoea, tachypnea, chest pain, hypoxemia and need for clinical measurement) and has an estimated estimate of 2% DIAGNOSIS: allows the detection of viral load in CRP-TR of patients with high clinical suspicion TREATMENT: based on supportive measures and infection control In severe cases, the use of medications such as hydroxychloroquine and azithromycin or medication can be promising Take care to avoid the use of corticosteroids There are no restrictions on the use of resources and IECAs / BRAs", "qid": 32, "docid": "idta8vnq", "rank": 75, "score": 8.416999816894531}, {"content": "Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "qid": 32, "docid": "5zb96j4a", "rank": 76, "score": 8.416600227355957}, {"content": "Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features , Copyright Notice (C) 2020 Royal College of Physicians", "qid": 32, "docid": "9griuata", "rank": 77, "score": 8.41450023651123}, {"content": "Title: Dermatologists and SARS\u2010CoV\u20102: The impact of the pandemic on daily practice Content: Since the first case of \u201cpneumonia of unknown aetiology\u201d was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as \u201csevere acute respiratory syndrome coronavirus 2\u201d (SARS\u2010CoV\u20102) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease\u201019 (COVID\u2010 19) and satisfying the epidemiological criteria for a label of \u201cpandemic.\u201d The ongoing SARS\u2010CoV\u20102 pandemic is having a huge impact on dermatological practice including the marked reduction of face\u2010to\u2010face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID\u201019 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID\u201019 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS\u2010CoV\u20102 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS\u2010CoV\u20102 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS\u2010CoV\u20102 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID\u201019 disaster. Learning from experience may help to cope with future major societal changes.", "qid": 32, "docid": "erntrh3p", "rank": 78, "score": 8.404500007629395}, {"content": "Title: Dermatologists and SARS-CoV-2: the impact of the pandemic on daily practice Content: Since the first case of 'pneumonia of unknown aetiology' was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognized thereafter as 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) has spread over the four continents, causing the respiratory manifestations of coronavirus disease-19 (COVID-19) and satisfying the epidemiological criteria for a label of 'pandemic'. The ongoing SARS-CoV-2 pandemic is having a huge impact on dermatological practice including the marked reduction of face-to-face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID-19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID-19 care for patient assistance and new research needs to be addressed. It is not known yet if skin lesions and derangement of the skin barrier could make it easier for SARS-CoV-2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS-CoV-2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS-CoV-2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID-19 disaster. Learning from experience may help to cope with future major societal changes.", "qid": 32, "docid": "hl1eq3eb", "rank": 79, "score": 8.404499053955078}, {"content": "Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.", "qid": 32, "docid": "svo94kuo", "rank": 80, "score": 8.388400077819824}, {"content": "Title: On the evolutionary epidemiology of SARS-CoV-2 Content: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.", "qid": 32, "docid": "ig0rnbqb", "rank": 81, "score": 8.362799644470215}, {"content": "Title: Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes Content: COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.", "qid": 32, "docid": "bbhf4qus", "rank": 82, "score": 8.356499671936035}, {"content": "Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded &#945;-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.", "qid": 32, "docid": "gykudnxf", "rank": 83, "score": 8.349200248718262}, {"content": "Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded \u03b1-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M(pro) (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 M(pro) for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 M(pro) active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M(pro) protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.", "qid": 32, "docid": "hgpfib1z", "rank": 84, "score": 8.349199295043945}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. Content: UNLABELLED Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCE The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.", "qid": 32, "docid": "nttnaal7", "rank": 85, "score": 8.347800254821777}, {"content": "Title: Fight against novel coronavirus: A perspective of medicinal chemists Content: The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.", "qid": 32, "docid": "50db66ru", "rank": 86, "score": 8.333200454711914}, {"content": "Title: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA Content: SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.", "qid": 32, "docid": "twm32weg", "rank": 87, "score": 8.307999610900879}, {"content": "Title: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA. Content: SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.", "qid": 32, "docid": "xmg9tnda", "rank": 88, "score": 8.307998657226562}, {"content": "Title: Potential for elimination of SAR-CoV-2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, future vaccination against COVID-19 may fall into long-term costly guerrilla warfare between SARS-CoV-2 and humans. Elimination of SARS-CoV-2 through vaccination to avoid the potential long-term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to the elimination of three human influenza viruses, which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggest that the rapid establishment of global herd immunity through mass vaccination using an appropriate vaccine could eliminate SARS-CoV-2. The coming 2 years are a golden time for elimination through vaccination, which requires tremendous national and international collaboration. This review also prioritizes the efficacy of vaccines for COVID-19 and elucidates the importance of the development of more live vaccines for COVID-19.", "qid": 32, "docid": "vl3j05bs", "rank": 89, "score": 8.270500183105469}, {"content": "Title: Novel coronavirus SARS-CoV-2 and COVID-19. Practice recommendations for obstetric anaesthesia: what we have learned thus far Content: \u2022 Pregnancy does not seem to be associated with more severe COVID-19 infections. \u2022 Risk of antenatal vertical transmission of COVID-19 is low. \u2022 Epidural analgesia should be considered, provided platelet counts are not low. \u2022 Droplet precautions are indicated for all women with suspected COVID-19. \u2022 Airborne precautions recommended for general anaesthesia or higher risk thereof.", "qid": 32, "docid": "dhrtpo56", "rank": 90, "score": 8.24530029296875}, {"content": "Title: SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review Content: SARS-CoV-2, the virus that causes COVID-19, has been found in the faeces of infected patients in numerous studies. Stool may remain positive for SARS-CoV-2, even when the respiratory tract becomes negative, and the interaction with the gastrointestinal tract poses a series of questions about wastewater and its treatments. This review aims to understand the viral load of SARS-CoV-2 in faeces and sewage and its fate in wastewater treatment plants (WWTPs). The viral load in the faeces of persons testing positive for SARS-CoV-2 was estimated at between 5\u00b7103 to 107.6 copies/mL, depending on the infection course. In the sewerage, faeces undergo dilution and viral load decreases considerably in the wastewater entering a WWTP with a range from 2 copies/100 mL to 3\u00b7103 copies/mL, depending on the level of the epidemic. Monitoring of SARS-CoV-2 in sewage, although no evidence of COVID-19 transmission has been found via this route, could be advantageously exploited as an early warning of outbreaks. Preliminary studies on WBE seem promising; but high uncertainty of viral loads in wastewater and faeces remains, and further research is needed. The detection of SARS-CoV-2 in sewage, based on RNA sequences and RT-PCR, requires a shared approach on sample pre-treatment and on-site collection to ensure comparable results. The finding of viral RNA in stools does not imply that the virus is viable and infectious. Viability of CoVs such as SARS-CoV-2 decreases in wastewater - due to temperature, pH, solids, micropollutants - but high inactivation in WWTPs can be obtained only by using disinfection (free chlorine, UVC light). A reduction in the quantity of disinfectants can be obtained by implementing Membrane-Bioreactors with ultrafiltration to separate SARS-CoV-2 virions with a size of 60-140 nm. In sludge treatment, thermophilic digestion is effective, based on the general consensus that CoVs are highly sensitive to increased temperatures.", "qid": 32, "docid": "8plkh5g8", "rank": 91, "score": 8.208499908447266}, {"content": "Title: SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review Content: Abstract SARS-CoV-2, the virus that causes COVID-19, has been found in the faeces of infected patients in numerous studies. Stool may remain positive for SARS-CoV-2, even when the respiratory tract becomes negative, and the interaction with the gastrointestinal tract poses a series of questions about wastewater and its treatments. This review aims to understand the viral load of SARS-CoV-2 in faeces and sewage and its fate in wastewater treatment plants (WWTPs). The viral load in the faeces of persons testing positive for SARS-CoV-2 was estimated at between 5\u00b7103 to 107.6 copies/mL, depending on the infection course. In the sewerage, faeces undergo dilution and viral load decreases considerably in the wastewater entering a WWTP with a range from 2 copies/100 mL to 3\u00b7103 copies/mL, depending on the level of the epidemic. Monitoring of SARS-CoV-2 in sewage, although no evidence of COVID-19 transmission has been found via this route, could be advantageously exploited as an early warning of outbreaks. Preliminary studies on WBE seem promising; but high uncertainty of viral loads in wastewater and faeces remains, and further research is needed. The detection of SARS-CoV-2 in sewage, based on RNA sequences and RT-PCR, requires a shared approach on sample pre-treatment and on-site collection to ensure comparable results. The finding of viral RNA in stools does not imply that the virus is viable and infectious. Viability of CoVs such as SARS-CoV-2 decreases in wastewater - due to temperature, pH, solids, micropollutants - but high inactivation in WWTPs can be obtained only by using disinfection (free chlorine, UVC light). A reduction in the quantity of disinfectants can be obtained by implementing Membrane-Bioreactors with ultrafiltration to separate SARS-CoV-2 virions with a size of 60\u2013140 nm. In sludge treatment, thermophilic digestion is effective, based on the general consensus that CoVs are highly sensitive to increased temperatures.", "qid": 32, "docid": "wcn6o3fd", "rank": 92, "score": 8.20849895477295}, {"content": "Title: Potential for elimination of SAR\u2010CoV\u20102 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination Content: The ongoing pandemic of coronavirus disease 2019 (COVID\u201019) caused by the novel virus SARS\u2010CoV\u20102 has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, the future vaccination against COVID\u201019 may fall into long\u2010term costly guerrilla warfare between SARS\u2010CoV\u20102 and humans. Elimination of SARS\u2010CoV\u20102 through vaccination to avoid the potential long\u2010term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to elimination of three human influenza viruses which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggested that rapid establishment of global herd immunity through mass vaccination using a proper vaccine could eliminate SARS\u2010CoV\u20102. The coming two years is the golden time for the elimination through vaccination which requires tremendous national and international collaboration. This review also prioritized the efficacy of vaccines for COVID\u201019 and elucidated the importance for development of more live vaccines for COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "afpbaqgx", "rank": 93, "score": 8.2076997756958}, {"content": "Title: Epidemiological and clinical features of asymptomatic patients with SARS\u2010CoV\u20102 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS\u2010CoV\u20102 without any symptoms. Patients with confirmed SARS\u2010CoV\u20102 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS\u2010CoV\u20102 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS\u2010CoV\u20102 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0\u201015.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS\u2010CoV\u20102 in throat swabs, while one patient was only tested positive for SARS\u2010CoV\u20102 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS\u2010CoV\u20102 tested negative from admission was 7.0 days (IQR: 4.0\u20109.0 days). Patients without any symptoms but with SARS\u2010CoV\u20102 exposure should be closely monitored and tested for SARS\u2010CoV\u20102 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS\u2010CoV\u20102 have favorable outcomes.", "qid": 32, "docid": "4ki5st9h", "rank": 94, "score": 8.186599731445312}, {"content": "Title: Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.", "qid": 32, "docid": "dud6dzp6", "rank": 95, "score": 8.186598777770996}, {"content": "Title: Neurological Insights of COVID-19 Pandemic Content: The novel coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The virus is unlike its previous counterparts, SARS-CoV and MERS-CoV, or anything the world has encountered before both in terms of virulence and severity of the infection. If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. Recent reports suggest that it is not just the lung that the virus may be targeting; the human brain may soon emerge as the new abode of the virus. Already instances of patients with COVID-19 have been reported with mild (anosmia and ageusia) to severe (encephalopathy) neurological manifestations, and if that is so, then it gives us more reasons to be frightened of this killer virus. Keeping in mind that the situation does not worsen from here, immediate awareness and more thorough research regarding the neuroinvasive nature of the virus is the immediate need of the hour. Scientists globally also need to up their game to design more specific therapeutic strategies with the available information to counteract the pandemic. In this Viewpoint, we provide a brief outline of the currently known neurological manifestations of COVID-19 and discuss some probable ways to design therapeutic strategies to overcome the present global crisis.", "qid": 32, "docid": "b6qts3n0", "rank": 96, "score": 8.16819953918457}, {"content": "Title: Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis. Content: Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.", "qid": 32, "docid": "di8lljoi", "rank": 97, "score": 8.167400360107422}, {"content": "Title: COVID-19 and the Cerebro-Cardiovascular Systems: What do we Know so Far? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of 2019-2020 has resulted in multiple hospitalizations, deaths and economic hardships worldwide. Though respiratory involvement in patients with coronavirus disease 2019 (COVID-19) is well-known, the potential cardiovascular and cerebrovascular manifestations are less-understood. We performed a PubMed and Google Scholar search and reviewed relevant literature regarding COVID-19 and cardiovascular system involvement. SARS-CoV-2 possesses high-affinity for angiotensin converting enzyme 2 (ACE2) receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID-19 cases. Pre-existing cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk-factor for severe infection. Based on our review of published studies, COVID-19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects and acute stroke and are likely to have poorer outcomes as a result. As the COVID-19 pandemic continues, more data regarding potential cardiovascular and cerebrovascular manifestations of the disease is required.", "qid": 32, "docid": "sam3usz7", "rank": 98, "score": 8.16510009765625}, {"content": "Title: SARS\u2010CoV\u20102: What do we know so far? Content: We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and patients with underlying comorbidities are at a higher risk of death. We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia.", "qid": 32, "docid": "9pdakwmb", "rank": 99, "score": 8.153599739074707}, {"content": "Title: Acute Coronary Syndromes and Covid-19: Exploring the Uncertainties. Content: Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. The initial data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss the pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; and learnings that have emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.", "qid": 32, "docid": "dtc5w5xs", "rank": 100, "score": 8.151200294494629}]}
{"query": "What vaccine candidates are being tested for Covid-19?", "hits": [{"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 33, "docid": "khfiy0m2", "rank": 1, "score": 10.20740032196045}, {"content": "Title: SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds. Content: In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "qid": 33, "docid": "y883anmp", "rank": 2, "score": 10.207399368286133}, {"content": "Title: Drug Repurposing to find Inhibitors of SARS-CoV-2 Main Protease Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. Currently there is no known vaccine or specific antiviral treatment for COVID-19 and so, there is an urgent need for expedite discovery of new therapeutics to combat the disease until a vaccine will be available worldwide. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage (over conventional approaches that attempt to develop a drug from scratch) that time frame of the overall process can be significantly reduced because of the few number of clinical trial required. In this work, a virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. As a result of this study, 12 drugs are proposed as candidates for inhibitors of the Mpro enzyme. Some of the selected compounds are antiviral drugs that are already being tested in COVID-19 clinical trials (i.e. ribavirin) or are used to alleviate symptoms of the disease (i.e. codeine). Surprisingly, the most promising candidate is the naturally occurring broad spectrum antibiotic oxytetracycline. This compound has largely outperformed the remaining selected candidates along all filtering steps of our virtual screening protocol. If the activity of any of these drugs is experimentally corroborated, they could be used directly in clinical trials without the need for pre-clinical testing or safety evaluation since they are already used as drugs for other diseases.", "qid": 33, "docid": "z17knvts", "rank": 3, "score": 9.247200012207031}, {"content": "Title: Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19 Content: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness and death. Currently, there are no specific antiviral drugs that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein and the highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.", "qid": 33, "docid": "79yna07e", "rank": 4, "score": 9.221500396728516}, {"content": "Title: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials Content: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "qid": 33, "docid": "p36zubnf", "rank": 5, "score": 9.055700302124023}, {"content": "Title: The potential danger of suboptimal antibody responses in COVID-19 Content: There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.", "qid": 33, "docid": "xee6npr3", "rank": 6, "score": 8.882599830627441}, {"content": "Title: From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons? Content: It is often said that it takes 17 years to move medical research from bench to bedside. In a coronavirus disease (COVID-19) world, such time-lags feel intolerable. In these extraordinary circumstances could years be made into months? If so, could those lessons be used to accelerate medical research when the crisis eases?To measure time-lags in health and biomedical research as well as to identify ways of reducing them, we developed and published (in 2015) a matrix consisting of overlapping tracks (or stages/phases) in the translation from discovery research to developed products, policies and practice. The matrix aids analysis by highlighting the time and actions required to develop research (and its translation) both (1) along each track and (2) from one track to another, e.g. from the discovery track to the research-in-humans track. We noted four main approaches to reducing time-lags, namely increasing resources, working in parallel, starting or working at risk, and improving processes.Examining these approaches alongside the matrix helps interpret the enormous global effort to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of COVID-19. Rapid progress in the discovery/basic and human research tracks is being made through a combination of large-scale funding, work being conducted in parallel (between different teams globally and through working in overlapping tracks), working at greater (but proportionate) risk to safety than usual, and adopting various new processes. The overlapping work of some of the teams involves continuing animal research whilst entering vaccine candidates into Phase I trials alongside planning their Phase II trials. The additional funding available helps to reduce some of the usual financial risks in moving so quickly. Going forward through the increasingly large human trials for safety, dosage and efficacy, it will be vital to overlap work in parallel in the often challenging public policy and clinical tracks. Thus, regulatory and reimbursement bodies are beginning and preparing rapid action to pull vaccines proving to be safe and effective through to extraordinarily rapid application to the general population. Monitoring the development of a COVID-19 vaccine using the matrix (modified as necessary) could help identify which of the approaches speeding development and deployment could be usefully applied more widely in the future.", "qid": 33, "docid": "t9r46ci4", "rank": 7, "score": 8.806900024414062}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus. Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 33, "docid": "sdtiyrab", "rank": 8, "score": 8.782899856567383}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 33, "docid": "z5q82rmp", "rank": 9, "score": 8.782898902893066}, {"content": "Title: From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons? Content: It is often said that it takes 17 years to move medical research from bench to bedside. In a coronavirus disease (COVID-19) world, such time-lags feel intolerable. In these extraordinary circumstances could years be made into months? If so, could those lessons be used to accelerate medical research when the crisis eases? To measure time-lags in health and biomedical research as well as to identify ways of reducing them, we developed and published (in 2015) a matrix consisting of overlapping tracks (or stages/phases) in the translation from discovery research to developed products, policies and practice. The matrix aids analysis by highlighting the time and actions required to develop research (and its translation) both (1) along each track and (2) from one track to another, e.g. from the discovery track to the research-in-humans track. We noted four main approaches to reducing time-lags, namely increasing resources, working in parallel, starting or working at risk, and improving processes. Examining these approaches alongside the matrix helps interpret the enormous global effort to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of COVID-19. Rapid progress in the discovery/basic and human research tracks is being made through a combination of large-scale funding, work being conducted in parallel (between different teams globally and through working in overlapping tracks), working at greater (but proportionate) risk to safety than usual, and adopting various new processes. The overlapping work of some of the teams involves continuing animal research whilst entering vaccine candidates into Phase I trials alongside planning their Phase II trials. The additional funding available helps to reduce some of the usual financial risks in moving so quickly. Going forward through the increasingly large human trials for safety, dosage and efficacy, it will be vital to overlap work in parallel in the often challenging public policy and clinical tracks. Thus, regulatory and reimbursement bodies are beginning and preparing rapid action to pull vaccines proving to be safe and effective through to extraordinarily rapid application to the general population. Monitoring the development of a COVID-19 vaccine using the matrix (modified as necessary) could help identify which of the approaches speeding development and deployment could be usefully applied more widely in the future.", "qid": 33, "docid": "xtxfadn9", "rank": 10, "score": 8.686300277709961}, {"content": "Title: Another Set of Coronavirus Vaccine Candidates Content: I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting) Now it\u2019s time to look at several programs that aren\u2019t in either of those, but still have plenty of serious science behind them For an example of a relatively new technology that\u2019s now in use for human patients, there\u2019s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck Stat has an excellent long-form article from earlier this year about how this came about, and it\u2019s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they\u2019re using those lessons in their current work If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors \u2013 this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses I don\u2019t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2 These projects are aiming at FDA approval for Phase I trials, but there\u2019s no word yet on what such an application might go in", "qid": 33, "docid": "zwf26o63", "rank": 11, "score": 8.52079963684082}, {"content": "Title: Consensus Summary Report for CEPI/BC March 12-13, 2020 Meeting: Assessment of Risk of Disease Enhancement with COVID-19 Vaccines Content: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of \u201cdisease enhancement\u201d has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory Syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.", "qid": 33, "docid": "eeh2a0t8", "rank": 12, "score": 8.517000198364258}, {"content": "Title: Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines Content: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of \"disease enhancement\" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.", "qid": 33, "docid": "g4ak4t31", "rank": 13, "score": 8.516999244689941}, {"content": "Title: Products in a Pandemic: Liability for Medical Products and the Fight against COVID-19 Content: A multitude of medical products are being developed and produced as part of efforts to tackle COVID-19. They are varied in nature and range from test kits to tracing apps, protective equipment, ventilators, medicines and, of course, vaccines. The design, testing and manufacture of many of these products differs from production in normal times due to the urgency of the situation and the rapid increase in demand created by the pandemic. This article considers the legal issues arising as a result of the production of emergency products, particularly from a products liability perspective. To what extent do existing concepts under the European Product Liability Directive, such as defect, causation and the various defences, permit the pandemic to be taken into account when a Court is considering issues of liability? What is the impact on liability of the modified regulatory regime? In light of that discussion, the case for alternative responses is examined from a comparative and European perspective, including the issue of Government indemnities for the manufacturers of products, legal exemptions from liability and alternative no-fault compensation schemes.", "qid": 33, "docid": "sjub0mwv", "rank": 14, "score": 8.444100379943848}, {"content": "Title: Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus Content: PURPOSE OF REVIEW: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is listed in the World Health Organization\u2019s blueprint of priority diseases that need immediate research. Camels are reservoirs of this virus, and the virus spills over into humans through direct contact with camels. Human-to-human transmission and travel-associated cases have been identified as well. Limited studies have characterized the molecular pathogenesis of MERS-CoV. Most studies have used ectopic expression of viral proteins to characterize MERS-CoV and its ability to modulate antiviral responses in human cells. Studies with live virus are limited, largely due to the requirement of high containment laboratories. In this review, we have summarized current studies on MERS-CoV molecular pathogenesis and have mentioned some recent strategies that are being developed to control MERS-CoV infection. RECENT FINDINGS: Multiple antiviral molecules with the potential to inhibit MERS-CoV infection by disrupting virus-receptor interactions are being developed and tested. Although human vaccine candidates are still being developed, a candidate camel vaccine is being tested for efficacy. Combination of supportive treatment with interferon and antivirals is also being explored. SUMMARY: New antiviral molecules that inhibit MERS-CoV and host cell receptor interaction may become available in the future. Additional studies are required to identify and characterize the pathogenesis of MERS-CoV EMC/2012 and other circulating strains. An effective MERS-CoV vaccine, for humans and/or camels, along with an efficient combination antiviral therapy may help us prevent future MERS cases.", "qid": 33, "docid": "bftsmcl4", "rank": 15, "score": 8.328700065612793}, {"content": "Title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Content: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.", "qid": 33, "docid": "iymmf4k6", "rank": 16, "score": 8.246999740600586}, {"content": "Title: Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines Content: The COVID-19 pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 33, "docid": "0g7a9s5z", "rank": 17, "score": 8.232500076293945}, {"content": "Title: Fighting COVID-19: A quick review of diagnoses, therapies, and vaccines Content: The coronavirus disease 2019 (COVID-19) pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 33, "docid": "2vevp0fg", "rank": 18, "score": 8.232499122619629}, {"content": "Title: A review on possible modes of actions of Chloroquine/ Hydroxychloroquine: Repurposing against SAR-COV-2 (COVID 19) pandemic Content: The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have been used as frontline drugs for treatment and prophylaxis against all types of human malaria worldwide. Since late December 2019, humans have been under threat due to an outbreak of a novel coronavirus (SARS-CoV-2) disease (COVID-19; previously known as 2019-nCoV), since its first reported cases in Wuhan, China [1]. Consequently, the virus infection has been declared a pandemic. While the World is finding expedited approvals for the development of vaccine, which is time dependent, being preventative and not possibly a cure, physicians and countries\u2019 leaders are considering several concerted clinical trials suggesting that this age-old antimalarial drug, CQ/HCQ could be a potent therapeutic agent against COVID-19 infection. Based on accumulating scientific reports, we have highlighted in this review, the different possible modes of action of chloroquine/hydroxychloroquine that could particularly justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of using the drugs and repurposing of old drugs in this instance, chloroquine and hydroxychloroquine, specifically, hydroxychloroquine in the treatment of SARS-CoV-2 could be the best choice. CQ/HCQ has diverse modes of action, like alteration of acidic environment inside lysosome, late endosomes, restriction further with endocytosis, exsosome release, phagolysosomal fusion in systematically and subsequently inhibition of cytokine storm in host cell. One or sum of diverse mechanisms might work against the viral infections and help prevent more deaths. Given that there is no cure for COVID-19, the clinical testing of HCQ is urgently needed to ascertain its potency against the virus as this is the current available treatment option. There is still a need to find other innovative drug candidates as other possible candidate to go into clinical evaluation and testing.", "qid": 33, "docid": "lb2ybn0b", "rank": 19, "score": 8.120400428771973}, {"content": "Title: A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.", "qid": 33, "docid": "ptvsie6m", "rank": 20, "score": 8.10200023651123}, {"content": "Title: What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19? Content: The emergence of new pathogenic viral strains is a constant threat to global health, with the new coronavirus strain COVID-19 as the latest example. COVID-19, caused by the SARS-CoV-2 virus has quickly spread around the globe. This pandemic demands rapid development of drugs and vaccines. Plant-based vaccines are a technology with proven viability, which have led to promising results for candidates evaluated at the clinical level, meaning this technology could contribute towards the fight against COVID-19. Herein, a perspective in how plant-based vaccines can be developed against COVID-19 is presented. Injectable vaccines could be generated by using transient expression systems, which offer the highest protein yields and are already adopted at the industrial level to produce VLPs-vaccines and other biopharmaceuticals under GMPC-processes. Stably-transformed plants are another option, but this approach requires more time for the development of antigen-producing lines. Nonetheless, this approach offers the possibility of developing oral vaccines in which the plant cell could act as the antigen delivery agent. Therefore, this is the most attractive approach in terms of cost, easy delivery, and mucosal immunity induction. The development of multiepitope, rationally-designed vaccines is also discussed regarding the experience gained in expression of chimeric immunogenic proteins in plant systems.", "qid": 33, "docid": "df36w6l7", "rank": 21, "score": 8.05150032043457}, {"content": "Title: Current Therapies Under Investigation for COVID-19 Content: In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This mini-review also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV.", "qid": 33, "docid": "050fdtm8", "rank": 22, "score": 7.94920015335083}, {"content": "Title: Current Therapies Under Investigation for COVID-19. Content: In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This mini-review also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV.", "qid": 33, "docid": "u3xxshqw", "rank": 23, "score": 7.949199199676514}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.", "qid": 33, "docid": "7h3rrea7", "rank": 24, "score": 7.928999900817871}, {"content": "Title: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study Content: COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.", "qid": 33, "docid": "fbm3zoe2", "rank": 25, "score": 7.85830020904541}, {"content": "Title: The potential of cannabidiol in the COVID-19 pandemic: a hypothesis letter Content: Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High-CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPAR\u00ce\u00b3 agonist, it can display a direct antiviral activity 4) PPAR\u00ce\u00b3 agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID-19 pandemic.", "qid": 33, "docid": "7d5hq0mq", "rank": 26, "score": 7.814000129699707}, {"content": "Title: The potential of cannabidiol in the COVID\u201019 pandemic: a hypothesis letter Content: Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid\u201019) is crucial, pending a vaccine against SARS\u2010CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non\u2010psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High\u2010CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS\u2010CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti\u2010inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPAR\u03b3 agonist, it can display a direct antiviral activity 4) PPAR\u03b3 agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID\u201019 pandemic.", "qid": 33, "docid": "orw69y3q", "rank": 27, "score": 7.813999176025391}, {"content": "Title: Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines Content: Summary Background In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. 1,2 The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. Methods We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. Findings A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. Interpretation The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.", "qid": 33, "docid": "6t0wpiqy", "rank": 28, "score": 7.795000076293945}, {"content": "Title: Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients Content: In the absence of approved drugs or vaccines, there is a pressing need to develop tools for therapy and prevention of Covid-19. Human monoclonal antibodies have very good probability of being safe and effective tools for therapy and prevention of SARS-CoV-2 infection and disease. Here we describe the screening of PBMCs from seven people who survived Covid-19 infection to isolate human monoclonal antibodies against SARS-CoV-2. Over 1,100 memory B cells were single-cell sorted using the stabilized prefusion form of the spike protein and incubated for two weeks to allow natural production of antibodies. Supernatants from each cell were tested by ELISA for spike protein binding, and positive antibodies were further tested for neutralization of spike binding to receptor(s) on Vero E6 cells and for virus neutralization in vitro. From the 1,167 memory B specific for SARS-CoV-2, we recovered 318 B lymphocytes expressing human monoclonals recognizing the spike protein and 74 of these were able to inhibit the binding of the spike protein to the receptor. Finally, 17 mAbs were able to neutralize the virus when assessed for neutralization in vitro. Lead candidates to progress into the drug development pipeline will be selected from the panel of neutralizing antibodies identified with the procedure described in this study. One Sentence Summary Neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for therapeutic and prophylactic interventions.", "qid": 33, "docid": "64y43o0y", "rank": 29, "score": 7.776199817657471}, {"content": "Title: The Importance of Animal Models in the Development of Vaccines Content: Efficient translation of basic vaccine research into clinical therapies greatly depends upon the availability of appropriate animal models. Testing novel vaccine candidates in animal models is a critical step in the development of modern vaccines. Animal models are being used to assess the quality and quantity of the immune response, to identify the optimal route of delivery and formulation, to determine protection from infection and disease transmission, and to evaluate the safety and toxicity of the vaccine formulation. Animal models help to make the translation from basic research to clinical application, and they often allow prediction of the vaccine potential, which helps in predicting the financial risks for vaccine manufacturers. Choosing an appropriate animal model has become increasingly important for the field, as each model has its own advantages and disadvantages. In this review, the criteria for selecting the right animal model, the advantages and disadvantages of various animal models, as well as the future needs for animal models are being discussed.", "qid": 33, "docid": "seaa46hz", "rank": 30, "score": 7.76639986038208}, {"content": "Title: Recombinant Live Vaccines to Protect Against the Severe Acute Respiratory Syndrome Coronavirus Content: The severe acute respiratory syndrome (SARS) coronavirus (CoV) was identified as the etiological agent of an acute respiratory disease causing atypical pneumonia and diarrhea with high mortality. Different types of SARS-CoV vaccines, including nonreplicative and vectored vaccines, have been developed. Administration of these vaccines to animal model systems has shown promise for the generation of efficacious and safe vaccines. Nevertheless, the identification of side effects, preferentially in the elderly animal models, indicates the need to develop novel vaccines that should be tested in improved animal model systems. Live attenuated viruses have generally proven to be the most effective vaccines against viral infections. A limited number of SARS-CoV attenuating modifications have been described, including mutations, and partial or complete gene deletions affecting the replicase, like the nonstructural proteins (nsp1 or nsp2), or the structural genes, and drastic changes in the sequences that regulate the expression of viral subgenomic mRNAs. A promising vaccine candidate developed in our laboratory was based on deletion of the envelope E gene alone, or in combination with the removal of six additional genes nonessential for virus replication. Viruses lacking E protein were attenuated, grew in the lung, and provided homologous and heterologous protection. Improvements of this vaccine candidate have been directed toward increasing virus titers using the power of viruses with mutator phenotypes, while maintaining the attenuated phenotype. The safety of the live SARS-CoV vaccines is being increased by the insertion of complementary modifications in genes nsp1, nsp2, and 3a, by gene scrambling to prevent the rescue of a virulent phenotype by recombination or remodeling of vaccine genomes based on codon deoptimization using synthetic biology. The newly generated vaccine candidates are very promising, but need to be evaluated in animal model systems that include young and aged animals.", "qid": 33, "docid": "1ksz6nmx", "rank": 31, "score": 7.740799903869629}, {"content": "Title: Mental Health Care Providers Dealing With Coronavirus Disease 2019 (COVID-19): What Is the Definition of a Case, How Is That Changing, and What Kinds of Tests Are Available? Content: The goal of this column is to inform mental health care professionals about the evolving way the diagnosis of Coronavirus Disease 2019 (COVID-19) is being made, with emphasis on tests to assist in making the diagnosis and to determine the presence of antibodies to the virus. This column also provides some general information about the disease, its relative risks, and efforts to develop effective treatments. Links to credible websites that are being continuously updated are also provided for readers who want more information and to stay current with ongoing developments.", "qid": 33, "docid": "b5efo2fm", "rank": 32, "score": 7.734000205993652}, {"content": "Title: Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic? Content: Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.", "qid": 33, "docid": "cvwf63zc", "rank": 33, "score": 7.696599960327148}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 33, "docid": "3sepefqa", "rank": 34, "score": 7.618299961090088}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials. Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 33, "docid": "oa8vzf02", "rank": 35, "score": 7.6182990074157715}, {"content": "Title: SARS-CoV-2 in urine. - Should Endourologists be concerned and what PPE measures should be taken to protect the Endourologist when in theatre ? Content: SARS-CoV-2 is usually transmitted through air however several recent reports have found the virus in urine. Only 187 urine samples have been reported to have been tested in the literature to date despite over 4 million cases of respiratory Covid 19 positive cases being reported worldwide. Of these 187 urine tests 6 were positive for the virus and this persisted in urine in once case for up to 42 days. The urine sample was still positive for Covid 19 despite respiratory swabs being negative. There is a potential concern therefore that Endourologists who generally perform a high number of urine prone procedures could be at risk of exposure to the virus peri operatively. There is still confusion as to the type of PPE Endourologists should use and in what circumstances. Until it is proven that urine is not a potential source for transmission of the Virus Endourologists should have a clear knowledge of the different types of PPE available and what they should use when performing procedures.", "qid": 33, "docid": "mk3ley2o", "rank": 36, "score": 7.616300106048584}, {"content": "Title: Covid-19 treatment: The race against time Content: The new outbreak of the novel coronavirus infection emerged in Wuhan-China in late 2019, by the end of Mar 2020, it has spread in more than 178 countries and territories. There is no vaccine or antiviral treatment for COVID-19. Currently, there are several drugs and vaccines being tested for their potential activity against the disease. In this review, we briefly discuss some of the investigational drugs and vaccines being tested against COVID-19 as well as their potential drawbacks.", "qid": 33, "docid": "natp8lbj", "rank": 37, "score": 7.607699871063232}, {"content": "Title: Diagnostic technology for COVID-19: comparative evaluation of antigen and serology-based SARS-CoV-2 immunoassays, and contact tracing solutions for potential use as at-home products Content: As the United States prepares to return to work and open up the economy in the midst of the COVID-19 pandemic without an available vaccine or effective therapy, testing and contact tracing are essential to contain and limit the spread of the COVID-19 virus. In response to the urgent public health need for accurate, effective, low-cost, and scalable COVID-19 testing technology, we evaluated and identified diagnostic solutions with potential for use as an at-home product. We conducted a deep horizon scan for antigen and serology-based diagnostics and down-selected to the most promising technologies. A total of 303 candidate products (138 antibody and 44 antigen tests) were identified. Product evaluations were based entirely on company-provided data. 73 serology-based antibody tests passing an initial scoring algorithm based on specificity and sensitivity data were then further evaluated using a second scoring algorithm. This second algorithm included a review of additional technical specifications of the devices, an analysis of supply chain, manufacturing, and distribution capacity of each vendor. 24 potential antibody products met the selection criteria for further direct laboratory evaluation. The performance metrics for selection of these 24 products are currently being evaluated in a Mass General Brigham laboratory. Testing alone might not be sufficient to prevent the spread of a highly contagious disease like COVID-19. Manual contact tracing could complement testing, but it is likely to fail in identifying many individuals who were in contact with a given COVID patient. The proliferation of smartphones in the population has enabled the development of solutions that can provide public health officials with valuable information for rapid and accurate contact tracing. Besides, electronic-based contact tracing solutions can be augmented by symptom self-reports gathered using electronic patient reported outcome (ePRO) platforms and by physiological data collected using wearable sensors. We performed a detailed assessment of 12 ePRO solutions, 27 wearable sensors, and 44 electronic-based contact tracing solutions. These technologies were evaluated using criteria developed to assess their suitability to address the COVID-19 pandemic. We identified a number of solutions that could augment if not provide a more effective alternative to manual contact tracing. Finally, we propose a theoretical framework in which ePRO platforms, wearable sensors, and electronic-based contact tracing solutions would be utilized in combination with molecular and serological tests to identify and isolate COVID-19 cases rapidly.", "qid": 33, "docid": "hz3z6xkk", "rank": 38, "score": 7.584499835968018}, {"content": "Title: Why Challenge Trials of SARS\u2010CoV\u20102 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Content: Human challenge trials to test the efficacy of vaccine candidates against SARS\u2010CoV\u20102, the novel coronavirus behind Covid\u201019, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid\u201019 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.", "qid": 33, "docid": "3059lhea", "rank": 39, "score": 7.5671000480651855}, {"content": "Title: Why Challenge Trials of SARS-CoV-2 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Content: Human challenge trials to test the efficacy of vaccine candidates against SARS-CoV-2, the novel coronavirus behind Covid-19, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid-19 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.", "qid": 33, "docid": "bd7f9mgj", "rank": 40, "score": 7.567099094390869}, {"content": "Title: How Close are We to a COVID-19 Vaccine? Content: This review provides an overview regarding the main aspects of candidate COVID-19 vaccines and pathophysiology of disease The types of biotechnological candidate vaccines to be developed against COVID-19, their degree of protection and the pathophysiological mechanism of the disease were analyzed in this review article The literature data on which cruxes for the development of biotechnological candidate vaccines to be wended are based was researched Data that could give reference to various biotechnological candidate vaccines were reviewed For this purpose, up-to-date literature data was utilized The ways to succeed in the development of a vaccine requiring a technological infrastructure are to synthesize the data obtained from long term trials and to put them into practice subsequently The vaccines to be developed by means of recombinant DNA technology will be a source of inspiration to people for further studies After a rapid process of vaccine development, the use of COVID-19 vaccine can be mainstreamed among people to prevent the disease As a result of these practices, the evaluation of which vaccine will be more safe, reliable and effective will be performed after phase studies", "qid": 33, "docid": "asw56fla", "rank": 41, "score": 7.564700126647949}, {"content": "Title: Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge Content: In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions. Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5\u00d7106 pfu) and medium (5\u00d7104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5\u00d7102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia on day 7 onwards. No obvious elevated temperature or signs of coughing or dyspnoea were observed although animals did present with a consistent post-viral fatigue lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.", "qid": 33, "docid": "08zf7161", "rank": 42, "score": 7.479499816894531}, {"content": "Title: Pharmacologicaltreatment of COVID-19: lights and shadows Content: At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.", "qid": 33, "docid": "o29773cz", "rank": 43, "score": 7.46750020980835}, {"content": "Title: Potential therapeutic agents against COVID-19: What we know so far Content: The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.", "qid": 33, "docid": "eitnkdi9", "rank": 44, "score": 7.444200038909912}, {"content": "Title: Neue Impfstoffe gegen Tuberkulose Content: With about 10 million active disease cases and 1.5 million deaths in 2018, tuberculosis (TB) remains one of the most threatening infectious diseases. Yet, the World Health Organization (WHO) aims to reduce morbidity and mortality by 90 and 95%, respectively, between 2015 and 2035. Although diagnostics, therapeutics, and a vaccine are available, it is beyond doubt that better intervention measures are needed to accomplish this ambitious goal. The vaccine bacille Calmette-Gu\u00e9rin (BCG) partially protects infants against TB, but it is virtually ineffective against pulmonary TB in adolescents and adults. The efficacy of this vaccine, however, has not yet been fully exploited. In addition, new vaccine candidates are currently being assessed in clinical trials. Because a quarter of all people are latently infected with Mycobacterium tuberculosis (Mtb), new vaccines must be applied not only prior to infection (pre-exposure vaccination) but also after infection (postexposure vaccination). Prevention of infection, prevention of disease, and prevention of recurrence are currently assessed as clinical endpoints. Because protection against TB is primarily mediated by T lymphocytes, TB vaccine development focuses on protective T cell responses. Protein adjuvant formulations, viral vectors, and killed and live bacterial vaccines are currently being assessed in clinical trials. Moreover, therapeutic vaccination is clinically tested, notably in adjunct to canonical drug therapy to multiresistant TB. It is likely that a single vaccine cannot accomplish the various indications and that different vaccination strategies are required.", "qid": 33, "docid": "bgehvxo7", "rank": 45, "score": 7.412899971008301}, {"content": "Title: Covid-19 Content: Contents / What is COVID-19? : Iwata, Kentaro;review:COVID-19 : Kutsuna, Satoshi ;Testing and diagnosis of COVID-19 : Uehara, Yuki ;Drugs listed as drug candidates for treatment of COVID-19 : Yamada, Kazunori ;Talking about COVID-19 : Iwata, Kentaro ;Front line of infection control : Iwata, Kentaro, Sakamoto, Fumie ;11 articles to learn about COVID19 : Kurahara, Yu ;COVID-19 infection control on February 25 : Iwata, Kentaro, Oka, Hideaki, Shibata, Ayako ;Inpatient response to COVID-19 : Iwata, Kentaro ;Why the Tokyo Olympics shouldn't be held in the summer of 2020 (and the decision to postpone it was right) : Iwata, Kentaro&nbsp;", "qid": 33, "docid": "m2d0m5oi", "rank": 46, "score": 7.40310001373291}, {"content": "Title: COVID-19 Vaccine Candidates: Prediction and Validation of 174 SARS-CoV-2 Epitopes Content: The recent outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested 19 epitope-HLA-binding prediction tools, and using an in vitro peptide MHC stability assay, we assessed 777 peptides that were predicted to be good binders across 11 MHC allotypes. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allotype in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA allotypes. Our findings may contribute to the design of an efficacious vaccine against COVID-19.", "qid": 33, "docid": "wxagjqbt", "rank": 47, "score": 7.402900218963623}, {"content": "Title: IgY - turning the page toward passive immunization in COVID-19 infection (Review) Content: The world is facing one of the major outbreaks of viral infection of the modern history, however, as vaccine development workflow is still tedious and can not control the infection spreading, researchers are turning to passive immunization as a good and quick alternative to treat and contain the spreading. Within passive immunization domain, raising specific immunoglobulin (Ig)Y against acute respiratory tract infection has been developing for more than 20 years. Far from being an obsolete chapter we will revise the IgY-technology as a new frontier for research and clinic. A wide range of IgY applications has been effectively confirmed in both human and animal health. The molecular particularities of IgY give them functional advantages recommending them as good candidates in this endeavor. Obtaining specific IgY is sustained by reliable and nature friendly methodology as an alternative for mammalian antibodies. The aria of application is continuously enlarging from bacterial and viral infections to tumor biology. Specific anti-viral IgY were previously tested in several designs, thus its worth pointing out that in the actual COVID-19 pandemic context, respiratory infections need an enlarged arsenal of therapeutic approaches and clearly the roles of IgY should be exploited in depth.", "qid": 33, "docid": "ite7s07f", "rank": 48, "score": 7.386600017547607}, {"content": "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review Content: Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.", "qid": 33, "docid": "m95bmi9t", "rank": 49, "score": 7.367000102996826}, {"content": "Title: Contingent assessment of the COVID-19 vaccine Content: The COVID-19 pandemic has not only had a negative impact on people's health and life behavior, but also on economies around the world. At the same time, laboratories and institutions are working hard to obtain a COVID-19 vaccine, which we hope will be available soon. However, there has been no assessment of whether an individual and society value \u00e2\u0080\u008b\u00e2\u0080\u008ba vaccine monetarily, and what factors determine this value. Therefore, the objective of this research was to estimate the individual's willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. For this, we used the contingent valuation approach, in its single and double-bounded dichotomous choice format, which was based on a hypothetical market for a vaccine. The sample used was obtained through an online survey of n = 566 individuals from Chile. The main results showed that the WTP depends on the preexistence of chronic disease (p&#8804;0.05), knowledge of COVID-19 (p&#8804;0.05), being sick with COVID-19 (p&#8804;0.05), perception of government performance (p&#8804;0.01), employment status (p&#8804;0.01), income (p&#8804;0.01), health care (p&#8804;0.05), adaptation to quarantine with children at home (p&#8804;0.01) and whether the person has recovered from COVID-19 (p&#8804;0.10). According to our discrete choice model in double-bounded dichotomous format, it was concluded that the individuals' WTP is US$184.72 (CI: 165.52-203.92; p < 0.01). This implies a social valuation of approximately US$2232 million, corresponding to 1.09% of the GNP per capita.", "qid": 33, "docid": "kqjp4y41", "rank": 50, "score": 7.332300186157227}, {"content": "Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.", "qid": 33, "docid": "svo94kuo", "rank": 51, "score": 7.314199924468994}, {"content": "Title: COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning Content: To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID-19), but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8\u201310) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and linear B-cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID-19 vaccine development.", "qid": 33, "docid": "ld0vo1rl", "rank": 52, "score": 7.283299922943115}, {"content": "Title: in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA Content: The recent pandemic of COVID19 that has struck the world is yet to be battled by a potential cure. Countless lives have been claimed due to the existing pandemic and the societal normalcy has been damaged permanently. As a result, it becomes crucial for academic researchers in the field of bioinformatics to combat the existing pandemic. The study involved collecting the virulent strain sequence of SARS-nCoV19 for the country USA against human host through publically available bioinformatics databases. Using in-silica analysis and reverse vaccinology, two leader proteins were identified to be potential vaccine candidates for development of a multi-epitope drug. The results of this study can provide further researchers better aspects and direction on developing vaccine and immune responses against COVID19. This work also aims at promoting the use of existing bioinformatics tools to faster streamline the pipeline of vaccine development. The Situation of COVID19 A new infection respiratory disease was first observed in the month of December 2019, in Wuhan, situated in the Hubei province, China. Studies have indicated that the reason of this disease was the emergence of a genetically-novel coronavirus closely related to SARS-CoV. This coronavirus, now named as nCoV-19, is the reason behind the spread of this fatal respiratory disease, now named as COVID-19. The initial group of infections is supposedly linked with the Huanan seafood market, most likely due to animal contact. Eventually, human-to-human interaction occurred and resulted in the transmission of the virus to humans. [13]. Since then, nCoV-19 has been rapidly spreading within China and other parts of World. At the time of writing this article (mid-March 2020), COVID-19 has spread across 146 countries. A count of 164,837 cases have been confirmed of being diagnosed with COVID-19, and a total of 6470 deaths have occurred. The cumulative cases have been depicting a rising trend and the numbers are just increasing. WHO has declared COVID-19 to be a \u201cglobal health emergency\u201d. [14]. Current Scenario and Objectives Currently, research is being conducted on a massive level to understand the immunology and genetic characteristics of the disease. However, no cure or vaccine of nCoV-19 has been developed at the time of writing this article. Though, nCoV-19 and SARS-CoV are almost genetically similar, the respiratory syndrome caused by both of them, COVID-19 and SARS respectively, are completely different. Studies have indicated that \u2013 \u201cSARS was more deadly but much less infectious than COVID-19\u201d. -World Health Organization", "qid": 33, "docid": "qbcb9qi3", "rank": 53, "score": 7.266600131988525}, {"content": "Title: A Scalable Topical Vectored Vaccine Candidate Against SARS-CoV-2 Content: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose a de novo synthesised avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of Newcastle disease virus, proto-type virus of AOaV-1, was engineered to express full length spike (S) glycoprotein which is highly neutralizing and major protective antigen of the SARS-CoV-2. Broad-scale in vitro characterization of recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagation in chicken embryonated eggs, and this expression did not significantly impact the in vitro growth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primates per se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.", "qid": 33, "docid": "v9ndmjzm", "rank": 54, "score": 7.252600193023682}, {"content": "Title: Contingent assessment of the COVID-19 vaccine Content: The COVID-19 pandemic has not only had a negative impact on people\u2019s health and life behavior, but also on economies around the world. At the same time, laboratories and institutions are working hard to obtain a COVID-19 vaccine, which we hope will be available soon. However, there has been no assessment of whether an individual and society value \u200b\u200ba vaccine monetarily, and what factors determine this value. Therefore, the objective of this research was to estimate the individual\u2019s willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. For this, we used the contingent valuation approach, in its single and double-bounded dichotomous choice format, which was based on a hypothetical market for a vaccine. The sample used was obtained through an online survey of n = 566 individuals from Chile. The main results showed that the WTP depends on the preexistence of chronic disease ([Formula: see text]), knowledge of COVID-19 ([Formula: see text]), being sick with COVID-19 ([Formula: see text]), perception of government performance ([Formula: see text]), employment status ([Formula: see text]), income ([Formula: see text]), health care ([Formula: see text]), adaptation to quarantine with children at home ([Formula: see text] and whether the person has recovered from COVID-19 ([Formula: see text]. According to our discrete choice model in double-bounded dichotomous format, it was concluded that the individuals\u2019 WTP is US$184.72 (CI: 165.52-203.92; p < 0.01). This implies a social valuation of approximately US$2,232 million, corresponding to 1.09% of the GNP per capita.", "qid": 33, "docid": "7b2mt1a8", "rank": 55, "score": 7.230899810791016}, {"content": "Title: Criticism of the Oxford Coronavirus Vaccine Content: This piece at Forbes by Bill Haseltine has set off a lot of comment \u2013 it\u2019s a look at the Oxford group\u2019s vaccine candidate as compared to the SinoVac candidate, and you may recall (background here) that these are the two teams that have separately reported that their vaccines appear to protect rhesus monkeys from infection after exposure to the coronavirus Haseltine has some criticisms of the Oxford data, and as you will see from that link to his name, his opinions deserve to be taken seriously So what\u2019s going on? Update: here\u2019s the take on this at BioCentury Looking at the preprint on the Oxford results, Haseltine has a problem with the claim that the monkeys were protected from infection by a dose of ChAdOx1 nCoV-19 The key data are in the preprint\u2019s Figure 3 The Oxford team checked for viral RNA several different ways One was using bronchoaveolar lavage (BAL fluid), a sampling technique that involves running a bronchoscope down into the lungs and washing out aveolar spaces \u2013 a pretty darn invasive assay, which is why you don\u2019t hear about it all that much compared to the still-not-so-nonivasive nose swabs BAL fluid of the virus-exposed unvaccinated animals showed coronavirus genomic RNA throughout the study, and viral subgenomic RNA (more indicative of active replication) at days 3 and 5 after exposure Meanwhile, the vaccinated animals showed the genomic RNA in only two monkeys, and no subgenomic RNA at all", "qid": 33, "docid": "wi5wnizu", "rank": 56, "score": 7.224100112915039}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 33, "docid": "8lktpcda", "rank": 57, "score": 7.220799922943115}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 33, "docid": "d2j9wpqk", "rank": 58, "score": 7.220798969268799}, {"content": "Title: COVID-19 vaccines move toward clinic Content: Drug developers are moving their experimental vaccines for COVID-19 into clinical trials at a frenetic pace Trials for five such vaccines have begun in China Two are being tested in the US, with a third slated to start this month And trials of two more are due to begin in the UK and Australia in the coming weeks \u201cEverything from basic science to clinical science is progressing at a pace faster than ever before\u2014and very appropriately, given the grave nature of the current global crisis,\u201d says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center The World Health Organization says at least 70 COVID-19 vaccines are in development, while scientists at the Coalition for Epidemic Preparedness Innovations (CEPI) have counted 115 Moderna was the first to begin clinical testing of a COVID-19 vaccine, just 66 days after downloading the genome of SARS-CoV-2,", "qid": 33, "docid": "y2bylnte", "rank": 59, "score": 7.172699928283691}, {"content": "Title: SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward Content: The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to \"normal.\" Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.", "qid": 33, "docid": "jwa2gkb9", "rank": 60, "score": 7.15749979019165}, {"content": "Title: SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward Content: The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to \u201cnormal.\u201d Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.", "qid": 33, "docid": "vqim4t6x", "rank": 61, "score": 7.157498836517334}, {"content": "Title: Development of an inactivated vaccine candidate for SARS-CoV-2 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.", "qid": 33, "docid": "5bftuzw5", "rank": 62, "score": 7.1519999504089355}, {"content": "Title: [At least 68 vaccine candidates under development]. Content: The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.", "qid": 33, "docid": "l9l6z1o0", "rank": 63, "score": 7.145599842071533}, {"content": "Title: An overview on COVID-19: reality and expectation Content: Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO\u2019s strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions.", "qid": 33, "docid": "ino9srb6", "rank": 64, "score": 7.137400150299072}, {"content": "Title: [Coronavirus, emerging viruses]. Content: Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.", "qid": 33, "docid": "xkzvzonj", "rank": 65, "score": 7.128600120544434}, {"content": "Title: Vaccines for COVID-19: the current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 \u2013 the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 33, "docid": "ievuxa6k", "rank": 66, "score": 7.121799945831299}, {"content": "Title: Vaccines for COVID-19: The current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 33, "docid": "o8bkorjn", "rank": 67, "score": 7.121798992156982}, {"content": "Title: Elucidation on the Physicochemical Properties of Potential and Clinically Approved Antiviral Drugs: A Search for Effective Therapies against SARS-CoV-2 Infection Content: COVID-19 has been confirmed in millions of individuals worldwide, rendering it a global medical emergency In the absence of vaccines and the unavailability of effective drugs for the SARS-CoV-2 infection, vaccine development is being continuously explored and several antiviral compounds and immunotherapies are currently being investigated Given the high similarity in genetic identity between SARS-CoV and SARS-CoV-2, the present investigation identified the interaction between the physicochemical properties and the antiviral activity of different potential and clinically approved antiviral drugs against SARS-CoV using hierarchically weighted principal component analysis Representative drugs from the classes of neuraminidase inhibitors, reverse transcriptase inhibitors, protease inhibitors, nucleoside analogues, and other compounds with potential antiviral activity were examined The pharmacologic classification and the biological activity of the different antiviral drugs were described using indices, namely, rotatable bond count, molecular weight, heavy atom count, and molecular complexity (92 32% contribution rate) The physicochemical properties and inhibitory action against SARS-CoV-2 of lopinavir, chloroquine, ivermectin, and ciclesonide validated the adequacy of the current computational approach The findings of the present study provide additional information, although further investigation is warranted to identify potential targets and establish exact mechanisms, in the emergent search and design of antiviral drug candidates and their subsequent synthesis as effective therapies for COVID-19", "qid": 33, "docid": "s10iv1jg", "rank": 68, "score": 7.092400074005127}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 33, "docid": "rirzes0m", "rank": 69, "score": 7.0782999992370605}, {"content": "Title: Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria Content: BACKGROUND: Vaccines are the most reliable alternative to elicit sterile immunity against malaria but their development has been hindered by polymorphisms and strain-specificity in previously studied antigens. New vaccine candidates are therefore urgently needed. Highly conserved Plasmodium falciparum reticulocyte-binding protein homologue-5 (PfRH5) has been identified as a potential candidate for anti-disease vaccine development. PfRH5 is essential for erythrocyte invasion by merozoites and crucial for parasite survival. However, there is paucity of data on the extent of genetic variations on PfRH5 in field isolates of Plasmodium falciparum. This study described genetic polymorphisms at the high affinity binding polypeptides (HABPs) 36718, 36727, 36728 of PfRH5 in Nigerian isolates of P. falciparum. This study tested the hypothesis that only specific conserved B and T cell epitopes on PfRH5 HABPs are crucial for vaccine development. METHODS: One hundred and ninety-five microscopically confirmed P. falciparum samples collected in a prospective cross-sectional study of three different populations in Lagos, Nigeria. Genetic diversity and haplotype construct of Pfrh5 gene were determined using bi-directional sequencing approach. Tajima\u2019s D and the ratio of nonsynonymous vs synonymous mutations were utilized to estimate the extent of balancing and directional selection in the pfrh5 gene. RESULTS: Sequence analysis revealed three haplotypes of PfRH5 with negative Tajima\u2019s D and dN/dS value of \u2212 1.717 and 0.011 \u00b1 0.020, respectively. A single nucleotide polymorphism, SNP (G \u2192 A) at position 608 was observed, which resulted in a change of the amino acid cysteine at position 203 to tyrosine. Haplotype and nucleotide diversities were 0.318 \u00b1 0.016 and 0.0046 \u00b1 0.0001 while inter-population genetic differentiation ranged from 0.007 to 0.037. Five polypeptide variants were identified, the most frequent being KTKYH with a frequency of 51.3%. One B-cell epitope, 151 major histocompatibility complex (MHC) class II T-cell epitopes, four intrinsically unstructured regions (IURs) and six MHC class I T-cell epitopes were observed in the study. Phylogenetic analysis of the sequences showed clustering and evidence of evolutionary relationship with 3D7, PAS-2 and FCB-2 RH5 sequences. CONCLUSIONS: This study has revealed low level of genetic polymorphisms in PfRH5 antigen with B- and T-cell epitopes in intrinsically unstructured regions along the PfRH5 gene in Lagos, Nigeria. A broader investigation is however required in other parts of the country to support the possible inclusion of PfRH5 in a cross-protective multi-component vaccine.", "qid": 33, "docid": "7bpeszm5", "rank": 70, "score": 7.077199935913086}, {"content": "Title: TB Prevalence Correlation to Covid- 19 Mortality Content: TB Prevalence Correlation to Covid- 19 Mortality Tareef Fadhil Raham * Abstract Back ground : Latent TB disease reflect a state of persistent immune response to stimulation by Mycobacterium tuberculois . TB infection lead to latent TB disease in 90-95 % while 5-10 % of individuals develop active TB disease when compared to BCG , BCG is 60% effective against the development of active TB. Studies done to test association of BCG with covid-19 morbidity and mortality and it was thought that BCG have preventive effects due to presumed non specific anti viral effects in this study we test association between prevalent of TB which reflects about 90-95 % of corresponding latent TB infection with covid 19 mortality. Materials and methods : countries divided into 5 groups according to BCG following status : No vaccination at all no previous BCG group , no current but had BCG in past (one or more), 1 current BCG with previous booster (s) , just 1 BCG now no previous booster (s) and more than 1 BCG setting now. covid -19 deaths taken as it is on these are tested against TB prevalence 2018. Results: Slop values have significant influences between TB prevalence and covid -19 deaths among all tested groups and are reversed in just 1 BCG now no previous booster (s) group P<0.01 coefficient (0.30751) ,1 current BCG with previous booster (s) P<0.01 coefficient (0.63662) , and more than 1 BCG setting now group P<0.05 with coefficient of (0.61580). While no vaccination at all no previous BCG group shows Compound model linear regression P<0.05 coefficient ( 97.45%)and No current but had BCG in past (one or more) group shows Cubic model P<0.01, coefficient (66.098%) The overall slope value is highly significant and reverse influence at P<0.01, as well as highly significant relationship coefficient (0.36749). The linear regression model obtained in logarithmic mode for all tested sample and being inverse in countries with more than 1 BCG setting at this time and countries with 1 current BCG with previous booster (s) furthermore linear regression model is logarithmic in countries with just 1 BCG now and no previous booster (s) . Conclusion: TB prevalence is strongly associated with covid-19 mortality and being more sever in absence of BCG vaccine . Recommendations: Early interventions might be considered based on the supportive evidence at this timewhich include BCG vaccination ,review of current latent TB programs. Key words :TB prevalence, covid- 19 mortality ,BCG * consultant pediatrician ; DCH and Arabic Board;MOH Iraq tareeffadhil@yahoo.com (00964)7901584338", "qid": 33, "docid": "sp5irqp8", "rank": 71, "score": 7.070300102233887}, {"content": "Title: SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts Content: Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an excellent species to study mild/subclinical COVID-19 disease and have shed light on unknown aspects of long-term virus shedding. They are ideally suited for preclinical evaluation of candidate vaccines and therapeutic interventions. One Sentence Summary Subclinical infection of African green monkeys infected with SARS-CoV-2 results in prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts.", "qid": 33, "docid": "z225s2fc", "rank": 72, "score": 7.055300235748291}, {"content": "Title: Immunogenicity of a DNA vaccine candidate for COVID-19 Content: The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.", "qid": 33, "docid": "f5xs0tv2", "rank": 73, "score": 7.055200099945068}, {"content": "Title: Adjusting Coronavirus prevalence estimates for laboratory test kit error Content: Testing representative populations to determine the prevalence or percent of the population with active SARS-Cov-2 (COVID-19) infection and/or antibodies to infection is being recommended as essential for making public policy decisions to open-up or to continue enforcing national, state and local government rules to shelter-in-place. However, all laboratory tests are imperfect and have estimates of sensitivity and specificity less than 100% - in some cases considerably less than 100%. That error will lead to biased prevalence estimates. If the true prevalence of COVID-19 is low, possibly in the range of 1-5%, then testing error will lead to a constant background of bias that will most likely be larger and possibly much larger than the true prevalence itself. As a result, what is needed is a method for adjusting prevalence estimates for testing error. In this paper we outline methods for adjusting prevalence estimates for testing error both prospectively in studies being planned and retrospectively in studies that have been conducted. The methods if employed would also help to harmonize study results within countries and around the world. Adjustment can lead to more accurate prevalence estimates and to better policy decisions.", "qid": 33, "docid": "1xjgtj0t", "rank": 74, "score": 7.047599792480469}, {"content": "Title: A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate Content: The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.", "qid": 33, "docid": "zwsvlnwe", "rank": 75, "score": 7.044300079345703}, {"content": "Title: COVID-19 Comes 40 Years After AIDS - Any Lesson? Content: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has hit health-care systems and societies in an unprecedented manner. In 1981, the first cases of AIDS were reported and wide diagnostic testing helped to characterize high-risk groups and the global burden of the epidemic. With Coronavirus Disease (COVID)-19, everything has happened too fast and both cases and fatalities are huge but still uncertain in most places. Diagnostic testing of active and past SARS-CoV-2 infections needs to expand rapidly, ideally using rapid tests. COVID-19 deaths are highly concentrated in the elderly population, with a large proportion of fatalities being \"with\" rather than \"by\" SARS-CoV-2 infection. They are often the result of inadequate health care due to overwhelming demands. To date, there is no specific therapy for SARS-CoV-2 infection. Several antivirals are being tested clinically, including remdesivir, at this time the most promising. For others such as lopinavir/ritonavir, neither significant virological nor clinical benefit has been shown. Given the characteristic pulmonary cytokine storm underlying the pathogenic mechanism of severe COVID-19 pneumonia and acute respiratory distress, antiinflammatory agents are being investigated. The benefit of orticosteroids, hydroxychloroquine, etc., is limited. Monoclonal antibodies targeting different pro-inflammatory cytokines, such as tocilizumab, an anti-interleukin 6 agent, are being tried with encouraging results. Ultimately a protective vaccine will be the best response for controlling the COVID-19 pandemic.", "qid": 33, "docid": "asapvflf", "rank": 76, "score": 7.042600154876709}, {"content": "Title: Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening Content: Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \"up\" to \"down\" conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "qid": 33, "docid": "5vgfliv0", "rank": 77, "score": 7.034599781036377}, {"content": "Title: Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening Content: Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \u201cup\u201d to \u201cdown\u201d conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below \u20138.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "qid": 33, "docid": "74xvvwrw", "rank": 78, "score": 7.0345988273620605}, {"content": "Title: Novel Coronavirus (nCoV): a Bitter Old Enemy in a New Avatar Content: Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.", "qid": 33, "docid": "1ij25a7u", "rank": 79, "score": 7.02269983291626}, {"content": "Title: Vaccination against the Epstein\u2013Barr virus Content: Epstein\u2013Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be able to prevent symptomatic primary infection, the most likely EBV-associated pathology against which EBV vaccines will be initially tested. Thus, the variety of EBV vaccines reflects the sophisticated life cycle of this human tumor virus and only vaccination in humans will finally be able to reveal the efficacy of these candidates. Nevertheless, the recently renewed efforts to develop an EBV vaccine and the long history of safe adoptive T cell transfer to treat EBV-associated malignancies suggest that this oncogenic \u03b3-herpesvirus can be targeted by immunotherapies. Such vaccination should ideally implement the very same immune control that protects healthy EBV carriers.", "qid": 33, "docid": "t3eeks1n", "rank": 80, "score": 7.0065999031066895}, {"content": "Title: Ethical considerations for epidemic vaccine trials Content: Vaccines are a powerful measure to protect the health of individuals and to combat outbreaks such as the COVID-19 pandemic. An ethical dilemma arises when one effective vaccine has been successfully developed against an epidemic disease and researchers seek to test the efficacy of another vaccine for the same pathogen in clinical trials involving human subjects. On the one hand, there are compelling reasons why it would be unethical to trial a novel vaccine when an effective product exists already. First, it is a firm principle of medical ethics that an effective treatment or vaccine should not be withheld from patients if their life may depend on it. Second, since epidemic outbreaks often emerge in settings with less-resourced health systems, there is a pronounced risk that any trial withholding an effective vaccine would disproportionately affect the vulnerable populations that historically have been exploited for biomedical research. Third, clinical trials for novel vaccines may be at odds with efforts to control active outbreaks. On the other hand, it may be justified to conduct a trial for a candidate vaccine if it is expected to have certain advantages compared with the existing product. This essay discusses key factors for comparing vaccines against epidemic pathogens, including immunological, logistical and economic considerations. Alongside a case study of the development of vaccines for Ebola, the essay seeks to establish a general framework that should be expanded and populated by immunologists, epidemiologists, economists and bioethicists, and ultimately could be applied to the case of COVID-19 vaccines.", "qid": 33, "docid": "fzbu506l", "rank": 81, "score": 7.001299858093262}, {"content": "Title: A SARS-CoV-2 vaccine candidate: In silico cloning and validation Content: SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.", "qid": 33, "docid": "du2zxq96", "rank": 82, "score": 6.992000102996826}, {"content": "Title: At the heart of COVID-19. Content: Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.", "qid": 33, "docid": "6wy9y2f0", "rank": 83, "score": 6.985199928283691}, {"content": "Title: At the heart of COVID-19 Content: Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.", "qid": 33, "docid": "z3esk2dk", "rank": 84, "score": 6.985198974609375}, {"content": "Title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform Content: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "qid": 33, "docid": "48knj0tm", "rank": 85, "score": 6.977399826049805}, {"content": "Title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform Content: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS- CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. UISS is then potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "qid": 33, "docid": "71n1tgrw", "rank": 86, "score": 6.977398872375488}, {"content": "Title: Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach Content: Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.", "qid": 33, "docid": "1ir19s25", "rank": 87, "score": 6.969900131225586}, {"content": "Title: A recombinant rabies vaccine expressing the trimeric form of the glycoprotein confers enhanced immunogenicity and protection in outbred mice. Content: Rabies is a disease characterized by an invariably lethal encephalitis of viral origin that can be controlled by preventive vaccination programs of wildlife, domestic animals and humans in areas with a high risk of exposure. Currently available vaccines are expensive, cumbersome to produce and require intensive immunization and booster schemes to induce and maintain protective immunity. In the present study, we describe the development of candidate recombinant subunit rabies vaccines based on the glycoprotein G of the prototype rabies virus (RABV-G) expressed either as a monomer (RABV-mG) or in its native trimeric configuration (RABV-tG), with or without Matrix-M\u2122 adjuvant. Immunogenicity and protective efficacy of the respective candidate vaccines were tested in outbred NIH Swiss albino mice. The RABV-tG candidate vaccine proved to be superior to the RABV-mG vaccine candidate both in terms of immunogenicity and efficacy. The relatively poor immunogenicity of the RABV-mG vaccine candidate was greatly improved by the addition of the adjuvant. A single, low dose of RABV-tG in combination with Matrix-M\u2122 induced high levels of high avidity neutralizing antibodies and protected all mice against challenge with a lethal dose of RABV. Consequently RABV-tG used in combination with Matrix-M\u2122 is a promising vaccine candidate that overcomes the limitations of currently used vaccines.", "qid": 33, "docid": "nkq39uo1", "rank": 88, "score": 6.9644999504089355}, {"content": "Title: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.", "qid": 33, "docid": "safr9z37", "rank": 89, "score": 6.9232001304626465}, {"content": "Title: SARS-CoV-2: A New Song Recalls an Old Melody Content: The viruses causing the SARS outbreak of 2002-2003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation.", "qid": 33, "docid": "ymoigqdw", "rank": 90, "score": 6.919000148773193}, {"content": "Title: SARS-CoV-2: A New Song Recalls an Old Melody Content: The viruses causing the SARS outbreak of 2002\u20132003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation.", "qid": 33, "docid": "znx5p3yp", "rank": 91, "score": 6.918999195098877}, {"content": "Title: Pandemic Best Regulatory Practices: An Urgent Need in the COVID-19 Pandemic Content: As large numbers of candidate drugs and vaccines for potential use in the coronavirus disease 2019 (COVID-19) pandemic are being investigated, medicine regulators globally must now make urgent, informed, contextually risk-based decisions regarding clinical trials and marketing authorizations. They must do this with the flexibility demanded by the pandemic while maintaining their core risk assessment and public safety functions. We lay out the critical role of regulators in the current crisis and offer eight \"pandemic best regulatory practices.\" These should support both the regulatory public heath imperative and assure timely patient access to effective, safe, quality products worldwide during this emergency-thus contributing to ending this pandemic as quickly, effectively, and safely as possible.", "qid": 33, "docid": "m95t84yz", "rank": 92, "score": 6.88640022277832}, {"content": "Title: A review on possible modes of action of chloroquine/hydroxychloroquine: repurposing against SAR-CoV-2 (COVID-19) pandemic Content: Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.", "qid": 33, "docid": "4qmeylme", "rank": 93, "score": 6.884799957275391}, {"content": "Title: Testing for tracing or testing just for treating? A comparative analysis between strategies to face COVID-19 pandemic. Content: There is some consensus in Europe and Asia about testing rates being crucial to controlling COVID-19 pandemics. There are though misconceptions on what means an effective high testing rate. This paper demonstrates that the rate of tests per detected case (Tests/Case) is the important variable, correlating negatively with the number of deaths. The higher the Tests/Case rate, the lower the death rate, as this predictor is causally related to contact tracing and isolation of the vectors of the disease. Doubling Tests/Case typically divides by three the number of deaths. On the other hand, per capita testing rate is a poor predictor for the performance of policies to fight the pandemics. The number of tests per 1,000 inhabitants (Tests/1,000) tends to correlate positively with the number of deaths. In some cases, high levels of Tests/1,000 just mean an epidemic that ran out of control, with an explosion of cases that demands high testing rates just to confirm the diagnosis of the very sick.", "qid": 33, "docid": "rjzther1", "rank": 94, "score": 6.880199909210205}, {"content": "Title: Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study Content: At present, novel Coronavirus (2019-nCoV, the causative agent of COVID-19) has caused worldwide social and economic disruption. The disturbing statistics of this infection promoted us to develop an effective vaccine candidate against the COVID-19. In this study, bioinformatics approaches were employed to design and introduce a novel multi-epitope vaccine against 2019-nCoV that can potentially trigger both CD(4+) and CD(8+) T-cell immune responses and investigated its biological activities by computational tools. Three known antigenic proteins (Nucleocapsid, ORF3a, and Membrane protein, hereafter called NOM) from the virus were selected and analyzed for prediction of the potential immunogenic B and T-cell epitopes and then validated using bioinformatics tools. Based on in silico analysis, we have constructed a multi-epitope vaccine candidate (NOM) with five rich-epitopes domain including highly scored T and B-cell epitopes. After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A*11:01. In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A*11:01 receptors. MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Communicated by Ramaswamy H. Sarma", "qid": 33, "docid": "c5uesg6p", "rank": 95, "score": 6.876100063323975}, {"content": "Title: Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study Content: At present, novel Coronavirus (2019-nCoV, the causative agent of COVID-19) has caused worldwide social and economic disruption. The disturbing statistics of this infection promoted us to develop an effective vaccine candidate against the COVID-19. In this study, bioinformatics approaches were employed to design and introduce a novel multi-epitope vaccine against 2019-nCoV that can potentially trigger both CD4+ and CD8+ T-cell immune responses and investigated its biological activities by computational tools. Three known antigenic proteins (Nucleocapsid, ORF3a, and Membrane protein, hereafter called NOM) from the virus were selected and analyzed for prediction of the potential immunogenic B and T-cell epitopes and then validated using bioinformatics tools. Based on in silico analysis, we have constructed a multi-epitope vaccine candidate (NOM) with five rich-epitopes domain including highly scored T and B-cell epitopes. After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A*11:01. In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A*11:01 receptors. MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Communicated by Ramaswamy H. Sarma.", "qid": 33, "docid": "rwtv6yys", "rank": 96, "score": 6.876099109649658}, {"content": "Title: Microstructure, pathophysiology and potential therapeutics of COVID-19: A comprehensive review Content: There have been over 7 million cases and almost 413,372 deaths globally due to the novel coronavirus (2019-nCoV) associated disease COVID-19, as of June 11, 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between the spike protein of 2019-nCoV and that of SARS-CoV are known to be around 76-78% and 73-76% for whole protein and receptor-binding domain (RBD), respectively. Thus, they have the potential to serve as drug and/ or vaccine candidate. However, the individual response against 2019-nCoV differs due to genetic variations in the human population. Understanding the variations in Angiotensin-converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019-nCoV infection could help in identifying individuals at higher risk from the COVID-19. A number of potential drugs/vaccines as well as antibody/cytokine-based therapeutics are running in various developmental stages of preclinical/clinical trials against SARS-CoV, MERS-CoV and 2019-nCoV with substantial cross-reactivity, which may be used against COVID-19. For diagnosis, reverse transcription polymerase chain reaction (RT-PCR) is the gold standard test for initial diagnosis of COVID-19. Kit based on serological tests are also recommended for investigating the spread of COVID-19 but it is challenging due to antibodies cross-reactivity. This review comprehensively summarizes the recent reports available regarding the host-pathogen interaction, morphological and genomic structure of the virus, and the diagnostic techniques as well as available and potential therapeutics against COVID-19. This article is protected by copyright. All rights reserved.", "qid": 33, "docid": "ma4cet3z", "rank": 97, "score": 6.869200229644775}, {"content": "Title: Microstructure, pathophysiology and potential therapeutics of COVID\u201019: A comprehensive review Content: There have been over 7 million cases and almost 413,372 deaths globally due to the novel coronavirus (2019\u2010nCoV) associated disease COVID\u201019, as of June 11, 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between the spike protein of 2019\u2010nCoV and that of SARS\u2010CoV are known to be around 76\u201078% and 73\u201076% for whole protein and receptor\u2010binding domain (RBD), respectively. Thus, they have the potential to serve as drug and/ or vaccine candidate. However, the individual response against 2019\u2010nCoV differs due to genetic variations in the human population. Understanding the variations in Angiotensin\u2010converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019\u2010nCoV infection could help in identifying individuals at higher risk from the COVID\u201019. A number of potential drugs/vaccines as well as antibody/cytokine\u2010based therapeutics are running in various developmental stages of preclinical/clinical trials against SARS\u2010CoV, MERS\u2010CoV and 2019\u2010nCoV with substantial cross\u2010reactivity, which may be used against COVID\u201019. For diagnosis, reverse transcription polymerase chain reaction (RT\u2010PCR) is the gold standard test for initial diagnosis of COVID\u201019. Kit based on serological tests are also recommended for investigating the spread of COVID\u201019 but it is challenging due to antibodies cross\u2010reactivity. This review comprehensively summarizes the recent reports available regarding the host\u2010pathogen interaction, morphological and genomic structure of the virus, and the diagnostic techniques as well as available and potential therapeutics against COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 33, "docid": "tsrvt356", "rank": 98, "score": 6.869199275970459}, {"content": "Title: A Highly Immunogenic Measles Virus-based Th1-biased COVID-19 Vaccine Content: The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. Author Contributions CH performed research, analyzed data, and wrote the paper; CS performed research and analyzed data; AA performed research and analyzed data; AE performed research and analyzed data; SM performed research, analyzed data, and wrote the paper; MH developed the bioinformatics pipeline and analyzed data; BS contributed new reagents and concepts; MDM designed and supervised research, analyzed data and wrote the paper; all authors read, corrected and approved the final manuscript. Significance Statement The COVID-19 pandemic has caused hundreds of thousands of deaths, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody-dependent enhancement or enhanced respiratory disease is rather unlikely. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats.", "qid": 33, "docid": "wc41epnv", "rank": 99, "score": 6.86899995803833}, {"content": "Title: Emerging Pharmaceutical Treatments of Novel COVID-19: A Review Content: As a new decade began, COVID-19 quickly gained importance as it became the cause of the current global pandemic. Research has been focusing on studying the structure of SARS-CoV-2 and investigates possible pharmaceutical approaches. With the number of cases increasing every day, globally, multiple drugs are being researched as possible candidates. Although multiple drugs show promise in the treatment of COVID-19 via either inhibiting viral replication or preventing fusion of the virus to the ACE2 receptors, further investigation is still warranted and necessary before the admission of any type of pharmaceutical agent. Furthermore, several supplements have also been documented in being utilized as treatment of COVID-19. The exact mechanism and efficacy of current candidate drugs are still being explored through clinical trials. Despite the advancements in current research with emerging treatments, social distancing and engaging in preventative measures remains crucial to attempt to prevent the occurrence of more cases and deaths, worldwide. This review explores various drugs and their mechanism of action which are either currently being used in clinical trials or may be used in the future for the treatment of COVID-19.", "qid": 33, "docid": "gl573ip9", "rank": 100, "score": 6.866399765014648}]}
{"query": "What are the longer-term complications of those who recover from COVID-19?", "hits": [{"content": "Title: Intervention Serology and Interaction Substitution: Modeling the Role of \u2018Shield Immunity\u2019 in Reducing COVID-19 Epidemic Spread Content: The COVID-19 pandemic has precipitated a global crisis, with more than 690,000 confirmed cases and more than 33,000 confirmed deaths globally as of March 30, 2020 [1\u20134]. At present twOfficentral public health control strategies have emerged: mitigation and suppression (e.g, [5]). Both strategies focus on reducing new infections by reducing interactions (and both raise questions of sustainability and long-term tactics). Complementary to those approaches, here we develop and analyze an epidemiological intervention model that leverages serological tests [6, 7] to identify and deploy recovered individuals as focal points for sustaining safer interactions via interaction substitution, i.e., to develop what we term \u2018shield immunity\u2019 at the population scale. Recovered individuals, in the present context, represent those who have developed protective, antibodies to SARS-CoV-2 and are no longer shedding virus [8]. The objective of a shield immunity strategy is to help sustain the interactions necessary for the functioning of essential goods and services (including but not limited to tending to the elderly [9], hospital care, schools, and food supply) while decreasing the probability of transmission during such essential interactions. We show that a shield immunity approach may significantly reduce the length and reduce the overall burden of an outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well recognized roles in estimating prevalence [10, 11] and in the potential development of plasma-based therapies [12\u201315].", "qid": 34, "docid": "drj3al9t", "rank": 1, "score": 12.207300186157227}, {"content": "Title: A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin Content: Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.", "qid": 34, "docid": "rhoo2k3r", "rank": 2, "score": 11.178999900817871}, {"content": "Title: Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis Content: Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.", "qid": 34, "docid": "tsd6sjcx", "rank": 3, "score": 10.737099647521973}, {"content": "Title: Recovering from the COVID-19 Pandemic: A Focus on Older Adults Content: As we look toward recovery from the COVID-19 pandemic, we overview challenges to be minimized, including economic setbacks, health and well-being effects, and highlighted ageism, racism, and classism. We articulate opportunities to be seized, including increased comfort with technology and online platforms; stronger family and intergenerational connections, renewed energy to combat social isolation; more respect for self-care and time management; increased awareness about the importance of advance directives; and, potentially, increased interest across disciplines to work on issues of aging society. Ongoing efforts to improve policies and programs for longer, healthier lives might now be more productive, as we communicate to consumers, public officials, and everyday citizens who may be more aware of what isn't working, what is at stake, and what might be improved.", "qid": 34, "docid": "i1wkv6bq", "rank": 4, "score": 10.706700325012207}, {"content": "Title: Recovering from the COVID-19 Pandemic: A Focus on Older Adults. Content: As we look toward recovery from the COVID-19 pandemic, we overview challenges to be minimized, including economic setbacks, health and well-being effects, and highlighted ageism, racism, and classism. We articulate opportunities to be seized, including increased comfort with technology and online platforms; stronger family and intergenerational connections, renewed energy to combat social isolation; more respect for self-care and time management; increased awareness about the importance of advance directives; and, potentially, increased interest across disciplines to work on issues of aging society. Ongoing efforts to improve policies and programs for longer, healthier lives might now be more productive, as we communicate to consumers, public officials, and everyday citizens who may be more aware of what isn't working, what is at stake, and what might be improved.", "qid": 34, "docid": "i25su8kc", "rank": 5, "score": 10.70669937133789}, {"content": "Title: What are the functional results and complications from allograft reconstruction after partial hemipelvectomy of the pubis? Content: BACKGROUND In patients undergoing hemipelvectomies including resection either of a portion of the pubis or the entire pubis from the symphysis to the lateral margin of the obturator foramen while sparing the hip (so-called Dunham Type III hemipelvectomies), reconstructions typically are not performed given the preserved continuity of the weightbearing axis and the potential complications associated with reconstruction. Allograft reconstruction of the pelvic ring may, however, offer benefits for soft tissue reconstruction of the pelvic floor and hip stability, but little is known about these reconstructions. QUESTIONS/PURPOSES (1) What is the postoperative functional status after allograft reconstruction of Type III pelvic defects? (2) What are the rates of hernia, infection, and hip instability? METHODS In this case series, we reviewed all patients with Type III pelvic resections (with or without anterior acetabular wall resections) who underwent allograft reconstruction between 2005 and 2013 at one center (N = 14). During the period in question, reconstruction was the general approach used in patients undergoing these resections; during that time, three other patients were treated without reconstruction as a result of either surgeon preference or the patient choosing to not have reconstruction after a discussion of the risks and benefits. Of the 14 patients treated with reconstruction, complete followup was available at a minimum of 1 year in 11 (other than those who died before the end of the first year; median, 19 months; range 16-70 months among those surviving), one was lost to followup before a year, and two others had partial telephone or email followup. Patient demographics, disease status, functional status, and complications were recorded. For a portion of the cohort (four patients) later in the series, we used a novel technique for anterior acetabular wall reconstruction using the concave cartilaginous surface of a proximal fibula allograft; the others received either a long bone (humerus or femur) or hemipelvis graft. Seven patients died of disease; two had local recurrence, and five died of metastatic disease. RESULTS All patients remained ambulatory Pain at 12 months after surgery was reported as none in five, mild in two, moderate in two, and severe in one. Operative complications included infection in two, symptomatic hernia in one, hip instability in one, dislocated total hip arthroplasty on the first postoperative day in one, and graft failure in one. CONCLUSIONS Allograft reconstruction after Type III pelvic resections can provide functional reconstruction of the pelvic ring, pelvic floor, and, in certain patients with partial anterior acetabular resections, the resected anterior acetabulum. This has implications in preventing the occurrence of hernia and hip instability in this patient population that is classically not reconstructed, although longer-term outcomes in a larger number of patients would help to better delineate this because infection, hernia, hip instability, and graft nonunion still remain concerns with this approach. The most important unanswered question remains whether, on balance, any benefits that may accrue to these patients as the result of reconstruction are offset by a relatively high likelihood of undergoing secondary or revision surgery.", "qid": 34, "docid": "ziyo5umz", "rank": 6, "score": 10.607999801635742}, {"content": "Title: Behavioral Health and Response for COVID-19 Content: Research from financial stress, disasters, pandemics, and other extreme events, suggests that behavioral health will suffer, including anxiety, depression, and posttraumatic stress symptoms. Furthermore, these symptoms are likely to exacerbate alcohol or drug use, especially for those vulnerable to relapse. The nature of coronavirus disease 2019 (COVID-19) and vast reach of the virus, leave many unknows for the repercussions on behavioral health, yet existing research suggests that behavioral health concerns should take a primary role in response to the pandemic. We propose a 4-step services system designed for implementation with a variety of different groups and reserves limited clinical services for the most extreme reactions. While we can expect symptoms to remit overtime, many will also have longer-term or more severe concerns. Behavioral health interventions will likely need to change overtime and different types of interventions should be considered for different target groups, such as for those who recover from COVID-19, health-care professionals, and essential personnel; and the general public either due to loss of loved ones or significant life disruption. The important thing is to have a systematic plan to support behavioral health and to engage citizens in prevention and doing their part in recovery by staying home and protecting others.", "qid": 34, "docid": "8kp07f7i", "rank": 7, "score": 10.604599952697754}, {"content": "Title: Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study Content: BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by \u03c7(2) test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, \u03c7(2) = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, \u03c7(2) = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, \u03c7(2) = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] \u00d710(9)/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] \u00d710(9)/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] \u03bcmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, \u03c7(2) = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, \u03c7(2) = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, \u03c7(2) = 23.257, P < 0.001), shock (11.9% vs. 0%, \u03c7(2) = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, \u03c7(2) = 7.655, P = 0.006). CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.", "qid": 34, "docid": "pby3i6wq", "rank": 8, "score": 10.083000183105469}, {"content": "Title: Significance of prophylactic intra-abdominal drain placement after laparoscopic distal gastrectomy for gastric cancer. Content: BACKGROUND Unnecessary intra-abdominal drain insertion must be avoided, but little is known about the value of prophylactic drainage following laparoscopic distal gastrectomy (LDG). In this study, we investigated the significance of prophylactic drain placement after LDG for gastric cancer. METHODS Seventy-eight consecutive patients with gastric cancer who underwent LDG in our department were retrospectively analyzed. The patients were divided into two groups according to the insertion of a prophylactic intra-abdominal drain following LDG. The 'drain group' comprised 45 patients with routine use of a prophylactic intra-abdominal drain, and the 'no-drain group' comprised 33 patients who did not undergo placement of an intra-abdominal drain. RESULTS There were no significant differences in terms of the mean age of the patients, male/female ratio, body mass index, and concurrent diseases between the drain group and the no-drain group. In addition, there were no significant differences in the tumor location, tumor diameter, depth of the tumor, nodal metastasis, and tumor stage between the two groups. All patients in each group were successfully treated with R0 surgery, and no patient required conversion to open surgery. Surgery-related factors, including lymph node dissection and operative time, were similar in the drain group and the no-drain group. A comparison of the amount of intraoperative blood loss between patients with and without postoperative complications revealed that patients who experienced postoperative complications had a significantly larger amount of blood loss than those without postoperative complications. A comparison of operative times between patients with and without surgery-related postoperative local complications revealed that patients who experienced surgery-related postoperative local complications had a significantly longer operative time than those without surgery-related postoperative local complications. Analysis of operative times in each group revealed that patients with surgery-related postoperative local complications had a significantly longer operative time than those without surgery-related postoperative local complications in the no-drain group. CONCLUSIONS Intraoperative factors such as the operative time and the amount of intraoperative blood loss affected the occurrence of postoperative complications following LDG. A prophylactic drain may thus be useful in patients at higher risk and in those with a longer operative time or massive intraoperative bleeding.", "qid": 34, "docid": "06uy54qy", "rank": 9, "score": 9.971599578857422}, {"content": "Title: Report of a series of healthy term newborns from convalescent mothers with COVID-19 Content: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable virus associated with a significantly increased risk of complications among the infected population. Few data are available for the outcome of pregnancy complicated by serious respiratory disease due to SARS-CoV-2 infection. AIM: We herein report a series of four neonates whose mothers had recovered from new coronavirus 2019 disease (COVID-19) diagnosed in the third trimester of pregnancy. METHODS: pregnant women with documented COVID-19 infection during their pregnancy, who gave birth in Parma Hospital, University of Parma, Italy, in March and April 2020, during the peak of incidence of COVID-19 in Italy. Clinical records and laboratory tests were retrospectively reviewed. RESULTS: All neonates were delivered at term in good conditions without congenital COVID-19 infection. CONCLUSIONS: Findings from our series of cases indicated that adverse effects on foetuses from pregnancies complicated by COVID-19 infection in late pregnancy are unlikely.", "qid": 34, "docid": "c87a4sf8", "rank": 10, "score": 9.892800331115723}, {"content": "Title: Report of a series of healthy term newborns from convalescent mothers with COVID-19. Content: BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable virus associated with a significantly increased risk of complications among the infected population. Few data are available for the outcome of pregnancy complicated by serious respiratory disease due to SARS-CoV-2 infection. AIM We herein report a series of four neonates whose mothers had recovered from new coronavirus 2019 disease (COVID-19) diagnosed in the third trimester of pregnancy. METHODS pregnant women with documented COVID-19 infection during their pregnancy, who gave birth in Parma Hospital, University of Parma, Italy, in March and April 2020, during the peak of incidence of COVID-19 in Italy. Clinical records and laboratory tests were retrospectively reviewed. RESULTS All neonates were delivered at term in good conditions without congenital COVID-19 infection. CONCLUSIONS Findings from our series of cases indicated that adverse effects on foetuses from pregnancies complicated by COVID-19 infection in late pregnancy are unlikely.", "qid": 34, "docid": "eanwxkvt", "rank": 11, "score": 9.892799377441406}, {"content": "Title: Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study Content: BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by &#967; test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a9.738, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a22.105, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a3.216, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a60.905, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and expectoration (32.1% vs. 12.1%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a13.250, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.625, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] \u00d710/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a7.618, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] \u00d710/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a8.037, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.315, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a5.242, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a2.592, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a7.308, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] \u00b5mol/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a6.478, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.206, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a1.219, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a148.105, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), acute cardiac injury (59.6% vs. 0.9%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a93.222, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), acute kidney injury (18.3% vs. 0%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a23.257, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), shock (11.9% vs. 0%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a14.618, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, &#967;\u00e2\u0080\u008a=\u00e2\u0080\u008a7.655, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.006). CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.", "qid": 34, "docid": "en413zlr", "rank": 12, "score": 9.887999534606934}, {"content": "Title: Characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan, China Content: Background Since Dec 2019, SARS-CoV-2 has caused about fifty thousand patients and over two thousand deaths in Wuhan, China. We reported characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, were retrospectively collected from electronic medical records. Characteristics were compared between patients who died or recovered, and between patients with different disease severity. Results By Feb 25, 2020, 403 patients were enrolled, 100 died and 303 recovered. Most of non-survivors tended to be males, old aged, or with chronic diseases. Duration from illness onset to admission was 9 (7-12) days. Patients with severe or critical illness had more days from onset to admission compared to those with ordinary illness. Lymphopenia, anemia, hypoproteinemia, and abnormal serum sodium were presented in 52.6%, 54.6%, 69.8%, and 21.8% cases, respectively. Patients who died or with severe/critical illness showed increased white blood cell and neutrophil count, serum total bilirubin, creatinine, hypersensitive troponin I, D-dimer, procalcitonin, and C-reactive protein, and decreased red blood cell, lymphocyte, platelet count, and serum albumin on admission compared to those who recovered or with ordinary illness. Complications of acute organ injury and secondary infection were common in patients with COVID-19, especially in non-survivors. Conclusions Multiple homeostasis disturbances were common in patients with severe or critical illness at admission. Early support should be provided, especially for old men with chronic disease, which is vital to control disease progression and reduce mortality of COVID-19 during epidemic ongoing outbreak.", "qid": 34, "docid": "x3c7zjvg", "rank": 13, "score": 9.806599617004395}, {"content": "Title: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Content: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question \"What rehabilitation services do survivors of COVID-19 require?\" The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "qid": 34, "docid": "7l17lern", "rank": 14, "score": 9.784500122070312}, {"content": "Title: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Content: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question \u201cWhat rehabilitation services do survivors of COVID-19 require?\u201d The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "qid": 34, "docid": "gfzobzrg", "rank": 15, "score": 9.784499168395996}, {"content": "Title: The impact of nutrition on COVID-19 susceptibility and long-term consequences Content: While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type 2 diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.", "qid": 34, "docid": "b999y89f", "rank": 16, "score": 9.741900444030762}, {"content": "Title: Supporting Adults Bereaved Through COVID-19: A Rapid Review of the Impact of Previous Pandemics on Grief and Bereavement Content: The global COVID-19 pandemic is likely to have a major impact on the experience of death, dying, and bereavement. This study aimed to review and synthesize learning from previous literature focused on the impact on grief and bereavement during other infectious disease outbreaks. We conducted a rapid scoping review according to the principles of the Joanna Briggs Institute and analyzed qualitative data using thematic synthesis. From the 218 identified articles, 6 were included in the analysis. They were four qualitative studies, one observational study, and a systematic review. Studies were conducted in West Africa, Haiti, and Singapore. No research studies have focused on outcomes and support for bereaved people during a pandemic. Studies have tended to focus on survivors who are those who had the illness and recovered, recognizing that some of these individuals will also be bereaved people. Previous pandemics appear to cause multiple losses both directly related to death itself and also in terms of disruption to social norms, rituals, and mourning practices. This affects the ability for an individual to connect with the deceased both before and after the death, potentially increasing the risk of complicated grief. In view of the limited research, specific learning from the current COVID-19 crisis and the impact on the bereaved would be pertinent. Current focus should include innovative ways to promote connection and adapt rituals while maintaining respect. Strong leadership and coordination between different bereavement organisations is essential to providing successful postbereavement support.", "qid": 34, "docid": "7tj94aue", "rank": 17, "score": 9.696399688720703}, {"content": "Title: The impact of nutrition on COVID-19 susceptibility and long-term consequences Content: Abstract While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type II diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.", "qid": 34, "docid": "0999t5x0", "rank": 18, "score": 9.657299995422363}, {"content": "Title: [SARS-CoV-2 infection (COVID-19): what can we expect?] Content: - Case numbers in China are clearly declining, case numbers in many European regions are no longer increasing exponentially.- Data on mortality from SARS-CoV-2 infection are contradictory; mortality is certainly lower than for SARS and MERS, but probably higher than for most seasonal flu outbreaks in recent years- The main complication of SARS-CoV-2 infection is pneumonia with development of acute respiratory distress syndrome (ARDS)- Asymptomatic and oligosymptomatic courses with virus shedding are not uncommon; they may be more frequent in children than in adults. Virus excretion in asymptomatic people and in the pre-symptomatic phase of an infection is relevant for transmission- An effective antiviral therapy has not yet been established. Steroids for anti-inflammatory therapy are not recommended- It is very important to prepare all actors in the health care system for a longer-term burden of inpatients and complications and to create the necessary capacities. Low-threshold diagnostic testing and rapid detection of infection chains remain essential for better control of the pandemic. An effective vaccine is urgent.", "qid": 34, "docid": "1242ggxm", "rank": 19, "score": 9.636899948120117}, {"content": "Title: Covid-19: accelerating recovery Content: Covid-19 infections and related illness and death are rightly at the forefront of our minds. It is critical that we consider how to reduce infections, treat those who are ill and protect health systems. We must, however, also consider how the pandemic is affecting the families of those infected, and how interventions to prevent the spread of the virus come with large negative economic and social consequences. We must begin to identify the ways in which we can soften these blows and recover from the negative consequences over the medium and long-term. We highlight here the importance of moving away the tendency to search for interventions to improve one outcome at a time. It will be essential, particularly in highly resource constrained settings, to look for accelerators, interventions which improve multiple outcomes simultaneously. We discuss how this will be especially important for groups who are at particular risk at this time, including of long-term negative outcomes. These include very young children, adolescents and those who have limited capacity to benefit from narrow interventions given critical needs in multiple domains. Searching for accelerators requires that we take a step back and look to identify common causes of negative outcomes and consider how we might address them. For many countries, recovery from this epidemic will be highly constrained by the limited availability of financial resources. Wise investments will be especially important at this time.", "qid": 34, "docid": "bhlp1acq", "rank": 20, "score": 9.59529972076416}, {"content": "Title: Predicting Illness Severity and Short-Term Outcomes of COVID-19: A Retrospective Cohort Study in China Content: Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4(+) lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age \u2265 55 years, BMI > 27 kg / m(2), IL-6 \u2265 20 pg / ml, CD4(+) T cell \u2264 400 count / \u03bc L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.", "qid": 34, "docid": "jkmtpin4", "rank": 21, "score": 9.471699714660645}, {"content": "Title: Clinical Features and Short-term Outcomes of 102 Patients with Corona Virus Disease 2019 in Wuhan, China Content: OBJECTIVE: In December, 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate clinical and laboratory features and short-term outcomes of patients with Corona Virus Disease 2019(COVID-19). METHODS: All patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between January 3 and February 1, 2020 were included. All those patients were with laboratory-confirmed infection. Epidemiological, clinical, radiological characteristics, underlying diseases, laboratory tests treatment, complications and outcomes data were collected. Outcomes were followed up at discharge until Feb 15, 2020. RESULTS: The study cohort included 102 adult patients. The median (IQR) age was 54 years (37-67years) and 48.0% were female. A total of 34 patients (33.3%) were exposed to source of transmission in the hospital setting (as health care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. Eighteen patients (17.6%) were admitted to the ICU, and 17 patients died (mortality, 16.7%; 95% confidence interval [CI], 9.4%-23.9%). Among patients who survived, they were younger, more likely were health care workers and less likely suffered from comorbidities. They were also less likely suffered from complications. There was no difference in drug treatment rates between the survival and non-survival groups. Patients who survived less likely required admission to the intensive care unit (14.1% vs. 35.3%). Chest imaging examination showed that death patients more likely had ground-glass opacity (41.2% vs. 12.9%). CONCLUSIONS: The mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. Patient characteristics seen more frequently in those who died were development of systemic complications following onset of the illness and the severity of disease requiring admission to the ICU. Our data support those described by others that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatment.", "qid": 34, "docid": "4i1djfn9", "rank": 22, "score": 9.46399974822998}, {"content": "Title: What is the best drug to treat COVID-19? The need for randomized controlled trials Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest public health challenge to the biomedical community of the last century Despite multiple public health measures, 1-3 there remains an urgent need for pharmacologic therapies to treat infected patients and minimize mortality, decrease pressures on intensive care units and health systems and optimally they should decrease subsequent transmission At the time of writing, there are no licensed drugs to treat COVID-19 and a search on clinicaltrials gov using \u2018COVID-19\u2019 as the input term, yielded 657 studies Drug-based interventions currently fall into categories including off label use which includes repurposed drugs, 4,5 and newer entities but both categories should be given in the context of clinical trials In Wuhan, China, then the epicentre of the pandemic, Cao et al under heroic circumstances, conducted a randomized, controlled, open-label trial involving 199 hospitalized patients with confirmed SARS-CoV-2 infection including as an entry criteria oxygen saturation (SaO2) of 94% or less on air (ChiCTR2000029308) Patients were randomly assigned 1:1 to receive either lopinavir\u2013ritonavir (400 mg and 100 mg, respectively) twice daily for 14 days, or standard care alone The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first 6 Even though their study showed no benefits with lopinavir\u2013ritonavir treatment beyond standard care, this is exactly the sort of study that best informs our treatment options Following this, we were surprised to see the New England Journal of Medicine publishing a single arm study on 61 patients who received at least one dose of remdesevir, again with similar entry criteria of SaO2 &lt;94% on air 7 Unlike the randomised trial by Cao et al , there was no accompanying editorial, but there was a subsequent an open letter discussing remdesevir studies from the CEO and Chairman of Gilead (https://www gilead com/stories/articles/an-open-letter-from-our-chairman-and-ceo) One presumes that the patients in the remdesevir single arm study, and several included in an earlier Lancet paper, 8 were recruited in perhaps easier conditions than those in Wuhan earlier this year Randomised trials are designed to precisely answer questions regarding toxicity and efficacy beyond standard of care and in the absence of an effective therapy it remains entirely reasonable and ethical at this point to perform a trial versus placebo They are much more informative than single arm studies which result in claims, perhaps borne from hope and/or desperation, that drugs work, 9 and such claims include those from physicians stating very high cure rates Clearly, recruiting patients recently diagnosed will have \u2018cure rates\u2019 usually in the high 90s%, unless one focuses on recruiting hospitalised patients and/or the elderly, frail, those with co-morbidities or a high body mass index, to name a few examples A well-known French microbiologist on social media has promoted the use of chloroquine to treat or prevent COVID-19 The FDA has approved it, although at the time of writing they haven\u2019t explained the rationale behind the approval, and as a consequence patients, institutions and the worried public have demanded immediate chloroquine for all The resulting rush on chloroquine has led to severe shortages of the drug, and patients taking regular chloroquine or hydroxychloroquine for lupus or other systemic diseases had to stop their treatment due to a lack of supply This drug has well known often serious toxicities;10 we note one small study was stopped due to potential cardiac complications (https://www nytimes com/2020/04/12/health/chloroquine-coronavirus-trump html) and we suggest it should only be taken in the context of a randomised or other clinical study This is not to suggest single arm studies are not helpful: they inform subsequent trials includi g dosage, duration and appropriate endpoints For example, we have observed11 that use of baricitinib for 10 days is associated with viral rebound in nasopharyngeal swabs in rapidly recovered and discharged patients, and thus have recommended longer use in the large randomised studies in which it is included, and we suggest again that comparisons between different therapies or placebo are likely to yield more informative results than randomised studies comparing 10 days of intravenous remdesevir with 5 days (https://benevolent ai/news/potential-treatment-for-covid-19-identified-by-benevolentai-usingartificial-intelligence-enters-clinical-testing And https://investor lilly com/news-releases/news-release-details/lilly-begins-clinical-testingtherapies-covid-19) With this in mind, we thoroughly congratulate the authors from Guangzhou, China, who successfully randomised 86 individuals with mild-to-moderate COVID-19 in a 2:2:1 design, to either lopinavir/ritonavir, arbidol (a broad spectrum viral infusion inhibitor12) or placebo (NCT04252885) Because they included only mild-to-moderate patients, the pre-defined primary endpoint was the conversion at day 21 of positive-to-negative PCR tests for SARSCoV-2 from nasopharyngeal swabs The real time reverse-transcriptase PCR (RT-PCR) method used was indeed appropriate as it was performed simultaneously on two target genes, ORF1ab and N genes, and positive and negative controls were used at each batch Negative conversion required 2 separate real time RT-PCR tests separated by 24 hours, and the entry criteria for the definition of mild-to-moderate including the absence of pneumonia are entirely appropriate Baseline criteria between the 3 groups were well-matched (a criticism of one of the hydroxychloroquine randomised studies is this was not the case13) and follow up was appropriate Their data helpfully shows there was no difference between any of the groups in the primary endpoint In the continuing search for safe and effective new therapies to treat patients with COVID-19, we require well-conducted ethical studies including prospective, randomised, placebocontrolled clinical studies such as this Although many drugs have predicted in vitro activity against the virus, the proposal that such drugs might provide more benefit than harm is not appropriate with no evidence base supporting efficacy in any patients infected with SARSCoV-2 A preprint reporting results from a randomised trial of the anti-viral favipravir versus arbidol in 240 adults has shown no difference in clinical recovery at 7 days, but cough and pyrexia were improved on favipravir 14 These authors and Li et al should be applauded for their efforts to add a useful randomised trial to the literature, albeit one that is negative It is critical to publish such studies International multicentre trials, such as Discovery (NCT04315948) and Solidarity (EudraCT Number 2020-000982-18), will randomise patients with COVID-19 to receive different drugs in adaptive study designs Such initiatives will provide the best and most relevant data to guide management of patients with COVID-19 Whether antiviral, immunomodulatory or antimalarial drugs could be effective in changing the disease course in patients with either mild or severe COVID-19 remains unknown When patients take these off-label and recover it is not known whether the drug was helpful in the disease course without randomisation Similarly, when patients deteriorate, we do not know if they should be continued or considered clinically ineffective and stopped Assessing viral loads by PCR on nasopharyngeal swabs as performed in the trial here, will help clarify the roles of these medicines going forwards", "qid": 34, "docid": "tvs1snq8", "rank": 23, "score": 9.320599555969238}, {"content": "Title: To recover faster from Covid-19, open up: Managerial implications from an open innovation perspective Content: Abstract Covid-19 has severely tested our public health systems. Recovering from Covid-19 will soon test our economic systems. Innovation will have an important role to play in recovering from the aftermath of the coronavirus. This article discusses both how to manage innovation as part of that recovery, and also derives some lessons from how we have responded to the virus so far, and what those lessons imply for managing innovation during the recovery.", "qid": 34, "docid": "gd5btv69", "rank": 24, "score": 9.318400382995605}, {"content": "Title: Supporting adults bereaved through COVID-19: a rapid review of the impact of previous pandemics on grief and bereavement Content: The global COVID-19 pandemic is likely to have a major impact on the experience of death, dying and bereavement. This study aimed to review and synthesise learning from previous literature focused on the impact on grief and bereavement during other infectious disease outbreaks. We conducted a rapid scoping review according to the principles of the Joanna Briggs Institute and analysed qualitative data using thematic synthesis. From the 218 identified papers, 6 were included in the analysis. They were four qualitative studies, one observational study and a systematic review. Studies were conducted in West Africa, Haiti and Singapore. No research studies have focused on outcomes and support for bereaved people during a pandemic. Studies have tended to focus on survivors i.e. those who had the illness and recovered, recognising that some of these individuals will also be bereaved people. Previous pandemics appear to cause multiple losses both directly related to death itself but also in terms of disruption to social norms, rituals and mourning practices. This affects the ability for an individual to connect with the deceased both before and after the death, potentially increasing the risk of complicated grief. In view of the limited research, specific learning from the current COVID-19 crisis and the impact on the bereaved would be pertinent. Current focus should include innovative ways to promote connection and adapt rituals while maintaining respect. Strong leadership and coordination between different bereavement organisations is essential to providing successful post-bereavement support.", "qid": 34, "docid": "bad72hhm", "rank": 25, "score": 9.314900398254395}, {"content": "Title: Coronavirus disease 2019 (COVID-19) pneumonia in a hemodialysis patient: A case report Content: RATIONALE: The 2019 novel coronavirus disease (COVID-19) causes a novel, atypical pneumonia that has brought huge public health challenges across the globe. There is limited data about patients with end-stage renal disease who also suffer from COVID-19. In this report, we discuss the case of a hemodialysis patient who developed COVID-19 pneumonia in the clinical course. PATIENT CONCERNS: A 79-year-old man who had end-stage renal disease (ESRD) and was taking regular hemodialysis was admitted to hospital for a fever and dry cough. The patient, who also had cardiovascular disease, had no history of contact with COVID-2019 patients. DIAGNOSIS: The patient was diagnosed with COVID-2019 by the reverse-transcriptase polymerase chain reaction (RT-PCR), and his pharyngeal swab for SARS-CoV-2 was positive. INTERVENTION: The treatment was mainly supportive and the patient was intensively monitored. He was treated with oxygen, broad-spectrum antibiotics, antiviral drugs, and methylprednisolone. The patient took continuous renal replacement therapy (CRRT) every 2 days. OUTCOMES: After 19 days, an RT-PCR assay for SARS-CoV-2 was negative, and computed tomography (CT) of the patient's thorax indicated that the pulmonary inflammatory exudation was absorbed and pulmonary infection improved significantly. He was discharged on day 29 after recovering from COVID-2019 pneumonia. LESSONS: The courses of disease and treatment options for this individual were significantly more complicated than those for ordinary patients. Therefore, it was necessary to monitor the condition of the patient closely and to protect the dialysis unit staff from being infected. Compared with other severe COVID-2019 cases, this patient recovered more quickly following treatment, which was likely due to the removal of inflammatory mediators by CRRT. This implies that blood purification might be an important option for hemodialysis patients with COVID-19.", "qid": 34, "docid": "cnzbxg1i", "rank": 26, "score": 9.246899604797363}, {"content": "Title: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome Content: This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.", "qid": 34, "docid": "ppod1igx", "rank": 27, "score": 9.194499969482422}, {"content": "Title: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome. Content: This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.", "qid": 34, "docid": "svgknqud", "rank": 28, "score": 9.194499015808105}, {"content": "Title: Laparoscopic common bile duct exploration in patients with complicated cholecystitis: a safety and feasibility study. Content: BACKGROUND Laparoscopic cholecystectomy (LC) with common bile duct exploration (LCBDE) is nowadays a preferred one-stage treatment. However, the influence of complicated cholecystitis (CC) on LCBDE has rarely been addressed. In the present study we aimed to verify whether severe gallbladder inflammation would adversely affect the outcome of LCBDE. MATERIAL AND METHODS From 2008 to 2011, all patients undergoing LC and LCBDE at China Medical University Hospital were included. Patients were divided into two groups based on the severity of cholecystitis. Those with unstable hemodynamics and co-morbidities who were deemed unfit for general anesthesia were excluded. Patient demographics, surgical results, and outcome were compared between the groups. RESULTS During the study period, 117 patients diagnosed with cholecystitis were found to have common bile duct (CBD) stones and underwent LC + LCBDE. Of these 117 patients, 87 had uncomplicated cholecystitis (UC) and the remaining 30 patients had CC. There was no demographic difference between the groups, but for patients with CC there were marginally longer operative times (190 vs. 223 min, p = 0.141), more blood loss (10 vs. 150 ml, p < 0.05), and longer postoperative hospital stays (6 vs. 7 days, p < 0.05). The risk of developing major intraoperative complications was not greater for those with CC. Conversion to open cholecystectomy was necessary in a total of 12 cases (10 %) with an overall 1 % mortality rate. CONCLUSIONS Complicated cholecystitis was not a contraindication for LCBDE. Complete stone clearance can be achieved in a substantial number of cases with an acceptable complication rate. Further prospective randomized studies are required to validate its long-term safety.", "qid": 34, "docid": "j4dybie1", "rank": 29, "score": 9.193599700927734}, {"content": "Title: Predictive Data Mining Models for Novel Coronavirus (COVID-19) Infected Patients\u2019 Recovery Content: Novel coronavirus (COVID-19 or 2019-nCoV) pandemic has neither clinically proven vaccine nor drugs; however, its patients are recovering with the aid of antibiotic medications, anti-viral drugs, and chloroquine as well as vitamin C supplementation. It is now evident that the world needs a speedy and quicker solution to contain and tackle the further spread of COVID-19 across the world with the aid of non-clinical approaches such as data mining approaches, augmented intelligence and other artificial intelligence techniques so as to mitigate the huge burden on the healthcare system while providing the best possible means for patients' diagnosis and prognosis of the 2019-nCoV pandemic effectively. In this study, data mining models were developed for the prediction of COVID-19 infected patients\u2019 recovery using epidemiological dataset of COVID-19 patients of South Korea. The decision tree, support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor algorithms were applied directly on the dataset using python programming language to develop the models. The model predicted a minimum and maximum number of days for COVID-19 patients to recover from the virus, the age group of patients who are of high risk not to recover from the COVID-19 pandemic, those who are likely to recover and those who might be likely to recover quickly from COVID-19 pandemic. The results of the present study have shown that the model developed with decision tree data mining algorithm is more efficient to predict the possibility of recovery of the infected patients from COVID-19 pandemic with the overall accuracy of 99.85% which stands to be the best model developed among the models developed with other algorithms including support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor.", "qid": 34, "docid": "dvg0isgt", "rank": 30, "score": 9.129300117492676}, {"content": "Title: Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients Content: OBJECTIVES: To compare clinical, laboratory, and chest computed tomography (CT) findings in critically ill patients diagnosed with coronavirus disease 2019 (COVID-19) who survived and who died. METHODS: This retrospective study reviewed 60 critically ill patients (43 males and 17 females, mean age 64.4 \u00b1 11.0 years) with COVID-19 pneumonia who were admitted to two different clinical centers. Their clinical and medical records were analyzed, and the chest CT images were assessed to determine the involvement of lobes and the distribution of lesions in the lungs between the patients who recovered from the illness and those who died. RESULTS: Compared with recovered patients (50/60, 83%), deceased patients (10/60, 17%) were older (mean age, 70.6 vs. 62.6 years, p = 0.044). C-reactive protein (CRP) (110.8 \u00b1 26.3 mg/L vs 63.0 \u00b1 50.4 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR) (18.7 \u00b1 16.6 vs 8.4 \u00b1 7.5, p = 0.030) were significantly elevated in the deceased as opposed to the recovered. Medial or parahilar area involvement was observed in all the deceased patients (10/10, 100%), when compared to only 54% (27/50) in the recovered. Ground-glass opacities (97%), crazy-paving pattern (92%), and air bronchogram (93%) were the most common radiological findings. There was significant difference in diabetes (p = 0.025) and emphysema (p = 0.013), and the odds ratio on a deceased patient having diabetes and emphysema was 6 times and 21 times the odds ratio on a recovered patient having diabetes and emphysema, respectively. CONCLUSIONS: Older patients with comorbidities such as diabetes and emphysema, and higher CRP and NLRs with diffuse lung involvement were more likely to die of COVID-19. KEY POINTS: \u00e2\u0080\u00a2 Almost all patients critically ill with COVID-19 pneumonia had five lung lobes involved. \u00e2\u0080\u00a2 Medial or parahilar area involvement and degree of lung involvement were more serious in the deceased patients when compared with those who recovered from treatment. \u00e2\u0080\u00a2 Chronic lung disease, e.g., emphysema, diabetes, and higher serum CRP and NLR characterized patients who died of COVID-19.", "qid": 34, "docid": "5zhmn92u", "rank": 31, "score": 9.093700408935547}, {"content": "Title: Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients Content: OBJECTIVES: To compare clinical, laboratory, and chest computed tomography (CT) findings in critically ill patients diagnosed with coronavirus disease 2019 (COVID-19) who survived and who died. METHODS: This retrospective study reviewed 60 critically ill patients (43 males and 17 females, mean age 64.4 \u00b1 11.0 years) with COVID-19 pneumonia who were admitted to two different clinical centers. Their clinical and medical records were analyzed, and the chest CT images were assessed to determine the involvement of lobes and the distribution of lesions in the lungs between the patients who recovered from the illness and those who died. RESULTS: Compared with recovered patients (50/60, 83%), deceased patients (10/60, 17%) were older (mean age, 70.6 vs. 62.6 years, p = 0.044). C-reactive protein (CRP) (110.8 \u00b1 26.3 mg/L vs 63.0 \u00b1 50.4 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR) (18.7 \u00b1 16.6 vs 8.4 \u00b1 7.5, p = 0.030) were significantly elevated in the deceased as opposed to the recovered. Medial or parahilar area involvement was observed in all the deceased patients (10/10, 100%), when compared to only 54% (27/50) in the recovered. Ground-glass opacities (97%), crazy-paving pattern (92%), and air bronchogram (93%) were the most common radiological findings. There was significant difference in diabetes (p = 0.025) and emphysema (p = 0.013), and the odds ratio on a deceased patient having diabetes and emphysema was 6 times and 21 times the odds ratio on a recovered patient having diabetes and emphysema, respectively. CONCLUSIONS: Older patients with comorbidities such as diabetes and emphysema, and higher CRP and NLRs with diffuse lung involvement were more likely to die of COVID-19. KEY POINTS: \u2022 Almost all patients critically ill with COVID-19 pneumonia had five lung lobes involved. \u2022 Medial or parahilar area involvement and degree of lung involvement were more serious in the deceased patients when compared with those who recovered from treatment. \u2022 Chronic lung disease, e.g., emphysema, diabetes, and higher serum CRP and NLR characterized patients who died of COVID-19.", "qid": 34, "docid": "wnd0ewz1", "rank": 32, "score": 9.09369945526123}, {"content": "Title: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Content: BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients\u2019 oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0\u201362.0) years were analyzed. After in-hospital treatment, patients\u2019 inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0\u201311.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients\u2019 stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0\u201316.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0\u20134.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients\u2019 urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R(2) = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients\u2019 stools (t = \u22122.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients\u2019 stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.", "qid": 34, "docid": "3i8k3bo5", "rank": 33, "score": 9.084799766540527}, {"content": "Title: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19() Content: INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory disfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1(st), 2020. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p = 0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p = 0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p = 0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p = 0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.", "qid": 34, "docid": "s1mym0kq", "rank": 34, "score": 9.053600311279297}, {"content": "Title: Short-Term Outcomes of Laparoscopic Total Gastrectomy Performed by a Single Surgeon Experienced in Open Gastrectomy: Review of Initial Experience. Content: PURPOSE Laparoscopic total gastrectomy (LTG) is more complicated than laparoscopic distal gastrectomy, especially during a surgeon's initial experience with the technique. In this study, we evaluated the short-term outcomes of and learning curve for LTG during the initial cases of a single surgeon compared with those of open total gastrectomy (OTG). MATERIALS AND METHODS Between 2009 and 2013, 134 OTG and 74 LTG procedures were performed by a single surgeon who was experienced with OTG but new to performing LTG. Clinical characteristics, operative parameters, and short-term postoperative outcomes were compared between groups. RESULTS Advanced gastric cancer and D2 lymph node dissection were more common in the OTG than LTG group. Although the operation time was significantly longer for LTG than for OTG (175.7\u00b143.1 minutes vs. 217.5\u00b163.4 minutes), LTG seems to be slightly superior or similar to OTG in terms of postoperative recovery measures. The operation time moving average of 15 cases in the LTG group decreased gradually, and the curve flattened at 54 cases. The postoperative complication rate was similar for the two groups (11.9% vs. 13.5%). No anastomotic or stump leaks occurred. CONCLUSIONS Although LTG is technically difficult and operation time is longer for surgeons experienced in open surgery, it can be performed safely, even during a surgeon's early experience with the technique. Considering the benefits of minimally invasive surgery, LTG is recommended for early gastric cancer.", "qid": 34, "docid": "0ys6hqn7", "rank": 35, "score": 8.982099533081055}, {"content": "Title: Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Content: OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.", "qid": 34, "docid": "hia1me9i", "rank": 36, "score": 8.976499557495117}, {"content": "Title: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19 Content: INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory dysfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1st, 2020. Participants were posteriorly asked by e-mail to verify data on the recovery of sudden olfactory loss and test for COVID-19 at the end of the data collection period. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p=0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p=0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p=0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p=0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.", "qid": 34, "docid": "diui92j4", "rank": 37, "score": 8.936300277709961}, {"content": "Title: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Content: BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F\u00e2\u0080\u008a=\u00e2\u0080\u008a2.669, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.044, and adjusted R\u00e2\u0080\u008a=\u00e2\u0080\u008a0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t\u00e2\u0080\u008a=\u00e2\u0080\u008a-2.699, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t\u00e2\u0080\u008a=\u00e2\u0080\u008a2.550, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t\u00e2\u0080\u008a=\u00e2\u0080\u008a4.631, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P\u00e2\u0080\u008a>\u00e2\u0080\u008a0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.", "qid": 34, "docid": "dtmux7iq", "rank": 38, "score": 8.888500213623047}, {"content": "Title: Needs of individuals recovering from a first episode of mental illness: A scoping review. Content: Central to the role of mental health clinicians is the assessment of needs. A number of assessment tools have been used to evaluate the needs of individuals diagnosed with a mental illness. These tools have largely been developed for people with a severe and persistent mental illness and may not be suitable for individuals who are recovering from a first episode of mental illness. The aims of this review were therefore to identify the needs experienced by individuals recovering from a first episode of mental illness; determine what tools have been used to evaluate these needs; and explore whether existing tools adequately reflect the needs described in the literature. Twenty-one articles were included, comprising articles which identified needs (n = 10), needs assessment tools (n = 1), or articles which identified both needs and a needs assessment tool (n = 10). Results indicate that individuals who have been admitted to a specialized mental health unit and are recovering from a first episode of mental illness may experience an extensive range of needs, spanning emotional, psychological, social, informational, functional, practical, and relationship needs. Four established needs assessment tools were found to have been used to evaluate these needs; however, these do not appear to represent all needs discovered in this review, were mostly developed for populations with a long-term mental illness, and may not be suitable for assessing the needs of individuals recovering from a first episode of mental illness following a presentation to a specialized mental health unit.", "qid": 34, "docid": "9dfg295j", "rank": 39, "score": 8.776300430297852}, {"content": "Title: Endoscopic Thyroidectomy Using the Unilateral Axillo-breast Approach Versus the Modified Anterior Chest Wall Approach: A Prospective Comparative Study. Content: INTRODUCTION Endoscopic thyroidectomy (ET) has become a well-established surgical technique that is mainly performed for benign thyroid lesions. Several endoscopic approaches are available, such as transaxillary, unilateral axillo-breast approach (UABA), modified anterior chest wall approach (MACWA), bilateral axillo-breast approach, and most recently the transoral approach and the robotic-assisted techniques. There is no recommended approach, because each approach has its own positive and negative attributes. We, herein, compare between UABA and MACWA in terms of surgical and cosmetic outcomes. METHODS This prospective study was conducted from April 2016 to August 2017. Forty patients with unilateral benign thyroid lesions were selected. Of them, 20 patients underwent ET using UABA, and 20 patients underwent ET using MACWA. Gas insufflation was implemented for all patients. Clinicopathologic data, surgical outcomes, and cosmetic outcomes in both groups were analyzed. RESULTS There was no significant difference between both groups in the clinicopathologic characteristics. The mean surgical time was significantly longer in the UABA group compared with the chest wall group (147.3 vs. 124.3 min). The postoperative pain scores were relatively lower in the UABA group compared with the MACWA group. We reported a higher rate of persistent paresthesia, neck contracture with swallowing discomfort, and hypertrophic scars in the MACWA group. Cosmetic satisfaction scores for patients who underwent UABA were higher than for those who underwent MACWA. CONCLUSIONS Both approaches were similar in terms of safety, feasibility, and operative complications. Even though the surgical time was longer, patients who underwent the UABA reported relatively less postoperative pain, superior cosmetic results, scar perception, and patient satisfaction compared with MACWA.", "qid": 34, "docid": "2062233b", "rank": 40, "score": 8.715800285339355}, {"content": "Title: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Content: Background: A patient&rsquo;s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively The reverse transcription polymerase chain reaction (RT-PCR) results for patients&rsquo;oropharyngeal swab, stool, urine, and serum samples were collected and analyzed Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study In total, 28 (42 4%) women and 38 men (57 6%) with a median age of 44 0 (34 0&ndash;62 0) years were analyzed After in-hospital treatment, patients&rsquo;inflammatory indicators decreased with improved clinical condition The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9 5 (6 0&ndash;11 0) days By February 10, 2020, 11 convalescent patients (16 7%) still tested positive for viral RNA from stool specimens and the other 55 patients&rsquo;stool specimens were negative for 2019-nCoV following a median duration of 11 0 (9 0&ndash;16 0) days after symptom onset Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2 0 (1 0&ndash;4 0) days Results for only four (6 9%) urine samples were positive for viral nucleic acid out of 58 cases;viral RNA was still present in three patients&rsquo;urine specimens after throat swabs were negative Using a multiple linear regression model ( F =2 669, P =0 044, and adjusted R 2 =0 122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients&rsquo;stools ( t =-2 699, P =0 010) The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8 0 days, respectively;t =2 550, P =0 013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively;t =4 631, P &lt;0 001) There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results ( P &gt;0 05) Conclusions: In brief, as the clearance of viral RNA in patients&rsquo;stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease The duration of RNA detection may relate to host cell immunity", "qid": 34, "docid": "bcl5776f", "rank": 41, "score": 8.701000213623047}, {"content": "Title: High prevalence of disordered eating behavior in Danish children and adolescents with type 1 diabetes Content: OBJECTIVE: A higher prevalence of disordered eating behavior (DEB) has been demonstrated in children and adolescents with type 1 diabetes (T1D) compared to healthy aged-matched peers. DEB is associated with higher HbA1c levels and increased risk of developing complications to T1D. The aim of this study was to determine the prevalence of DEB in a Danish cohort of children and adolescents with T1D aged 11-19 years and to characterize them regarding metabolic control and relevant clinical data. RESEARCH DESIGN & METHODS: In a cross-sectional study, we determined the prevalence of DEB using the revised Diabetes Eating Problem Survey (DEPS-R) questionnaire. HbA1c and relevant clinical data were obtained at the time they filled in the questionnaire. RESULTS: 192 children and adolescents (46% girls) aged 11-19 years with T1D were included from the pediatric diabetes outpatient clinic. A total of 40 participants (21%) had DEB. The prevalence was higher amongst girls compared with boys (34.1% vs 8.9%) and those who had DEB were older (16.7 vs 15.0 years, P < 0.001), had longer duration of T1D (7.5 vs 4.9 years, P < 0.001), higher BMI Z-scores (1.2 vs 0.3, P < 0.001), higher HbA1c (72.8 (8.8%) vs 62.0 (7.8%) mmol/mol, P < 0.001), higher total cholesterol (4.6 mmoL/L vs 4.2 mmoL/L, P = 0.0048) and LDL (2.7 vs 2.3, P = 0.001) compared with those with no signs of DEB. CONCLUSION: As in other countries, the prevalence of DEB is high in Danish adolescents with T1D. Early detection of DEB is essential to prevent short- and long-term complications to T1D. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "8st4kg8g", "rank": 42, "score": 8.690099716186523}, {"content": "Title: High prevalence of disordered eating behavior in Danish children and adolescents with type 1 diabetes. Content: OBJECTIVE A higher prevalence of disordered eating behavior (DEB) has been demonstrated in children and adolescents with type 1 diabetes (T1D) compared to healthy aged-matched peers. DEB is associated with higher HbA1c levels and increased risk of developing complications to T1D. The aim of this study was to determine the prevalence of DEB in a Danish cohort of children and adolescents with T1D aged 11-19 years and to characterize them regarding metabolic control and relevant clinical data. RESEARCH DESIGN & METHODS In a cross-sectional study, we determined the prevalence of DEB using the revised Diabetes Eating Problem Survey (DEPS-R) questionnaire. HbA1c and relevant clinical data were obtained at the time they filled in the questionnaire. RESULTS 192 children and adolescents (46% girls) aged 11-19 years with T1D were included from the pediatric diabetes outpatient clinic. A total of 40 participants (21%) had DEB. The prevalence was higher amongst girls compared with boys (34.1% vs 8.9%) and those who had DEB were older (16.7 vs 15.0 years, P < 0.001), had longer duration of T1D (7.5 vs 4.9 years, P < 0.001), higher BMI Z-scores (1.2 vs 0.3, P < 0.001), higher HbA1c (72.8 (8.8%) vs 62.0 (7.8%) mmol/mol, P < 0.001), higher total cholesterol (4.6 mmoL/L vs 4.2 mmoL/L, P = 0.0048) and LDL (2.7 vs 2.3, P = 0.001) compared with those with no signs of DEB. CONCLUSION As in other countries, the prevalence of DEB is high in Danish adolescents with T1D. Early detection of DEB is essential to prevent short- and long-term complications to T1D. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "sx1zgb2d", "rank": 43, "score": 8.690098762512207}, {"content": "Title: Evaluation of patients undergoing abdominal sacrocolpopexy due to symptomatic pelvic organ prolapse in terms of gastrointestinal complications. Content: Objectives To evaluate the intra- and postoperative gastrointestinal complications following abdominal sacrocolpopexy and determine the possible causes. Methods A total of 86 patients who underwent abdominal sacrocolpopexy due to symptomatic pelvic organ prolapse between January 2014 and January 2016 at \u0130zmir Tepecik Training and Research Hospital Obstetrics and Gynecology Clinic were retrospectively reviewed using the hospital information system. Patients were divided into two groups: those with and without prolonged length of hospital stay. They were evaluated in terms of gastrointestinal complications and risk factors. Results The reason for prolonged hospitalization was nausea and vomiting in 24 (88%) of 27 patients. The symptoms in these patients were recovered with hydration, stopping of oral intake, and administration of antiemetics. Nasogastric decompression and parenteral nutrition were required in three (11%) patients due to clinical and radiological evidence of ileus. The parameter that significantly prolonged the length of hospital stay was prior abdominal surgery (p < 0.05). Conclusion There were obvious gastrointestinal complications in three out of 27 patients with prolonged length of hospital stay. These findings may be beneficial for preoperative patient counselling.", "qid": 34, "docid": "1m8pn9e7", "rank": 44, "score": 8.664799690246582}, {"content": "Title: Taking the Longer View of COVID\u201019 Content: What are the prospects for dealing with COVID\u201019 more effectively in the future? This editorial addresses the question from the perspective of long\u2010term control of coronavirus infection.", "qid": 34, "docid": "hu9oxea1", "rank": 45, "score": 8.648699760437012}, {"content": "Title: Medium-Term Results of Laparoscopic Sleeve Gastrectomy: a Matched Comparison with Gastric Bypass. Content: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is considered a primary bariatric surgery and is increasingly being performed worldwide; however, long-term data regarding the durability of this procedure are inadequate. Here, we report the long-term results of LSGs in comparison to those of gastric bypass surgeries. METHODS A prospectively collected bariatric database from Ming-Shen General Hospital was retrospectively studied. Five hundred nineteen morbidly obese patients (mean age 36.0 \u00b1 9.1 years old (14-71), 74.6 % female, mean body mass index (BMI) 37.5 \u00b1 6.1 kg/m(2)) underwent LSG as a primary bariatric procedure from 2006 to 2012 at our institute. The operative parameters, weight loss, laboratory data, and quality of life were followed. Another two matched groups of laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic single anastomosis (mini-) gastric bypass (SAGB) patients who were matched in terms of age, sex, and BMI were recruited for comparisons. RESULTS The mean surgical time for LSG was 113.5 \u00b1 31.3 min, and the mean blood loss was 49.1 + 100.9 ml. The rate of major complications was 1.6 %, and the average length of the postoperative stay was 3.0 \u00b1 1.7 days. The operation times of the RYGB patients were longer than those of both the LSG and SAGB patients. The RYGB and SAGB patients experienced higher major complication rate than the LSG patients. The weight loss of the LSG patient at 5 years was 28.3 + 8.9 %, and the mean BMI was 27.1 + 4.3. The RYGB patients exhibited a 5-year weight loss similar to the LSG patients, and the SAGB patients exhibited greater weight loss than both of the other groups. Both the RYGB and SAGB patients exhibited significantly better glycemic control and lower blood lipids than the LSG patients, but the LSG patients exhibited a lesser micronutrient deficiency than the RYGB and SAGB groups. All three of the groups exhibited improved quality of life at 5 years after surgery, and there was no significant between-group difference in this measure. CONCLUSIONS LSG appears to be an ideal bariatric surgery, and the efficacy of this surgery is not inferior to that of gastric bypass.", "qid": 34, "docid": "oz6lmaj8", "rank": 46, "score": 8.607999801635742}, {"content": "Title: Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression Content: The current outbreak of Coronavirus Disease 2019 (COVID-19) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID-19 pneumonia. This is a 52-year-old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non-transplanted COVID-19 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone-based therapy, the COVID-19 pneumonia in this long-term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID-19 pneumonia.", "qid": 34, "docid": "cwmw3ru9", "rank": 47, "score": 8.598199844360352}, {"content": "Title: Successful recovery of COVID\u201019 pneumonia in a renal transplant recipient with long\u2010term immunosuppression Content: The current outbreak of Coronavirus Disease 2019 (COVID\u201019) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID\u201019 pneumonia. This is a 52\u2010year\u2010old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non\u2010transplanted COVID\u201019 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone\u2010based therapy, the COVID\u201019 pneumonia in this long\u2010term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID\u201019 pneumonia.", "qid": 34, "docid": "t2np6qa5", "rank": 48, "score": 8.598198890686035}, {"content": "Title: Long-term third-party assessment of results after continent cutaneous diversion with Lundiana pouch. Content: OBJECTIVES To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch. PATIENTS AND METHODS Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent review of the patient files. RESULTS A complication of Clavien-Dindo grade \u2265III, including unscheduled re-admissions, occurred in 45/193 patients (23%) at \u226490 days of surgery. At a median follow-up of 13 years, 105/193 patients (54%) had undergone at least one re-operation, with uretero-intestinal stricture being the most prevalent cause [28 patients (15%)]. Re-operations were more prevalent in patients operated during the first half of the study period than during the second half (2000-2007; 62% vs 47%; P = 0.03), and they were also more frequent in patients who underwent surgery for benign causes than in patients who underwent surgery for malignancy (60% vs 51%; P = 0.04). Continence was achieved in 172/188 patients (91%). In all, 16% of all patients required revisional surgery of the outlet to remain continent with an easily catheterisable pouch or to address stomal stenosis. The mean decrease in estimated glomerular filtration rate was more pronounced in patients with benign indications for urinary diversion than in those with malignancies, even after adjusting for younger age at surgery and longer follow-up in the former group (22 vs 11 mL/min/1.73 m2 ; P < 0.006). A disinterested third-party assessment revealed 10 postoperative complications, 17 re-operations during follow-up, and seven occasions of hospitalisation due to pyelonephritis (included in data above) not recorded at the primary data review. CONCLUSIONS The Lundiana pouch is associated with a high risk of re-operation, although the functional results are good. Independent review by a third party increased the validity of the outcome data.", "qid": 34, "docid": "d4rhaogf", "rank": 49, "score": 8.551400184631348}, {"content": "Title: Robotic assisted gastrectomy compared with open resection: a case-matched study. Content: In recent years, increasingly sophisticated tools have allowed for more complex robotic surgery. Robotic gastrectomy, however, is adopted in only a few selected centers. The goals of this study were to examine the adoption of robotic gastrectomy and to compare outcomes between open and robotic gastric resections. This is a case-matched analysis of patients who underwent robotic and open gastric resection performed at Sanchinarro University Hospital, Madrid from November 2011 to February 2017. Patient data were obtained retrospectively. Clinicopathologic characteristics and perioperative and postoperative outcomes were recorded and analyzed. Two groups of demographically similar patients were analyzed: the robotic group (n = 20) and the open surgery group (n = 19). The patient characteristics of the two groups have been compared. Robotic resection resulted in less blood loss, shorter postoperative hospital stay, and a longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Robotic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes are comparable to those patients who underwent open resection. Robotic gastrectomy resulted in a shorter hospital stay, less blood loss and morbidity comparable with the outcomes of open gastrectomy.", "qid": 34, "docid": "v0v91qov", "rank": 50, "score": 8.544099807739258}, {"content": "Title: Cross-sectional IgM and IgG profiles in SARS-CoV-2 infection Content: BACKGROUND: Accurate serological assays can improve the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but few studies have compared performance characteristics between assays in symptomatic and recovered patients. METHODS: We recruited 32 patients who had 2019 coronavirus disease (COVID-19; 18 hospitalized and actively symptomatic, 14 recovered mild cases), and measured levels of IgM (against the full-length S1 or the highly homologous SARS-CoV E protein) and IgG (against S1 receptor binding domain [RBD]). We performed the same analysis in 103 pre-2020 healthy adult control (HC) participants and 13 participants who had negative molecular testing for SARS-CoV-2. RESULTS: Anti-S1-RBD IgG levels were very elevated within days of symptom onset for hospitalized patients (median 2.04 optical density [OD], vs. 0.12 in HC). People who recovered from milder COVID-19 only reached similar IgG levels 28 days after symptom onset. IgM levels were elevated early in both groups (median 1.91 and 2.12 vs. 1.14 OD in HC for anti-S1 IgM, 2.23 and 2.26 vs 1.52 in HC for anti-E IgM), with downward trends in hospitalized cases having longer disease duration. The combination of the two IgM levels showed similar sensitivity for COVID-19 as IgG but greater specificity, and identified 4/10 people (vs. 3/10 by IgG) with prior symptoms and negative molecular testing to have had COVID-19. CONCLUSIONS: Disease severity and timing both influence levels of IgM and IgG against SARS-CoV-2, with IgG better for early detection of severe cases but IgM more suited for early detection of milder cases.", "qid": 34, "docid": "m2jal43g", "rank": 51, "score": 8.506799697875977}, {"content": "Title: Long-Term Survival after Radiofrequency Ablation of Lung Oligometastases from Five Types of Primary Lesions: A Retrospective Evaluation. Content: PURPOSE To conduct a retrospective evaluation of long-term survival after radiofrequency (RF) ablation for lung oligometastases from 5 types of primary lesions. MATERIALS AND METHODS The study population consisted of 123 patients with lung oligometastases from colorectal cancer (CRC), non-small-cell lung cancer, hepatocellular carcinoma, esophageal cancer, and renal-cell carcinoma treated with RF ablation. Lung oligometastases were defined as 1-5 metastases confined to the lung while the primary cancer and other metastases were eradicated. Overall survival (OS) and recurrence-free survival (RFS) were estimated for the overall study population and for patients with each type of primary lesion. The OS and RFS rates were compared with those of the patients with any of the other four primary lesion types. Finally, various variables were analyzed to determine what factors influenced OS and RFS. RESULTS The median follow-up was 45.7 months, and the 5-year OS and RFS rates for all 123 patients were 62% and 25%, respectively. The OS time for patients with metastases from CRC was significantly longer (P = .042); it was significantly shorter (P = .022) in patients with metastases from esophageal cancer. Longer disease-free interval was significantly (P = .015) associated with better OS. There was no variable significantly associated with OS and RFS on multivariate analyses. CONCLUSIONS Data from this single-center study appear promising in terms of long-term survival after RF ablation of lung oligometastases from 5 primary lesions.", "qid": 34, "docid": "9ru3gzdc", "rank": 52, "score": 8.481100082397461}, {"content": "Title: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? Content: The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus \u201cSARS-CoV-2\u201d (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect na\u00efve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.", "qid": 34, "docid": "mhytn634", "rank": 53, "score": 8.479000091552734}, {"content": "Title: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? Content: The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus \"SARS-CoV-2\" (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect na\u00efve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.", "qid": 34, "docid": "rhpjosih", "rank": 54, "score": 8.478999137878418}, {"content": "Title: The safety of Pipeline flow diversion in fusiform vertebrobasilar aneurysms: a consecutive case series with longer-term follow-up from a single US center. Content: OBJECT Pessimism exists regarding flow diversion for posterior circulation aneurysms because of reports of perforator territory infarcts and delayed ruptures. The authors report the results of patients who underwent Pipeline Embolization Device (PED) flow diversion using novel strategies for treatment of fusiform posterior circulation aneurysms, and compare these results with those from previously reported series. METHODS The authors conducted a retrospective review of data from consecutive patients with fusiform vertebrobasilar artery aneurysms treated with the PED. RESULTS This review resulted in the identification of 12 such patients (mean [\u00b1 SD] age 55.1 \u00b1 14.1 years). Eleven patients had symptoms; 1 had a dissecting aneurysm identified on imaging for neck pain. The average aneurysm size was 13.25 \u00b1 4.5 mm. None of the aneurysms were ruptured or previously treated. The average clinical follow-up duration was 22.1 \u00b1 10.7 months and radiological follow-up was 14.5 \u00b1 11.1 months from the index PED treatment. One patient suffered a perforator stroke and had a modified Rankin Scale (mRS) score of 4 at last follow-up. Another patient had a retained stent pusher requiring retrieval via surgical cut-down but recovered to an mRS score of 0 at last follow-up. Eleven (91.7%) of 12 patients recovered to an mRS score of 0 or 1. Two patients had aneurysmal remnants at 7 and 10 months, respectively, after the index PED, which were retreated with PEDs. At last follow-up, all 12 aneurysms were occluded and PEDs were patent. The minimum follow-up duration was 12 months from the index PED treatment; no patient experienced delayed hemorrhage, stroke, or in-stent stenosis. CONCLUSIONS Flow diversion with selective adjunctive techniques is evolving to become a safer treatment option for posterior circulation aneurysms. This is the longest clinical follow-up duration reported for a single-center experience of flow-diversion treatment of these aneurysms.", "qid": 34, "docid": "mq3ff34o", "rank": 55, "score": 8.467900276184082}, {"content": "Title: Coronavirus: Short\u2010term pain but strong rebound likely Content: \u25aa Attention has understandably focused on limiting the damage from the short\u2010term effects of the coronavirus outbreak. But it's likely that, once disruption and uncertainty fade, the rebound in activity will be strong. It's important for firms to position themselves for such a recovery. \u25aa Historical evidence supports this view. In the past 200 years, short recessions have typically been followed by robust recovery. Long\u2010term impacts from natural disasters have generally only been evident for specific hazards. Except for AIDS, longer\u2010term pandemic effects also appear to have been contained. \u25aa Surveys during the 2003 SARS and 2009 influenza outbreaks highlight one explanation for time\u2010limited impacts. Public fears increased alongside rising infection rates, but they dissipated promptly as outbreaks came under control. \u25aa Our modelling is consistent with these stylised facts. In our coronavirus pandemic scenario, global growth grinds to a halt in Q2 2020 but then rebounds to a rapid pace within a year. With much of the initial output loss recovered in a relatively short period of time, long\u2010term impacts are limited. \u25aa But there are risks to this view. The period of disruption could be longer than anticipated, depending on the potential spread and seasonality of COVID\u201019 and policy actions to mitigate the fallout. Opinion polls also highlight the potential risk of larger, more persistent effects for some countries. \u25aa Moreover, coronavirus\u2010related weakness and associated financial distress could expose other key vulnerabilities \u2010 for example related to deteriorating corporate sector balance sheets and fragile trade relations. These would be expected to have persistent effects on global activity over the coming years.", "qid": 34, "docid": "jlvvtv52", "rank": 56, "score": 8.443900108337402}, {"content": "Title: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic Content: BACKGROUND: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. FINDINGS: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12\u00b72 years (SD 4\u00b71) to 68\u00b70 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27\u00b79%; 95% CI 20\u00b75-36\u00b70] of 129 patients), depressed mood (42 [32\u00b76%; 24\u00b77-40\u00b79] of 129), anxiety (46 [35\u00b77%; 27\u00b76-44\u00b72] of 129), impaired memory (44 [34\u00b71%; 26\u00b72-42\u00b75] of 129), and insomnia (54 [41\u00b79%; 22\u00b75-50\u00b75] of 129). Steroid-induced mania and psychosis were reported in 13 (0\u00b77%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10\u00b75%; 95% CI 7\u00b75-14\u00b71] of 332 patients), insomnia (34 [12\u00b71%; 8\u00b76-16\u00b73] of 280), anxiety (21 [12\u00b73%; 7\u00b77-17\u00b77] of 171), irritability (28 [12\u00b78%; 8\u00b77-17\u00b76] of 218), memory impairment (44 [18\u00b79%; 14\u00b71-24\u00b72] of 233), fatigue (61 [19\u00b73%; 15\u00b71-23\u00b79] of 316), and in one study traumatic memories (55 [30\u00b74%; 23\u00b79-37\u00b73] of 181) and sleep disorder (14 [100\u00b70%; 88\u00b70-100\u00b70] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32\u00b72% (95% CI 23\u00b77-42\u00b70; 121 of 402 cases from four studies), that of depression was 14\u00b79% (12\u00b71-18\u00b72; 77 of 517 cases from five studies), and that of anxiety disorders was 14\u00b78% (11\u00b71-19\u00b74; 42 of 284 cases from three studies). 446 (76\u00b79%; 95% CI 68\u00b71-84\u00b76) of 580 patients from six studies had returned to work at a mean follow-up time of 35\u00b73 months (SD 40\u00b71). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. INTERPRETATION: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.", "qid": 34, "docid": "853ipgea", "rank": 57, "score": 8.423399925231934}, {"content": "Title: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic Content: BACKGROUND: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I(2) statistics, and assessment of study quality. FINDINGS: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12\u00b72 years (SD 4\u00b71) to 68\u00b70 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27\u00b79%; 95% CI 20\u00b75\u201336\u00b70] of 129 patients), depressed mood (42 [32\u00b76%; 24\u00b77\u201340\u00b79] of 129), anxiety (46 [35\u00b77%; 27\u00b76\u201344\u00b72] of 129), impaired memory (44 [34\u00b71%; 26\u00b72\u201342\u00b75] of 129), and insomnia (54 [41\u00b79%; 22\u00b75\u201350\u00b75] of 129). Steroid-induced mania and psychosis were reported in 13 (0\u00b77%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10\u00b75%; 95% CI 7\u00b75\u201314\u00b71] of 332 patients), insomnia (34 [12\u00b71%; 8\u00b76\u201316\u00b73] of 280), anxiety (21 [12\u00b73%; 7\u00b77\u201317\u00b77] of 171), irritability (28 [12\u00b78%; 8\u00b77\u201317\u00b76] of 218), memory impairment (44 [18\u00b79%; 14\u00b71\u201324\u00b72] of 233), fatigue (61 [19\u00b73%; 15\u00b71\u201323\u00b79] of 316), and in one study traumatic memories (55 [30\u00b74%; 23\u00b79\u201337\u00b73] of 181) and sleep disorder (14 [100\u00b70%; 88\u00b70\u2013100\u00b70] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32\u00b72% (95% CI 23\u00b77\u201342\u00b70; 121 of 402 cases from four studies), that of depression was 14\u00b79% (12\u00b71\u201318\u00b72; 77 of 517 cases from five studies), and that of anxiety disorders was 14\u00b78% (11\u00b71\u201319\u00b74; 42 of 284 cases from three studies). 446 (76\u00b79%; 95% CI 68\u00b71\u201384\u00b76) of 580 patients from six studies had returned to work at a mean follow-up time of 35\u00b73 months (SD 40\u00b71). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. INTERPRETATION: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.", "qid": 34, "docid": "oshov14d", "rank": 58, "score": 8.423398971557617}, {"content": "Title: Hand-assisted technique facilitates preserving graft viability in laparoscopic donor nephrectomy. Content: BACKGROUND To achieve patient safety and minimal operative invasion in living kidney donor nephrectomy, we have performed hand-assisted laparoscopic donor nephrectomy (HALDoN) since 2006. AIM The aim of this study was to evaluate the utility and the technique of HALDoN. METHOD We analyzed 72 donors who underwent HALDoN from February 2008-August 2011. RESULTS Including 8/72 donors who underwent right nephrectomy, all subjects completed HALDoN without conversion to an open procedure. None of the recipients suffered delayed graft function or an ureteric problem. Knife-to-removal time (KRT) was longer among cases with graft weight (GW) >200 g than GW \u2264200 g: 176.5 \u00b1 35.1 minutes vs 142 \u00b1 18.7 minutes (P < .001). Longer KRT (>180 minutes) and right nephrectomy produced longer reperfusion-to-urine secretion time (RUT; P = .002 and P = .027, respectively). Grafts with double renal arteries (N = 10) also tended to show longer RUT (P = .058). In a case with an early renal arterial branch <1 cm from the aorta, we transected the vessel to achieve a single orifice of the artery using a stapling device. At 6 months the average value of decreased renal function of donors had recovered to about 70%. The incidence of complication was 8.3% but there was no life-threatening morbidity. CONCLUSION The hand-assisted method could make the operating surgeon more confident to perform laparoscopic donor nephrectomy safely. HALDoN offers particular advantages for precise dissection using finger retraction and control of potential bleeding in the stages of vascular stapling and graft removal, preserving graft viability.", "qid": 34, "docid": "248uofgi", "rank": 59, "score": 8.405200004577637}, {"content": "Title: Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China Content: OBJECTIVE: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. METHODS: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. RESULTS: We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year; 95%CI: 1.11-1.16), and being male (OR 1.83; 95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. CONCLUSIONS: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.", "qid": 34, "docid": "1n7dx35k", "rank": 60, "score": 8.394399642944336}, {"content": "Title: Does immune privilege result in recovered patients testing positive for COVID-19 again? Content: Recently, an increasing number of reports have indicated that a few patients who were believed to have recovered from COVID-19 initially tested negative but later tested positive. Several hospitals in different countries have detected SARS-CoV-2 RNA in the semen and cerebrospinal fluid of patients with severe COVID-19. Given the fact that the testes and central nervous system are both immune privilege sites and the fact that Ebola virus and Zika virus can avoid immune clearance and continue proliferating and spreading by hiding in those sites, the question of whether SARS-CoV-2 is present in immune privilege sites, it attacks those sites, and it spreads again after proliferating in those sites needs to be investigated.", "qid": 34, "docid": "ocdyqqqw", "rank": 61, "score": 8.371600151062012}, {"content": "Title: Healthcare workers experiences of working on the frontline and views about support during COVID-19 and comparable pandemics: A rapid review and meta-synthesis Content: Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline healthcare workers and growing calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers own perspectives or what their views are about support. This rapid review identified 40 qualitative studies which have explored healthcare workers experiences and views from previous pandemics, including and comparable to COVID-19. Meta-synthesis of this qualitative data using thematic analysis derived eight key themes which transcended pandemics, time, and geographical boundaries. This pandemic is not unprecedented; the themes that arose from previous pandemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of these previous pandemics, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.", "qid": 34, "docid": "6gc7smqf", "rank": 62, "score": 8.368800163269043}, {"content": "Title: Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China Content: BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 \u00b1 9.3 vs 12.2 \u00b1 4.6 d in the control group) and a longer course of illness (35.3 \u00b1 8.3 vs 18.8 \u00b1 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.", "qid": 34, "docid": "7pd7dtuw", "rank": 63, "score": 8.35099983215332}, {"content": "Title: Improved survival outcome in SARs-CoV-2 (COVID-19) Acute Respiratory Distress Syndrome patients with Tocilizumab administration Content: ABSTRACT Background: The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), was declared a global pandemic by the World Health Organization on March 11, 2020. Hence, there is an urgency to find effective treatment. Of those patients afflicted in the United States, many have required treatment with ventilator secondary to acute respiratory distress syndrome (ARDS). Data are needed regarding the benefit of treatment and prevention of the cytokine storms in COVID-19 patients with Tocilizumab. Methods: Clinical outcomes data for patients admitted to Orange Regional Medical Center with confirmed COVID-19 from Mar 15, 2020 to Apr 20, 2020 were identified through electronic health record chart review. We conducted a retrospective case-control study in confirmed COVID 19 positive patients with ARDS requiring mechanical ventilation and compared outcome in terms of mortality and length of stay amongst those who received Tocilizumab as treatment modality opposed to those that did not. Results: A total of 94 patients with COVID-19 ARDS were analyzed. 44 were in the study group and 50 in the control group. We tried to match both group as close as possible in terms of age, sex, BMI and HS score- calculated using inflammatory markers- ferritin, triglycerides, AST and fibrinogen. The median age was 55.5 years in the study group and 66 in the control group, difference was not statistically significant. Average HS score was 114 in the Tocilizumab group and 92 in the control group, difference was statistically significant with P<0.0001. Also, the patients in the study group had elevated levels of IL-6, triglycerides, AST, ferritin which were statistically significant with p < 0.0001 when compared to the control group. Length of stay was longer, average 17.9 days in the Tocilizumab. Survival rate was much lower at 48 % in the control group and 61.36 % in patients who received Tocilizumab with significant P value of < 0.00001. The number needed to treat (NNT) was 7.48, if we treat 8 patients with Tocilizumab, 1 will not die. Conclusions: Cytokine Release Syndrome (CRS) occurs in a large number of patients with severe COVID-19, which is also an important cause of death. IL- 6 is the key molecule of CRS, so IL-6R antagonist Tocilizumab may be of value in improving outcomes. In our study Tocilizumab group seemed to have improved survival outcome. Results have to be interpreted with caution since this is a retrospective study and mortality is affected by multiple, confounding factors. We await the results of ongoing randomized controlled trials to definitely answer the question of whether Tocilizumab improves survival in COVID-19 ARDS patients.", "qid": 34, "docid": "m7aworz8", "rank": 64, "score": 8.338000297546387}, {"content": "Title: Short-term outcomes for robotic colorectal surgery by provider volume. Content: BACKGROUND There has been a rapid increase in robotic colorectal surgery. Benefits of this technology are unclear and being investigated. However, differences in outcomes between centers have not been evaluated. Our aim was to evaluate outcomes for robotic colorectal procedures by surgeon and hospital volume. STUDY DESIGN A national inpatient database was reviewed for robotic colorectal resections performed during an 18-month period. Hospitals and surgeons were stratified into high, average, and low case volumes based on a normal distribution scale. High, average, and low volume was defined as \u2264 10, 11 to 20, and >20, respectively, for hospitals, and \u2264 5, 6 to 15, and >15, respectively, for surgeons. Short-term outcomes and hospital cost were evaluated. RESULTS There were 1,428 robotic colorectal cases across 123 hospitals and 411 surgeons evaluated. Only 13% (n = 16) of hospitals and 4.4% (n = 18) of surgeons performed a high volume of robotic colorectal cases. Lower volume was associated with significantly more overall complications (p < 0.001; p < 0.001), longer length of stay (p = 0.005; p < 0.001), and higher cost (p < 0.001; p < 0.001) at the hospital and surgeon level, respectively. High-volume hospitals and surgeons had significantly lower rates of postoperative bleeding (p < 0.001; p < 0.001) and ileus (p = 0.003; p = 0.0014). CONCLUSIONS Lower-volume providers, who are performing the majority of procedures, are generating more complications, longer hospital lengths of stay, and higher costs of care. These results have a negative impact on quality outcomes measures for those facilities. Although surgeons and hospitals continue to selectively explore robotics, this should be limited to high volume and interested surgeons and hospitals to offer high-quality outcomes to patients.", "qid": 34, "docid": "wfgrqjn4", "rank": 65, "score": 8.318699836730957}, {"content": "Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust. Content: A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years and have brought important new players into the field of health estimate production. These changes have rekindled debates about the validity and legitimacy of global health estimates. This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political, and ideational contexts, which vary at different levels of the global health architecture. Broadly, most global health estimates tend to be made far from the localities where the data upon which they are based are collected and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals. Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs and that fit with local ideas of what is credible and useful - in other words, data that are both technically and socially robust for those who make key decisions about health. We suggest that greater engagement of local actors (and local data) in the formulation, communication, and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term. Besides strengthening national information systems, this requires ongoing interaction, building trust, and establishing a communicative infrastructure. Local capacities to use knowledge to improve health must be supported.", "qid": 34, "docid": "iig60vp7", "rank": 66, "score": 8.304300308227539}, {"content": "Title: Searching for a coronavirus cure in the blood Content: The blood of people who have recovered from COVID-19 may be the world\u2019s most sought-after substance right now It contains a stockpile of antibodies made by immune cells that have successfully mounted an attack on the invading virus, SARS-CoV-2 While multiple efforts are focusing on repurposing existing drugs, like remdesivir or chloroquine, to fight this new virus, many scientists think that the fastest route to novel therapies specifically designed to treat the infection could come by harvesting those antibodies These antibody-based therapies could take many forms The simplest, and the only that is already being tested in people with COVID-19, is convalescent plasma, the antibody-rich portion of blood donated from someone who recovered from the disease At the other end of the spectrum, companies are meticulously analyzing plasma from recovered humans or immunized animals to select the very best antibodies, which they can use to manufacture traditional monoclonal antibody therapies These approaches, and others in between, are barreling toward the clinic at a pandemic pace", "qid": 34, "docid": "nxaoh7gg", "rank": 67, "score": 8.282099723815918}, {"content": "Title: Intestinal/Multivisceral Transplantation Content: Intestinal/multivisceral transplantation has evolved from an experimental procedure to the treatment of choice for patients with irreversible intestinal failure and serious complications related to long-term parenteral nutrition. Children who are likely to suffer permanent intestinal failure and benefit from intestinal transplantation include those with a remaining small bowel length of less than 30\u201340 cm, absence of the ileocecal valve, colonic resection and malabsorptive syndromes. Indications for transplant include frequent severe bouts of catheter associated sepsis, threatened loss of vascular access and the development of liver cirrhosis from cholestasis. Children who are more likely to experience cholestasis from total parenteral nutrition include those who experience persistent hyperbilirubinemia (greater than 6 mg/dl despite enteral nutrition), those with recurrent sepsis and/or bacterial overgrowth and those with minimal tolerance of any enteral feeds in the first few months post resection. The 1 year survival rate after intestinal transplantation has markedly improved over the last several years but long term survival rates have remained unchanged. The improved short term survival rates have led to an increased prevalence of this patient population in intensive care units. Management of intestinal and multivisceral transplant recipients is uniquely challenging because of complications arising from the high incidence of transplant rejection and its treatment. In the ICU, the complexity of medical care for the transplant recipient requires a multidisciplinary approach with coordination by an intensivist in collaboration with the transplant surgeon, gastroenterologist, and other specialists.", "qid": 34, "docid": "5iofpvx2", "rank": 68, "score": 8.268600463867188}, {"content": "Title: COVID\u201019 Pandemic and Its Impact on the Global Economy: What Does It Take to Turn Crisis into Opportunity? Content: The COVID\u201019 pandemic broke out at a time when there were heightened uncertainties in the global economy. Understanding these uncertainties provides an important background for analyzing the impact of the pandemic on the global economy, assessing the effectiveness of those policy measures in combating the pandemic and reviving the global economy, and predicting the trajectory of the economic recovery in post\u2010pandemic era. We analyze how COVID\u201019 would likely deepen some existing malaise in the global economy, and what could be done to redress these problems while managing economic recovery from the crisis and beyond. We argue that three fundamental factors which could lead to a solid recovery in the post pandemic era are structural reform, new technology and re\u2010integration which could be managed through instituting a new \u201cglobal social contract.\u201d Supported by strong public policies at all levels especially at national levels, the tripartite could serve as salvation of the global economy recovering or re\u2010emerging from this pandemic crisis.", "qid": 34, "docid": "hgsckys9", "rank": 69, "score": 8.26039981842041}, {"content": "Title: A short or a long Roux limb in gastric bypass surgery: does it matter? Content: BACKGROUND The Roux-en-Y gastric bypass (RYGB) still remains the gold standard in bariatric surgery. However, no consensus exists on the optimal limb lengths to induce maximum weight reduction. The aim of the present study was to assess the effect of a longer alimentary limb (AL) length on weight reduction after RYGB. METHODS A retrospective analysis of a prospectively collected database of patients who underwent a primary laparoscopic RYGB between January 2001 and March 2011 was performed. Patients received a short AL (SAL; 100 cm) or a long AL (LAL; 150 cm). Primary outcome was weight loss, and secondary outcomes were short- and long-term complication rates. RESULTS A total of 768 patients received a RYGB during the study period. Of these, 730 consecutive patients were included for long-term analysis and had a mean follow-up (FU) of 37 \u00b1 26 [range 0-120] months; 360 (47 %) patients received a SAL RYGB. Overall %TBWL was 33 \u00b1 9 % after 2 years (FU 74 %) and 28 \u00b1 12 % after 5 years (FU 20 %). No significant differences in %TBWL were found between SAL RYGB and LAL RYGB during the study period. The 30-day mortality rate was 0.13, 9 % overall short-term complication rate and 19 % cumulative long-term complication rate. No differences in complications were found between SAL and LAL RYGB patients. CONCLUSION Lengthening of the alimentary limb from 100 to 150 cm did not affect post-RYGB weight loss. Overall complication rates were low and comparable in this series of RYGB patients.", "qid": 34, "docid": "404fkbpx", "rank": 70, "score": 8.245400428771973}, {"content": "Title: Characteristics and serological patterns of COVID\u201019 convalescent plasma donors: optimal donors and timing of donation Content: BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID\u201019) has led to the exploratory use of convalescent plasma for treating COVID\u201019. Case reports and case series have shown encouraging results. This study investigated SARS\u2010CoV\u20102 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID\u201019 patients, aged 18\u201055 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS\u2010CoV\u20102 N\u2010specific IgM, IgG, and S\u2010RBD\u2010specific IgG levels were measured by enzyme\u2010linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N\u2010specific IgM antibody declined after recovery, S\u2010RBD\u2010specific and N\u2010specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5\u00b0C or lasting longer than 3 days exhibited higher levels of S\u2010RBD\u2010specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S\u2010RBD\u2010specific IgG titer of \u22651:160 and 78% had a titer of \u22651:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5\u00b0C, 100% had an S\u2010RBD\u2010specific IgG titer of \u22651:160 and 93% had a titer of \u22651:640. CONCLUSION: This study indicates that the S\u2010RBD\u2010specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID\u201019 symptoms. We recommend the following selection criteria for optimal donation of COVID\u201019 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5\u00b0C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S\u2010RBD\u2010specific IgG titers.", "qid": 34, "docid": "9rca92j5", "rank": 71, "score": 8.239999771118164}, {"content": "Title: Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation Content: BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5\u00b0C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of &#8805;1:160 and 78% had a titer of &#8805;1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5\u00b0C, 100% had an S-RBD-specific IgG titer of &#8805;1:160 and 93% had a titer of &#8805;1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5\u00b0C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.", "qid": 34, "docid": "px00uyo3", "rank": 72, "score": 8.239998817443848}, {"content": "Title: Encountering COVID-19 as Endocrinologists. Content: The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.", "qid": 34, "docid": "bqm6ty79", "rank": 73, "score": 8.21560001373291}, {"content": "Title: Encountering COVID-19 as Endocrinologists Content: The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.", "qid": 34, "docid": "n4gece0x", "rank": 74, "score": 8.215599060058594}, {"content": "Title: Differences of SARS-CoV-2 Shedding Duration in Sputum and Nasopharyngeal Swab Specimens among Adult Inpatients with COVID-19 Content: Abstract Background The viral shedding duration of SARS-CoV-2 has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of COVID-19. Research Question What are the shedding durations of SARS-CoV-2 RNA in upper and lower respiratory tract specimens respectively? What are their associated risk factors? Study Design and Methods: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020 to March 20, 2020 were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis. Results SARS-CoV-2 RNA was detected from NPS in 48 (70.6%) patients, and from sputum specimens in 30 (44.1%) patients. The median duration of viral shedding from sputum specimens (34 days, IQR 24-40 days) was significantly longer than from NPS (19 days, IQR 14-25 days; P<0.001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (HR 1.71, 1.01-2.93). It was noteworthy that in 9 patients the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum. Interpretation These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration.", "qid": 34, "docid": "cuw1aowj", "rank": 75, "score": 8.203800201416016}, {"content": "Title: What Matters Most for Treatment Decisions in Hepatitis C: Effectiveness, Costs, and Altruism. Content: OBJECTIVE Comparative evaluations of innovations in hepatitis C virus (HCV) drug therapy typically focus on sustained virologic response (SVR) without addressing psychological and socioeconomic challenges that extend beyond virologic cure. This study aims to identify and prioritize variables important to patients when making the decision to start HCV treatment. METHODS A three-round Delphi process was conducted with the first round derived from a systematic literature review and advisory board input, including patients who have been affected by HCV, physicians, pharmacists, and a patient group representative. Delphi panelists were HCV patients who had received treatment or were considering treatment. Panelists were asked about factors influencing their HCV treatment decisions. Thematic analysis of open-ended responses based on grounded theory was used. Agreement with each category and rankings based on order of importance from the patient perspective was reported. RESULTS Treatment effectiveness (100% agreement), longer life (88%), fear of complications (84%), financial issues (80%), quality of life (100%), and impact on society (80%) were considered important factors to patients in decisions to seek treatment. A fear of harming others (87%) was considered more important than physical symptoms (83%) in terms of patient-reported problems caused by HCV. Medication costs (91%) were identified as the most important costs of having HCV, followed by doctor costs (77%). CONCLUSIONS In addition to treatment effectiveness, patient experiences with financial problems, quality of life, and altruistic desires impact HCV patients' decisions. The risk of infecting others may motivate patients to seek treatment as much as personally experienced physical symptoms.", "qid": 34, "docid": "j7xlwlc2", "rank": 76, "score": 8.189399719238281}, {"content": "Title: Clinical and radiological outcome following pneumothorax after endoscopic lung volume reduction with valves. Content: INTRODUCTION Valve implantation has evolved as a therapy for patients with advanced emphysema. Although it is a minimally invasive treatment, it is associated with complications, the most common being pneumothorax. Pneumothorax occurs due to the rapid target lobe volume reduction and may be a predictor of clinical benefit despite this complication. OBJECTIVE The objective of this study was to conduct an exploratory data analysis of patients who developed a pneumothorax following endoscopic valve therapy for emphysema. MATERIALS AND METHODS This study performed a retrospective evaluation of pneumothorax management and the impact of pneumothorax on clinical outcomes in 70 patients following valve therapy in 381 consecutive patients. RESULTS Pneumothorax rate following valve therapy was 18%. Pneumothorax management consisted of chest tube insertion, valve removal, and surgical intervention in 87% (61/70), 44% (31/70), and 19% (13/70) of the patients, respectively. Despite pneumothorax, patients experienced modest but significant improvements in lung function parameters (forced expiratory volume in 1 second: 55\u00b1148 mL, residual volume: -390\u00b1964 mL, total lung capacity: -348\u00b1876; all P<0.05). Persistent lobar atelectasis 3 months after recovering from pneumothorax, which was associated with relevant clinical improvement, was observed in only 21% (15/70) of the patients. CONCLUSION Pneumothorax is a frequent severe complication following valve therapy that requires further intervention. Nevertheless, the pneumothorax does not impair the clinical status in the majority of patients. Patients with lobar atelectasis benefit after recovering from pneumothorax in terms of lung function parameters.", "qid": 34, "docid": "xy5cn4rv", "rank": 77, "score": 8.184499740600586}, {"content": "Title: Clinical outcomes and immunologic characteristics of Covid-19 in people with HIV Content: We performed a retrospective study of Covid-19 in people with HIV (PWH). PWH with Covid-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin-6, interleukin-8, and TNF-alpha were commonly elevated. In all, 19/72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of Covid-19 despite ART and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.", "qid": 34, "docid": "qyo9x78w", "rank": 78, "score": 8.16469955444336}, {"content": "Title: Long-term production effects of clinical cryptosporidiosis in neonatal calves Content: Abstract Cryptosporidiosis can have a devastating effect in neonatal calves, resulting in diarrhoea, dehydration and, in severe cases, death of the animal. The disease is caused by Cryptosporidium spp. and is one of the most common causes of calf enteritis in the UK. The parasite is very difficult to remove from the farm, as the oocysts have a tough outer wall which enables the parasite to survive for several months in moist temperate environmental conditions and it is difficult to kill oocysts with common disinfectants used on a farm. If appropriate management practises are applied, the disease is usually self-limiting and most calves will recover. It has been shown, in studies with children and in lambs, that severe clinical cryptosporidiosis can result in long-term growth and cognitive impairment compared with individuals with no obvious signs of the disease. This study measured the long-term growth rate of beef calves on farm by comparing groups of animals that had suffered differing degrees of clinical severity of cryptosporidiosis as neonates. A group of 27 beef calves were enrolled in the study and monitored from birth to 6 months of age. The calves were scored for severity of cryptosporidiosis and weighed at regular intervals. The average difference in weight gain, at 6 months, between a group of calves that had severe cryptosporidiosis as neonates and a group of calves with no clinical signs of infection was 34 kg. Those calves that had experienced severe cryptosporidiosis as neonates showed a significantly reduced live weight gain compared with those calves showing no clinical signs of infection (P = 0.034). Therefore, the impact of severe cryptosporidiosis in neonatal calves has longer term effects on weight gain and production efficiency, resulting in the parasite having a greater impact on cattle production than previously thought.", "qid": 34, "docid": "wdpgo5km", "rank": 79, "score": 8.130499839782715}, {"content": "Title: Health Equity, Social Policy, and Promoting Recovery from COVID-19. Content: The COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic inequality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, we must look both upstream and abroad for inspiration. In this essay, I argue for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave, upgraded wage insurance policies, tax reform, investments in parental leave, child care, and education, and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity will also improve population health and economic performance and allow us to confront future pandemics more successfully.", "qid": 34, "docid": "1ihm08gq", "rank": 80, "score": 8.128000259399414}, {"content": "Title: Health Equity, Social Policy, and Promoting Recovery from COVID-19 Content: The COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic inequality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, we must look both upstream and abroad for inspiration. In this essay, I argue for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave, upgraded wage insurance policies, tax reform, investments in parental leave, child care, and education, and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity will also improve population health and economic performance and allow us to confront future pandemics more successfully.", "qid": 34, "docid": "pyzh9fo8", "rank": 81, "score": 8.127999305725098}, {"content": "Title: Quantifying Projected Impact of Social Distancing Policies on COVID-19 Outcomes in the US Content: Current social distancing measures to impede COVID-19 (such as shelter-in-place) are economically unsustainable in the long term. Models are needed to understand the implications of possible relaxation options for these measures. We report such models, together with corresponding parameter estimation techniques and prediction outcomes, borrowing insights from another domain; namely, information cascades. Our models assume that the containment of the virus into isolated locales is no longer possible. Instead, we explore options that reduce the rate of spread. We predict COVID-19 contagion trends in different geographic regions under a\"what if\"scenario to understand the effects of potential policy decisions on regional trends. Our model allows experimentation with other policies that, we hope, can contribute to socially viable outcomes both in terms of health system capacity and economic impact. We apply our model to over 30 highly impacted states in the US and publish the results at https://covid19predictions.csl.illinois.edu/", "qid": 34, "docid": "5rz7gk3m", "rank": 82, "score": 8.119400024414062}, {"content": "Title: COVID-19: The potential treatment of pulmonary fibrosis associated with SARS-CoV-2 infection Content: In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients\u2019 quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.", "qid": 34, "docid": "4b45gh77", "rank": 83, "score": 8.11769962310791}, {"content": "Title: The Decreasing Incidence of Acute Appendicitis During COVID-19: A Retrospective Multi-centre Study Content: BACKGROUND: As the novel coronavirus disease 19 (COVID-19) spreads, a decrease in the number of patients with acute appendicitis (AA) has been noted in our institutions. The aim of this study was to compare the incidence and severity of AA before and during the COVID-19 pandemic. METHODS: A retrospective cohort analysis was performed between December 2019 and April 2020 in the four high-volume centres that provide health care to the municipality of Jerusalem, Israel. Two groups were created. Group A consisted of patients who presented in the 7 weeks prior to COVID-19 first being diagnosed, whilst those in the 7 weeks after were allocated to Group B. A comparison was performed between the clinicopathological features of the patients in each group as was the changing incidence of AA. RESULTS: A total of 378 patients were identified, 237 in Group A and 141 in Group B (62.7% vs. 37.3%). Following the onset of COVID-19, the weekly incidence of AA decreased by 40.7% (p = 0.02). There was no significant difference between the groups in terms of the length of preoperative symptoms or surgery, need for postoperative peritoneal drainage or the distribution of complicated versus uncomplicated appendicitis. CONCLUSIONS: The significant decrease in the number of patients admitted with AA during the onset of COVID-19 possibly represents successful resolution of mild appendicitis treated symptomatically by patients at home. Further research is needed to corroborate this assumption and identify those patients who may benefit from this treatment pathway.", "qid": 34, "docid": "yro3xoh4", "rank": 84, "score": 8.115599632263184}, {"content": "Title: Cardiac complications in community-acquired pneumonia and COVID-19 Content: Community-acquired pneumonia (CAP) remains a global health problem with significant morbidity and mortality. Much recent published literature about the infection has indicated that a substantial number of patients with CAP, particularly those ill enough to be admitted to hospital, will suffer a cardiovascular event. While these may include events such as deep venous thrombosis and stroke, most of the events involve the heart and include the occurrence of an arrhythmia (most commonly atrial fibrillation), new onset or worsening of heart failure and acute myocardial infarction. While such cardiac events may occur, for example, in all-cause CAP and CAP due to influenza virus infection, and more recently described with the SARS-CoV-2 pandemic, a significant amount of research work has been investigating the pathogenic mechanisms of these cardiac events in patients with CAP due to Streptococcus pneumoniae (pneumococcus) and, more recently, COVID-19 infections. Such research has identified a number of mechanisms by which these microorganisms may cause cardiovascular events. Importantly, these cardiac events appear not only to be associated with in-hospital mortality, but they also appear to contribute to longer-term mortality of patients with CAP, even after their discharge from hospital. This review will focus initially on studies of cardiovascular events in all-cause CAP and pneumococcal CAP, excluding COVID-19 infection, and then address similar issues in the latter infection.", "qid": 34, "docid": "k0kud80s", "rank": 85, "score": 8.096500396728516}, {"content": "Title: Differences of SARS-CoV-2 Shedding Duration in Sputum and Nasopharyngeal Swab Specimens Among Adult Inpatients With COVID-19 Content: BACKGROUND: The viral shedding duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of coronavirus disease 2019 (COVID-19). RESEARCH QUESTION: What are the shedding durations of SARS-CoV-2 RNA in the upper and lower respiratory tract specimens? What are their associated risk factors? STUDY DESIGN AND METHODS: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020, to March 20, 2020, were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis. RESULTS: SARS-CoV-2 RNA was detected from NPSs in 48 patients (70.6%), and from sputum specimens in 30 patients (44.1%). The median duration of viral shedding from sputum specimens (34 days; interquartile range [IQR], 24-40) was significantly longer than from NPSs (19 days; IQR, 14-25; P < .001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (hazard ratio, 1.71; 95% CI, 1.01-2.93). It was noteworthy that in 9 patients, the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum. INTERPRETATION: These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration.", "qid": 34, "docid": "f5scvnpf", "rank": 86, "score": 8.095600128173828}, {"content": "Title: A mathematical model to guide the re-opening of economies during the COVID-19 pandemic Content: Despite rigorous global containment and quarantine efforts, the incidence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19, continues to surge, with more than 12 million laboratory-confirmed cases and over 500,000 deaths worldwide (as of 11 July 2020). Aside from the continued surge in cases and the imperatives of public health concern and saving lives, economic devastation is also mounting with a global depression now seeming inevitable. There is limited attention directed towards people who have recovered from the virus and whether this metric can be useful in guiding when the economy can be re-opened. In this paper, a simpler model is presented in order to guide various countries on the (possible) re-opening of the economy (or re-opening in stages/phases) alongside risk categories and ratios. Factors that need to be considered when applying the model include the healthcare capacity in terms of the number of hospitals, beds and healthcare workers that are available to capacitate this virus. In addition, population size, physical distancing measures, socio-economic disparities, lockdown regulations in each country, and more importantly - the amount and accuracy of testing conducted, is also imperative to consider. Decisions adopted by leaders around the world have the most difficult decision to make (yet), and have to weigh up on what really matters; health or wealth. It is suggested that this model be applied in a number of states/counties and countries in order to gauge the risk of their location being re-opened, by observing their total number of recoveries in proximity to total number of cases.", "qid": 34, "docid": "q5efqr7r", "rank": 87, "score": 8.077799797058105}, {"content": "Title: Predictions, role of interventions and effects of a historic national lockdown in India's response to the COVID-19 pandemic: data science call to arms Content: Importance: India has taken strong and early public health measures for arresting the spread of the COVID-19 epidemic. With only 536 COVID-19 cases and 11 fatalities, India - a democracy of 1.34 billion people - took the historic decision of a 21-day national lockdown on March 25. The lockdown was further extended to May 3, soon after the analysis of this paper was completed. Objective: To study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 cases in India compared to other less severe non-pharmaceutical interventions using epidemiological forecasting models and Bayesian estimation algorithms; to compare effects of hypothetical durations of lockdown from an epidemiological perspective; to study alternative explanations for slower growth rate of the virus outbreak in India, including exploring the association of the number of cases and average monthly temperature; and finally, to outline the pivotal role of reliable and transparent data, reproducible data science methods, tools and products as we reopen the country and prepare for a post lock-down phase of the pandemic. Design, Setting, and Participants: We use the daily data on the number of COVID-19 cases, of recovered and of deaths from March 1 until April 7, 2020 from the 2019 Novel Coronavirus Visual Dashboard operated by the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE). Additionally, we use COVID-19 incidence counts data from Kaggle and the monthly average temperature of major cities across the world from Wikipedia. Main Outcome and Measures: The current time-series data on daily proportions of cases and removed (recovered and death combined) from India are analyzed using an extended version of the standard SIR (susceptible, infected, and removed) model. The eSIR model incorporates time-varying transmission rates that help us predict the effect of lockdown compared to other hypothetical interventions on the number of cases at future time points. A Markov Chain Monte Carlo implementation of this model provided predicted proportions of the cases at future time points along with credible intervals (CI). Results: Our predicted cumulative number of COVID-19 cases in India on April 30 assuming a 1-week delay in people's adherence to a 21-day lockdown (March 25 - April 14) and a gradual, moderate resumption of daily activities after April 14 is 9,181 with upper 95% CI of 72,245. In comparison, the predicted cumulative number of cases under \"no intervention\" and \"social distancing and travel bans without lockdown\" are 358 thousand and 46 thousand (upper 95% CI of nearly 2.3 million and 0.3 million) respectively. An effective lockdown can prevent roughly 343 thousand (upper 95% CI 1.8 million) and 2.4 million (upper 95% CI 38.4 million) COVID-19 cases nationwide compared to social distancing alone by May 15 and June 15, respectively. When comparing a 21-day lockdown with a hypothetical lockdown of longer duration, we find that 28-, 42-, and 56-day lockdowns can approximately prevent 238 thousand (upper 95% CI 2.3 million), 622 thousand (upper 95% CI 4.3 million), 781 thousand (upper 95% CI 4.6 million) cases by June 15, respectively. We find some suggestive evidence that the COVID-19 incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with Pearson correlation estimates [95% confidence interval] between average monthly temperature and total monthly incidence around the world being -0.185 [-0.548, 0.236] for January, -0.110 [-0.362, 0.157] for February, and -0.173 [-0.314, -0.026] for March. Conclusions and Relevance: The lockdown, if implemented correctly in the end, has a high chance of reducing the total number of COVID-19 cases in the short term, and buy India invaluable time to prepare its healthcare and disease monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. We cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. From an epidemiological perspective, a longer lockdown between 42-56 days is preferable. However, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. Data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. Software: Our contribution to data science includes an interactive and dynamic app (covind19.org) with short- and long-term projections updated daily that can help inform policy and practice related to COVID-19 in India. Anyone can visualize the observed data for India and create predictions under hypothetical scenarios with quantification of uncertainties. We make our prediction codes freely available (https://github.com/umich-cphds/cov-ind-19) for reproducible science and for other COVID-19 affected countries to use them for their prediction and data visualization work.", "qid": 34, "docid": "3a3c8ee1", "rank": 88, "score": 8.063199996948242}, {"content": "Title: Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study Content: Background: COVID-19 is an emerging disease caused by the SARS-CoV-2 virus; no specific medication has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19. Methods: This single-center, retrospective, and observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Demographic information, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and eight patients with mild and severe symptoms, respectively. Findings: All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all eight severe-group patients (median treatment: 17.5 days; four received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all eight in the severe group (median treatment: 9 days; two received linezolid). Moreover, seven patients (12.72%) were treated with glucocorticoids and nine (16.36%) with immunomodulators. Interpretation: Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary.", "qid": 34, "docid": "hc0za6fh", "rank": 89, "score": 8.0600004196167}, {"content": "Title: Laparoscopic surgical treatment of ileocecal Crohn's disease: Impact of obesity on short term results. Content: INTRODUCTION The aim of our study was to analyse the short-term outcomes of laparoscopic surgery for a no medical responding ileocolic Cohn's disease in a single centre according to the presence of obesity. METHODS A cross-sectional study was performed including all consecutive patients who underwent laparoscopic resection for ileocecal Crohn's disease from November 2006 to November 2015. Patients were divided according to body mass index \u2265 30 kg/m2 in order to study influence of obesity in the short-term outcomes. The following variables were studied: characteristics of patients, surgical technique and postoperative results (complications, reintervention, readmission and mortality) during first 30 postoperative days. RESULTS A total of 100 patients were included (42 males) with a mean age of 39.7\u00b115.2 years (range 18-83). The overall complication rate was 20% and only 3 patients had an anastomotic leak. Seven patients needed reoperation in the first 30 days postop (7%). The median postoperative length of hospitalization was 5.0 days. Operative time was significantly longer in patients with obesity (130 vs. 165minutes, P=.007) but there were no significant differences among the postoperative results in patients with and without obesity. CONCLUSIONS This study confirmed that laparoscopic approach for ileocecal Cohn's disease is a safety and feasible technique in patients with obesity. In this last group of patients we only have to expect a longer operative time.", "qid": 34, "docid": "ktcjgnka", "rank": 90, "score": 8.057999610900879}, {"content": "Title: Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model Content: The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.", "qid": 34, "docid": "hcla915y", "rank": 91, "score": 8.054200172424316}, {"content": "Title: Measuring COVID-19 and Influenza in the Real World via Person-Generated Health Data Content: Background: Since the beginning of the COVID-19 pandemic data from smartphones and connected sensors has been used to learn about symptoms presentation and management outside the clinic walls. However, reports on the validity of such data are still sparse, especially when it comes to symptom progression and relevance of wearable sensors. Objective: To understand the relevance of Person-GeneratedHealth Data (PGHD) as a means for early detection, monitoring and management of COVID-19 in everyday life. This includes quantifying prevalence and progression of symptoms from self-reports as well as changes in activity and physiological parameters continuously measured from wearable sensors, and contextualizing findings for COVID-19 patients with those from cohorts of flu patients. Design, Setting, and Participants: Retrospective digital cohort study of individuals with a self-reported positive SARS-CoV-2 or influenza test followed over the period 2019-12-02 to2020-04-27. Three cohorts were derived: Patients who self-reported being diagnosed with flu prior to the SARS-CoV-2 pandemic (N=6270, of which 1226 also contributed sensorPGHD); Patients who reported being diagnosed with flu during the SARS-CoV-2 pandemic (N=426, of which 85 also shared sensor PGHD); and patients who reported being diagnosed withCOVID-19 (N=230, of which sensor PGHD was available for 41).The cohorts were derived from a large-scale digital participatory surveillance study designed to track Influenza-like Illness(ILI) incidence and burden over time. Exposures: Self-reported demographic data, comorbidities, and symptoms experienced during a diagnosed ILI episode, including SARS-CoV-2.Physiological and behavioral parameters measured daily from commercial wearable sensors, includingResting Heart Rate (RHR), total step count, and nightly sleep hours. Main Outcomes and Measures: We investigated the percent-age of individuals experiencing symptoms of a given type (e.g.shortness of breath) across demographic groups and over time. We examined illness duration, and care seeking behavior, and how RHR, step count, and nightly sleep hours deviated from expected behavior on healthy days over the course of the infection episode. Results: Self-reported symptoms of COVID-19 present differently from flu. COVID-19 cases tended to last longer than flu(median of 12 vs. 9 days), are uniquely characterized by chest pain/pressure, shortness of breath, and anosmia. The fraction of elevated RHR measurements collected daily from commercial wearable devices rise significantly in the 2 days surrounding ILI symptoms onset, but does not appear to do so in a way specific to COVID-19. Steps lost due to COVID-19 persists for longer. Conclusion and Relevance: PGHD can be a valid source of longitudinal real world data to detect and monitor COVID-19-related symptoms and behaviors at population scale. PGHD may provide continuous, near realtime feedback to intervention effectiveness that otherwise requires waiting for symptoms to develop into contacts with the healthcare system. It has also the potential to increase pre-test probability of other downstream diagnostics. To effectively leverage PGHD for participatory surveillance it is crucial to invest in the creation of trusted, long-term communication channels with individuals through whichdata can be efficiently collected, consented, and contextualized,while protecting the privacy of individuals and ultimately facilitating the transition in and out of care.", "qid": 34, "docid": "2bz9u8k0", "rank": 92, "score": 8.05109977722168}, {"content": "Title: Being HIV positive and staying on antiretroviral therapy in Africa: A qualitative systematic review and theoretical model. Content: BACKGROUND Adherence to antiretroviral therapy (ART) and long-term uninterrupted engagement in HIV care is difficult for HIV-positive people, and randomized trials of specific techniques to promote adherence often show small or negligible effects. Understanding what influences decision-making in HIV-positive people in Africa may help researchers and policy makers in the development of broader, more effective interventions and policies. METHODS We used thematic synthesis and a grounded theory approach to generate a detailed narrative and theoretical model reflecting life with HIV in Africa, and how this influences ART adherence and engagement decisions. We included qualitative primary studies that explored perspectives, perceptions and experiences of HIV-positive people, caregivers and healthcare service providers. We searched databases from 1 January 2013 to 9 December 2016, screened all studies, and selected those for inclusion using purposeful sampling methods. Included studies were coded with Atlas.ti, and we assessed methodological quality across five domains. RESULTS We included 59 studies from Africa in the synthesis. Nine themes emerged which we grouped under three main headings. First, people who are HIV-positive live in a complicated world where they must navigate the challenges presented by poverty, competing priorities, unpredictable life events, social identity, gender norms, stigma, and medical pluralism-these influences can make initiating and maintaining ART difficult. Second, the health system is generally seen as punishing and uninviting and this can drive HIV-positive people out of care. Third, long-term engagement and adherence requires adaptation and incorporation of ART into daily life, a process which is facilitated by: inherent self-efficacy, social responsibilities, previous HIV-related illnesses and emotional, practical or financial support. These factors together can lead to a \"tipping point\", a point in time when patients choose to either engage or disengage from care. HIV-positive people may cycle in and out of these care states in response to fluctuations in influences over time. CONCLUSION This analysis provides a practical theory, arising from thematic synthesis of research, to help understand the dynamics of adherence to ART and engagement in HIV care. This can contribute to the design of service delivery approaches, and informed thinking and action on the part of policy makers, providers, and society: to understand what it is to be HIV-positive in Africa and how attitudes and the health service need to shift to help those with HIV lead 'normal' lives.", "qid": 34, "docid": "wdik9jcz", "rank": 93, "score": 8.047800064086914}, {"content": "Title: Acute Care Surgery during the COVID-19 pandemic in Spain: changes in volume, causes and complications. A multicentre retrospective cohort study Content: BACKGROUND: during the COVID-19 pandemic, the number of Acute Care Surgery procedures performed in Spanish hospitals decreased significantly. The aim of this study was to compare Acute Care Surgery activity during the COVID-19 pandemic and during a control period. MATERIAL AND METHODS: a multicenter retrospective cohort study was performed including patients who underwent Acute Care Surgery in three tertiary care hospitals in Spain during a control (11(th) March 2019 to 21(st) April 2019) and a pandemic (16(th) March 2020 to 26(th) April 2020) period. Type of surgical procedures, patients\u00b4 features and postoperative complications were compared. RESULTS: two hundred and eighty-five and 117 patients were included in each group. Mean number of patients who underwent Acute Care Surgery during the control and pandemic periods was 2.3 and 0.9 patients per day and hospital (p<0.001), representing a 58.9% decrease in Acute Care Surgery activity. Time from symptoms onset to patient arrival at the Emergency Department was longer during the pandemic (44.6 vs. 71.0 hours, p<0.001). Surgeries due to acute cholecystitis and complications from previous elective procedures decreased (26.7% vs. 9.4%) during the pandemic, while bowel obstructions and abdominal wall hernia surgeries increased (12.3% vs. 22.2%) (p=0.001). Morbidity was higher during pandemic period (34.7% vs. 47.1%, p=0.022), although this difference was not statistically significant in the multivariate analysis. Reoperation rate (17.9% vs. 12.8%, p=0.212) and mortality (6.7% vs. 4.3%, p=0.358) were similar in both groups. CONCLUSION: during the COVID-19 pandemic, a significant reduction in the performance of Acute Care Surgery procedures was observed. Moreso, a longer time from symptoms onset to patient arrival at the Emergency Department was noted. Higher morbidity was observed in patients undergoing Acute Care Surgery during the pandemic period, although there was not any difference in mortality or reoperation rate.", "qid": 34, "docid": "kacjdolq", "rank": 94, "score": 8.039400100708008}, {"content": "Title: Demographic and Clinical Characteristics of the Severe Covid-19 Infections: First Report from Mashhad University of Medical Sciences, Iran Content: Purpose. To report a comparison between fatalities and recovery of the severe Covid-19 infected patients based on demographic and clinical characteristics. Methods. Between 5 March and 12 May 2020, of 4,000 patients, 1,278 were laboratory confirmed to be Covid-19 infection in Mashhad, Iran. Finally, 334 deceased and 733 recovered cases were assessed in terms of demography, exposure history, health outcomes and clinical symptoms. Results. Mean (SD) age for confirmed patients, for deceased cases and for recovered cases. Mean (SD) age for all confirmed-patients was 56.9 (18.74), for the fatalities 67.26 (15.77) and for those recovered 52.82 (17.91) years. The rise of the mortality rate in relation to seniority was statistically significant. Despite a high frequency of Covid-19 infections accrued in the age groups of 30-39 and 40-49 years, most of these cases (88.2 and 85.8%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (9) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Fever (63.8%), cough (68.1%), and dyspnoea (72.7%) were the most frequent clinical symptoms. 5.2% of infected-cases were healthcare workers that two (3%) of them died. Most patients (48%) received both antiviral and antibiotic therapy. The mortality rate of Kaletra combination prescribed for severe cases was 46.7%. Conclusions. The characteristics of Covid-19 varied from died to survived infected patients. There were a higher number of fatalities in younger patients than in international studies. Diabetes and cardiovascular disorders were most prevalent co-morbidities. The study could not address the case-fatality rate of Covid-19 infection that remains for future studies.", "qid": 34, "docid": "460sr6iw", "rank": 95, "score": 8.037400245666504}, {"content": "Title: COVID-19 compassion in self-isolating old age: looking forward from family to regional and global concerns Content: Self-isolating with my wife, I feel gratitude and compassion for all those supporting us, particularly those who regularly deliver our food and our immediate family members who check on us frequently. My compassion goes out to those on the \u201cfrontline\u201d, particularly my niece and her daughter who are both nurses in a major hospital and who developed and recovered from COVID-19 symptoms. More broadly, I recognise that there are many communities that have had to cope with both geophysical and socio-politically created disasters while facing the COVID-19 pandemic, among then some young women bee-keepers in Uganda. In the UK context, I have great concern that severe funding cuts for regional and local public health services and disaster planning handicapped the country\u2019s response to coronavirus and may have been a factor in the UK\u2019s high coronavirus death rate. I see both positive and negative changes in air pollution and urban nature in our towns and cities, but also am concerned that we collectively may lose sight of the greater crises of climate change and species extinction. We have to work for a better future by taking forward the opportunities and lessons from our reactions to the pandemic. This leads to compassion for the yet unborn, our grandchildren\u2019s children, who might enter a less habitable, more unequal less collaborative world than the imperfect one we now enjoy.", "qid": 34, "docid": "c6muso58", "rank": 96, "score": 8.026300430297852}, {"content": "Title: A Letter to the Future AWWA Content: Dear Future AWWA Members, I'm writing to you on the 139th birthday of the American Water Works Association, and what a strange time it is We are in the midst of a global pandemic A disease called COVID\u201019 is spreading so quickly that we are running short on hospital beds and people are hoarding toilet paper At this moment, the United States has more confirmed cases than any other country and Canada is ranked 15th But I am not writing to tell you about the tragedy of COVID\u201019;I imagine the history books will capture that This is a letter about how today's water professionals are rising to the challenge through their selfless and often uncelebrated acts of courage They are building on the legacy of water professionals throughout AWWA's history, and I wish you were here to witness it As you\u2014the future AWWA\u2014look back on spring 2020, you will clearly see how access to safe, reliable water was critical in halting the spread of COVID\u201019 The simplest example I can provide is handwashing The practice of handwashing for at least 20 seconds, with plenty of soap, has never seemed so important Now, we are a society uniformly obsessed with washing our hands Because tap water is critical to personal hygiene and protecting the public's health, the US Environmental Protection Agency this week sent a letter to all governors, reminding them that water utility workers and water sector businesses that support water utilities should be considered \u201cessential\u201d as communities impose orders to keep people at home And in another sign of the essential nature of water service in a public health crisis, utilities are suspending water shutoffs and, in many cases, restoring service to customers who had previously been shut off But it isn't these policy decisions I hope you'll remember It's the exemplary\u2014and yes, courageous\u2014commitment of your predecessors in the water profession Each day, water professionals are delivering safe water to their communities and then cleaning the wastewater before returning it to the environment Never has this daily routine seemed more extraordinary These days, we are all being asked to participate in \u201csocial distancing,\u201d a term that most had never heard of before COVID\u201019 As schools and restaurants close and citizens are ordered to stay at home, your predecessors in the water profession continue to do what it takes to keep the water flowing, whether that is repairing mains, unclogging sewer lines (you can't imagine what some people do in the absence of toilet paper!), or ensuring treatment equipment is functioning properly Many water professionals are stationed 24/7 at treatment plants They are living apart from their own families so they can protect all of our families The ongoing pandemic has given our society new appreciation for the work of health professionals, police, and other first responders I would say that water professionals are not only first responders, but \u201ceveryday\u201d responders They are the super\u2010heroes we don't need to summon because they are already on the scene I am certain that in time we will be able to return to a more normal state, where a handshake is a handshake and not an elbow bump And when we do, I hope that we\u2014and the people who live in the communities we serve\u2014remember that water is critical to everything we care about and that it played a crucial role in eliminating COVID\u201019 It is not an overstatement to say that others\u2019 lives were in the hands of water professionals during the pandemic Poet and philosopher George Santayana is known for saying, \u201cThose who cannot remember the past are condemned to repeat it \u201d In this case, however, it would be wise to remember and repeat selfless acts like those of water professionals facing COVID\u201019 in the spring of 2020 In closing, Happy Birthday, AWWA, and my thanks to all who are members today and in the future Your commitment to the legacy of safe and reliable water service is, quite literally, life\u2010saving Sincerely, David B LaFrance Chief Executive Officer, American Water orks Association", "qid": 34, "docid": "sk86rbap", "rank": 97, "score": 8.005900382995605}, {"content": "Title: Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection. Content: OBJECTIVE To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.", "qid": 34, "docid": "mdesyj4m", "rank": 98, "score": 8.002599716186523}, {"content": "Title: Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection Content: OBJECTIVE: To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS: Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS: Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION: One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.", "qid": 34, "docid": "q0g65wyw", "rank": 99, "score": 8.002598762512207}, {"content": "Title: Short-term outcomes of laparoscopic versus open total gastrectomy: a matched-cohort study. Content: BACKGROUND This study was designed to compare short-term laparoscopic total gastrectomy (LTG) with open total gastrectomy (OTG) outcomes in gastric cancer. METHODS Seventy patients who underwent total gastrectomy via LTG or OTG were included. All cases were matched for stage, age, and sex by means of statistically generated selection of all gastrectomies performed during the same period. RESULTS Although the operation time was not longer for LTG, the time required for esophagojejunostomy was significantly longer in LTG than in OTG (43 vs 14 min, P < .05). The incidence of anastomotic complications was higher in the LTG group as well. CONCLUSIONS Postoperative complications such as anastomotic leakage and stenosis were observed more frequently in LTG. To improve the safety of esophagojejunostomy in LTG, technical innovations should be pursued.", "qid": 34, "docid": "sdsof4ua", "rank": 100, "score": 7.986499786376953}]}
{"query": "What new public datasets are available related to COVID-19?", "hits": [{"content": "Title: Does Non-COVID19 Lung Lesion Help? Investigating Transferability in COVID-19 CT Image Segmentation Content: Coronavirus disease 2019 (COVID-19) is a highly contagious virus spreading all around the world. Deep learning has been adopted as an effective technique to aid COVID-19 detection and segmentation from computed tomography (CT) images. The major challenge lies in the inadequate public COVID-19 datasets. Recently, transfer learning has become a widely used technique that leverages the knowledge gained while solving one problem and applying it to a different but related problem. However, it remains unclear whether various non-COVID19 lung lesions could contribute to segmenting COVID-19 infection areas and how to better conduct this transfer procedure. This paper provides a way to understand the transferability of non-COVID19 lung lesions. Based on a publicly available COVID-19 CT dataset and three public non-COVID19 datasets, we evaluate four transfer learning methods using 3D U-Net as a standard encoder-decoder method. The results reveal the benefits of transferring knowledge from non-COVID19 lung lesions, and learning from multiple lung lesion datasets can extract more general features, leading to accurate and robust pre-trained models. We further show the capability of the encoder to learn feature representations of lung lesions, which improves segmentation accuracy and facilitates training convergence. In addition, our proposed Multi-encoder learning method incorporates transferred lung lesion features from non-COVID19 datasets effectively and achieves significant improvement. These findings promote new insights into transfer learning for COVID-19 CT image segmentation, which can also be further generalized to other medical tasks.", "qid": 35, "docid": "h8k1jur8", "rank": 1, "score": 10.304499626159668}, {"content": "Title: Lest We Forget: A Dataset of Coronavirus-Related News Headlines in Swiss Media Content: We release our COVID-19 news dataset, containing more than 10,000 links to news articles related to the Coronavirus pandemic published in the Swiss media since early January 2020. This collection can prove beneficial in mining and analysis of the reaction of the Swiss media and the COVID-19 pandemic and extracting insightful information for further research. We hope this dataset helps researchers and the public deliver results that will help analyse the pandemic and potentially lead to a better understanding of the events.", "qid": 35, "docid": "fu373osb", "rank": 2, "score": 9.947199821472168}, {"content": "Title: CoAID: COVID-19 Healthcare Misinformation Dataset Content: As the COVID-19 virus quickly spreads around the world, unfortunately, misinformation related to COVID-19 also gets created and spreads like wild fire. Such misinformation has caused confusion among people, disruptions in society, and even deadly consequences in health problems. To be able to understand, detect, and mitigate such COVID-19 misinformation, therefore, has not only deep intellectual values but also huge societal impacts. To help researchers combat COVID-19 health misinformation, therefore, we present CoAID (Covid-19 heAlthcare mIsinformation Dataset), with diverse COVID-19 healthcare misinformation, including fake news on websites and social platforms, along with users' social engagement about such news. CoAID includes 1,896 news, 183,564 related user engagements, 516 social platform posts about COVID-19, and ground truth labels. The dataset is available at: https://github.com/cuilimeng/CoAID.", "qid": 35, "docid": "e2zz90sp", "rank": 3, "score": 9.894499778747559}, {"content": "Title: Public Opinions towards COVID-19 in California and New York on Twitter Content: Background: With the pandemic of COVID-19 and the release of related policies, discussions about the COVID-19 are widespread online. Social media becomes a reliable source for understanding public opinions toward this virus outbreak. Objective: This study aims to explore public opinions toward COVID-19 on social media by comparing the differences in sentiment changes and discussed topics between California and New York in the United States. Methods: A dataset with COVID-19-related Twitter posts was collected from March 5, 2020 to April 2, 2020 using Twitter streaming API. After removing any posts unrelated to COVID-19, as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from California state and the other from New York state. Sentiment analysis was conducted to obtain the sentiment score for each COVID-19 tweet. Topic modeling was applied to identify top topics related to COVID-19. Results: While the number of COVID-19 cases increased more rapidly in New York than in California in March 2020, the number of tweets posted has a similar trend over time in both states. COVID-19 tweets from California had more negative sentiment scores than New York. There were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of COVID-19 pandemic. The topic modeling results showed that the popular topics in both California and New York states are similar, with \"protective measures\" as the most prevalent topic associated with COVID-19 in both states. Conclusions: Twitter users from California had more negative sentiment scores towards COVID-19 than Twitter users from New York. The prevalent topics about COVID-19 discussed in both states were similar with some slight differences.", "qid": 35, "docid": "onipxf2z", "rank": 4, "score": 9.870499610900879}, {"content": "Title: Automatic Text Summarization of COVID-19 Medical Research Articles using BERT and GPT-2 Content: With the COVID-19 pandemic, there is a growing urgency for medical community to keep up with the accelerating growth in the new coronavirus-related literature. As a result, the COVID-19 Open Research Dataset Challenge has released a corpus of scholarly articles and is calling for machine learning approaches to help bridging the gap between the researchers and the rapidly growing publications. Here, we take advantage of the recent advances in pre-trained NLP models, BERT and OpenAI GPT-2, to solve this challenge by performing text summarization on this dataset. We evaluate the results using ROUGE scores and visual inspection. Our model provides abstractive and comprehensive information based on keywords extracted from the original articles. Our work can help the the medical community, by providing succinct summaries of articles for which the abstract are not already available.", "qid": 35, "docid": "6oiaf2cc", "rank": 5, "score": 9.851799964904785}, {"content": "Title: Unveiling COVID-19 from Chest X-ray with deep learning: a hurdles race with small data Content: The possibility to use widespread and simple chest X-ray (CXR) imaging for early screening of COVID-19 patients is attracting much interest from both the clinical and the AI community. In this study we provide insights and also raise warnings on what is reasonable to expect by applying deep-learning to COVID classification of CXR images. We provide a methodological guide and critical reading of an extensive set of statistical results that can be obtained using currently available datasets. In particular, we take the challenge posed by current small size COVID data and show how significant can be the bias introduced by transfer-learning using larger public non-COVID CXR datasets. We also contribute by providing results on a medium size COVID CXR dataset, just collected by one of the major emergency hospitals in Northern Italy during the peak of the COVID pandemic. These novel data allow us to contribute to validate the generalization capacity of preliminary results circulating in the scientific community. Our conclusions shed some light into the possibility to effectively discriminate COVID using CXR.", "qid": 35, "docid": "k31dagdy", "rank": 6, "score": 9.577500343322754}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next-generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present the Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2000 sequences per submission and the analysis of a new whole-genome sequence will take approximately 1 min. The tool has been tested and validated with hundreds of whole genomes from 10 coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY AND IMPLEMENTATION: https://www.genomedetective.com/app/typingtool/cov. CONTACT: koen@emweb.be or deoliveira@ukzn.ac.za. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "qid": 35, "docid": "88hswyln", "rank": 7, "score": 9.132100105285645}, {"content": "Title: Open access institutional and news media tweet dataset for COVID-19 social science research Content: As COVID-19 quickly became one of the most concerned global crisis, the demand for data in academic research is also increasing. Currently, there are several open access Twitter datasets, but none of them is dedicated to the institutional and news media Twitter data collection, to fill this blank, we retrieved data from 69 institutional/news media Twitter accounts, 17 of them were related to government and international organizations, 52 of them were news media across North America, Europe and Asia. We believe our open access data can provide researchers more availability to conduct social science research.", "qid": 35, "docid": "5o12mbut", "rank": 8, "score": 9.120100021362305}, {"content": "Title: POCOVID-Net: Automatic Detection of COVID-19 From a New Lung Ultrasound Imaging Dataset (POCUS) Content: With the rapid development of COVID-19 into a global pandemic, there is an ever more urgent need for cheap, fast and reliable tools that can assist physicians in diagnosing COVID-19. Medical imaging such as CT can take a key role in complementing conventional diagnostic tools from molecular biology, and, using deep learning techniques, several automatic systems were demonstrated promising performances using CT or X-ray data. Here, we advocate a more prominent role of point-of-care ultrasound imaging to guide COVID-19 detection. Ultrasound is non-invasive and ubiquitous in medical facilities around the globe. Our contribution is threefold. First, we gather a lung ultrasound (POCUS) dataset consisting of (currently) 1103 images (654 COVID-19, 277 bacterial pneumonia and 172 healthy controls), sampled from 64 videos. While this dataset was assembled from various online sources and is by no means exhaustive, it was processed specifically to feed deep learning models and is intended to serve as a starting point for an open-access initiative. Second, we train a deep convolutional neural network (POCOVID-Net) on this 3-class dataset and achieve an accuracy of 89% and, by a majority vote, a video accuracy of 92% . For detecting COVID-19 in particular, the model performs with a sensitivity of 0.96, a specificity of 0.79 and F1-score of 0.92 in a 5-fold cross validation. Third, we provide an open-access web service (POCOVIDScreen) that is available at: https://pocovidscreen.org. The website deploys the predictive model, allowing to perform predictions on ultrasound lung images. In addition, it grants medical staff the option to (bulk) upload their own screenings in order to contribute to the growing public database of pathological lung ultrasound images. Dataset and code are available from: https://github.com/jannisborn/covid19_pocus_ultrasound", "qid": 35, "docid": "vw6kpuz4", "rank": 9, "score": 9.116499900817871}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov SUPPLEMENTARY INFORMATION:", "qid": 35, "docid": "st5idleq", "rank": 10, "score": 9.102499961853027}, {"content": "Title: Recognizing flu-like symptoms from videos Content: BACKGROUND: Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. RESULTS: In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. CONCLUSIONS: Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.", "qid": 35, "docid": "gm1e9j80", "rank": 11, "score": 8.969599723815918}, {"content": "Title: Statistical Explorations and Univariate Timeseries Analysis on COVID-19 Datasets to Understand the Trend of Disease Spreading and Death Content: \"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)\", the novel coronavirus, is responsible for the ongoing worldwide pandemic. \"World Health Organization (WHO)\" assigned an \"International Classification of Diseases (ICD)\" code-\"COVID-19\"-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with \"Middle East Respiratory Syndrome (MERS-CoV)\", \"Severe Acute Respiratory Syndrome (SARS-CoV)\", and now with this new virus, namely \"SARS-CoV-2\", or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a \"spread factor (f)\", and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in \"ourworldindata.org (Oxford University database)\", and newly simulated datasets, following the analysis of different univariate \"Long Short Term Memory (LSTM)\" models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months - January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.", "qid": 35, "docid": "30ri8v61", "rank": 12, "score": 8.962200164794922}, {"content": "Title: Statistical Explorations and Univariate Timeseries Analysis on COVID-19 Datasets to Understand the Trend of Disease Spreading and Death Content: \u201cSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)\u201d, the novel coronavirus, is responsible for the ongoing worldwide pandemic. \u201cWorld Health Organization (WHO)\u201d assigned an \u201cInternational Classification of Diseases (ICD)\u201d code\u2014\u201cCOVID-19\u201d-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with \u201cMiddle East Respiratory Syndrome (MERS-CoV)\u201d, \u201cSevere Acute Respiratory Syndrome (SARS-CoV)\u201d, and now with this new virus, namely \u201cSARS-CoV-2\u201d, or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a \u201cspread factor (f)\u201d, and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in \u201courworldindata.org (Oxford University database)\u201d, and newly simulated datasets, following the analysis of different univariate \u201cLong Short Term Memory (LSTM)\u201d models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months\u2014January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.", "qid": 35, "docid": "5ll60v8p", "rank": 13, "score": 8.962199211120605}, {"content": "Title: A First Instagram Dataset on COVID-19 Content: The novel coronavirus (COVID-19) pandemic outbreak is drastically shaping and reshaping many aspects of our life, with a huge impact on our social life. In this era of lockdown policies in most of the major cities around the world, we see a huge increase in people and professional engagement in social media. Social media is playing an important role in news propagation as well as keeping people in contact. At the same time, this source is both a blessing and a curse as the coronavirus infodemic has become a major concern, and is already a topic that needs special attention and further research. In this paper, we provide a multilingual coronavirus (COVID-19) Instagram dataset that we have been continuously collected since March 30, 2020. We are making our dataset available to the research community at Github. We believe that this contribution will help the community to better understand the dynamics behind this phenomenon in Instagram, as one of the major social media. This dataset could also help study the propagation of misinformation related to this outbreak.", "qid": 35, "docid": "lqhainz3", "rank": 14, "score": 8.916000366210938}, {"content": "Title: Computational analysis of the SARS-CoV-2 and other viruses based on the Kolmogorov\u2019s complexity and Shannon\u2019s information theories Content: This paper tackles the information of 133 RNA viruses available in public databases under the light of several mathematical and computational tools. First, the formal concepts of distance metrics, Kolmogorov complexity and Shannon information are recalled. Second, the computational tools available presently for tackling and visualizing patterns embedded in datasets, such as the hierarchical clustering and the multidimensional scaling, are discussed. The synergies of the common application of the mathematical and computational resources are then used for exploring the RNA data, cross-evaluating the normalized compression distance, entropy and Jensen\u2013Shannon divergence, versus representations in two and three dimensions. The results of these different perspectives give extra light in what concerns the relations between the distinct RNA viruses.", "qid": 35, "docid": "psh5jevz", "rank": 15, "score": 8.908699989318848}, {"content": "Title: Rapidly Bootstrapping a Question Answering Dataset for COVID-19 Content: We present CovidQA, the beginnings of a question answering dataset specifically designed for COVID-19, built by hand from knowledge gathered from Kaggle's COVID-19 Open Research Dataset Challenge. To our knowledge, this is the first publicly available resource of its type, and intended as a stopgap measure for guiding research until more substantial evaluation resources become available. While this dataset, comprising 124 question-article pairs as of the present version 0.1 release, does not have sufficient examples for supervised machine learning, we believe that it can be helpful for evaluating the zero-shot or transfer capabilities of existing models on topics specifically related to COVID-19. This paper describes our methodology for constructing the dataset and presents the effectiveness of a number of baselines, including term-based techniques and various transformer-based models. The dataset is available at http://covidqa.ai/", "qid": 35, "docid": "vaeyoxv7", "rank": 16, "score": 8.871299743652344}, {"content": "Title: Automated Chest CT Image Segmentation of COVID-19 Lung Infection based on 3D U-Net Content: The coronavirus disease 2019 (COVID-19) affects billions of lives around the world and has a significant impact on public healthcare. Due to rising skepticism towards the sensitivity of RT-PCR as screening method, medical imaging like computed tomography offers great potential as alternative. For this reason, automated image segmentation is highly desired as clinical decision support for quantitative assessment and disease monitoring. However, publicly available COVID-19 imaging data is limited which leads to overfitting of traditional approaches. To address this problem, we propose an innovative automated segmentation pipeline for COVID-19 infected regions, which is able to handle small datasets by utilization as variant databases. Our method focuses on on-the-fly generation of unique and random image patches for training by performing several preprocessing methods and exploiting extensive data augmentation. For further reduction of the overfitting risk, we implemented a standard 3D U-Net architecture instead of new or computational complex neural network architectures. Through a 5-fold cross-validation on 20 CT scans of COVID-19 patients, we were able to develop a highly accurate as well as robust segmentation model for lungs and COVID-19 infected regions without overfitting on the limited data. Our method achieved Dice similarity coefficients of 0.956 for lungs and 0.761 for infection. We demonstrated that the proposed method outperforms related approaches, advances the state-of-the-art for COVID-19 segmentation and improves medical image analysis with limited data. The code and model are available under the following link: https://github.com/frankkramer-lab/covid19.MIScnn", "qid": 35, "docid": "xh1s6x4n", "rank": 17, "score": 8.861800193786621}, {"content": "Title: A curated transcriptome dataset collection to investigate the blood transcriptional response to viral respiratory tract infection and vaccination. Content: The human immune defense mechanisms and factors associated with good versus poor health outcomes following viral respiratory tract infections (VRTI), as well as correlates of protection following vaccination against respiratory viruses, remain incompletely understood. To shed further light into these mechanisms, a number of systems-scale studies have been conducted to measure transcriptional changes in blood leukocytes of either naturally or experimentally infected individuals, or in individual\u2019s post-vaccination. Here we are making available a public repository, for research investigators for interpretation, a collection of transcriptome datasets obtained from human whole blood and peripheral blood mononuclear cells (PBMC) to investigate the transcriptional responses following viral respiratory tract infection or vaccination against respiratory viruses. In total, Thirty one31 datasets, associated to viral respiratory tract infections and their related vaccination studies, were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom web application designed for interactive query and visualization of integrated large-scale data. Quality control checks, using relevant biological markers, were performed. Multiple sample groupings and rank lists were created to facilitate dataset query and interpretation. Via this interface, users can generate web links to customized graphical views, which may be subsequently inserted into manuscripts to report novel findings. The GXB tool enables browsing of a single gene across projects, providing new perspectives on the role of a given molecule across biological systems in the diagnostic and prognostic following VRTI but also in identifying new correlates of protection. This dataset collection is available at: http://vri1.gxbsidra.org/dm3/geneBrowser/list.", "qid": 35, "docid": "xsmn1osi", "rank": 18, "score": 8.810500144958496}, {"content": "Title: Visualising COVID-19 Research Content: The world has seen in 2020 an unprecedented global outbreak of SARS-CoV-2, a new strain of coronavirus, causing the COVID-19 pandemic, and radically changing our lives and work conditions. Many scientists are working tirelessly to find a treatment and a possible vaccine. Furthermore, governments, scientific institutions and companies are acting quickly to make resources available, including funds and the opening of large-volume data repositories, to accelerate innovation and discovery aimed at solving this pandemic. In this paper, we develop a novel automated theme-based visualisation method, combining advanced data modelling of large corpora, information mapping and trend analysis, to provide a top-down and bottom-up browsing and search interface for quick discovery of topics and research resources. We apply this method on two recently released publications datasets (Dimensions' COVID-19 dataset and the Allen Institute for AI's CORD-19). The results reveal intriguing information including increased efforts in topics such as social distancing; cross-domain initiatives (e.g. mental health and education); evolving research in medical topics; and the unfolding trajectory of the virus in different territories through publications. The results also demonstrate the need to quickly and automatically enable search and browsing of large corpora. We believe our methodology will improve future large volume visualisation and discovery systems but also hope our visualisation interfaces will currently aid scientists, researchers, and the general public to tackle the numerous issues in the fight against the COVID-19 pandemic.", "qid": 35, "docid": "hn37wkhf", "rank": 19, "score": 8.809700012207031}, {"content": "Title: Covid-19: automatic detection from X-ray images utilizing transfer learning with convolutional neural networks Content: In this study, a dataset of X-ray images from patients with common bacterial pneumonia, confirmed Covid-19 disease, and normal incidents, was utilized for the automatic detection of the Coronavirus disease. The aim of the study is to evaluate the performance of state-of-the-art convolutional neural network architectures proposed over the recent years for medical image classification. Specifically, the procedure called Transfer Learning was adopted. With transfer learning, the detection of various abnormalities in small medical image datasets is an achievable target, often yielding remarkable results. The datasets utilized in this experiment are two. Firstly, a collection of 1427 X-ray images including 224 images with confirmed Covid-19 disease, 700 images with confirmed common bacterial pneumonia, and 504 images of normal conditions. Secondly, a dataset including 224 images with confirmed Covid-19 disease, 714 images with confirmed bacterial and viral pneumonia, and 504 images of normal conditions. The data was collected from the available X-ray images on public medical repositories. The results suggest that Deep Learning with X-ray imaging may extract significant biomarkers related to the Covid-19 disease, while the best accuracy, sensitivity, and specificity obtained is 96.78%, 98.66%, and 96.46% respectively. Since by now, all diagnostic tests show failure rates such as to raise concerns, the probability of incorporating X-rays into the diagnosis of the disease could be assessed by the medical community, based on the findings, while more research to evaluate the X-ray approach from different aspects may be conducted.", "qid": 35, "docid": "x4clpzte", "rank": 20, "score": 8.782600402832031}, {"content": "Title: CoronaVis: A Real-time COVID-19 Tweets Data Analyzer and Data Repository Content: Due to the nature of the data and public interaction, twitter is becoming more and more useful to understand and model various events. The goal of CoronaVis is to use tweets as the information shared by the people to visualize topic modeling, study subjectivity, and to model the human emotions during the COVID-19 pandemic. The main objective is to explore the psychology and behavior of the societies at large which can assist in managing the economic and social crisis during the ongoing pandemic as well as the after-effects of it. The novel coronavirus (COVID-19) pandemic forced people to stay at home to reduce the spread of the virus by maintaining social distancing. However, social media is keeping people connected both locally and globally. People are sharing information (e.g. personal opinions, some facts, news, status, etc.) on social media platforms which can be helpful to understand the various public behavior such as emotions, sentiments, and mobility during the ongoing pandemic. In this work, we develop a live application to observe the tweets on COVID-19 generated from the USA. In this paper, we have generated various data analytics over a period of time to study the changes in topics, subjectivity, and human emotions. We also share a cleaned and processed dataset named CoronaVis Twitter dataset (focused on the United States) available to the research community at https://github.com/mykabir/COVID19. This will enable the community to find more useful insights and create different applications and models to fight with COVID-19 pandemic and future pandemics as well.", "qid": 35, "docid": "iajw2s5w", "rank": 21, "score": 8.635100364685059}, {"content": "Title: On the Generation of Medical Dialogues for COVID-19 Content: Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets - CovidDialog - (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog datasets. Experiments demonstrate that these approaches are promising in generating meaningful medical dialogue about COVID-19. But more advanced approaches are needed to build a fully useful dialogue system that can offer accurate COVID-related consultations. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue", "qid": 35, "docid": "tprgbl51", "rank": 22, "score": 8.529500007629395}, {"content": "Title: NAIST COVID: Multilingual COVID-19 Twitter and Weibo Dataset Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, it has affected over 200 countries and billions of people worldwide. This has affected the social life of people owing to enforcements, such as\"social distancing\"and\"stay at home.\"This has resulted in an increasing interaction through social media. Given that social media can bring us valuable information about COVID-19 at a global scale, it is important to share the data and encourage social media studies against COVID-19 or other infectious diseases. Therefore, we have released a multilingual dataset of social media posts related to COVID-19, consisting of microblogs in English and Japanese from Twitter and those in Chinese from Weibo. The data cover microblogs from January 20, 2020, to March 24, 2020. This paper also provides a quantitative as well as qualitative analysis of these datasets by creating daily word clouds as an example of text-mining analysis. The dataset is now available on Github. This dataset can be analyzed in a multitude of ways and is expected to help in efficient communication of precautions related to COVID-19.", "qid": 35, "docid": "o8b1rtux", "rank": 23, "score": 8.51729965209961}, {"content": "Title: Coronaviruses and people with intellectual disability: an exploratory data analysis Content: BACKGROUND: Corona virus disease 2019 (COVID\u201019) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID\u201019. Recently, the COVID\u201019 Open Research Dataset (CORD\u201019) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD\u201019, we identified full\u2010text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency\u2013inverse document frequency analysis in combination with K\u2010means clustering. RESULTS: Two hundred fifty\u2010nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD\u201019 open research dataset consists of valuable information about not only COVID\u201019 disease but also ID and the relationship between them. We suggest researchers investigate literature\u2010based discovery approaches on the CORD\u201019 and develop a new dataset that addresses the intersection of these two fields for further research.", "qid": 35, "docid": "pksis5da", "rank": 24, "score": 8.492899894714355}, {"content": "Title: Coronaviruses and people with intellectual disability: an exploratory data analysis Content: BACKGROUND: Corona virus disease 2019 (COVID-19) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID-19. Recently, the COVID-19 Open Research Dataset (CORD-19) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD-19, we identified full-text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency-inverse document frequency analysis in combination with K-means clustering. RESULTS: Two hundred fifty-nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD-19 open research dataset consists of valuable information about not only COVID-19 disease but also ID and the relationship between them. We suggest researchers investigate literature-based discovery approaches on the CORD-19 and develop a new dataset that addresses the intersection of these two fields for further research.", "qid": 35, "docid": "sg8epmf0", "rank": 25, "score": 8.492898941040039}, {"content": "Title: Integrated Time Series Summarization and Prediction Algorithm and its Application to COVID-19 Data Mining Content: This paper proposes a simple method to extract from a set of multiple related time series a compressed representation for each time series based on statistics for the entire set of all time series. This is achieved by a hierarchical algorithm that first generates an alphabet of shapelets based on the segmentation of centroids for clustered data, before labels of these shapelets are assigned to the segmentation of each single time series via nearest neighbor search using unconstrained dynamic time warping as distance measure to deal with non-uniform time series lenghts. Thereby, a sequence of labels is assigned for each time series. Completion of the last label sequence permits prediction of individual time series. Proposed method is evaluated on two global COVID-19 datasets, first, for the number of daily net cases (daily new infections minus daily recoveries), and, second, for the number of daily deaths attributed to COVID-19 as of April 27, 2020. The first dataset involves 249 time series for different countries, each of length 96. The second dataset involves 264 time series, each of length 96. Based on detected anomalies in available data a decentralized exit strategy from lockdowns is advocated.", "qid": 35, "docid": "s8flrw7q", "rank": 26, "score": 8.480299949645996}, {"content": "Title: Deep Learning for Screening COVID-19 using Chest X-Ray Images Content: With the ever increasing demand for screening millions of prospective\"novel coronavirus\"or COVID-19 cases, and due to the emergence of high false negatives in the commonly used PCR tests, the necessity for probing an alternative simple screening mechanism of COVID-19 using radiological images (like chest X-Rays) assumes importance. In this scenario, machine learning (ML) and deep learning (DL) offer fast, automated, effective strategies to detect abnormalities and extract key features of the altered lung parenchyma, which may be related to specific signatures of the COVID-19 virus. However, the available COVID-19 datasets are inadequate to train deep neural networks. Therefore, we propose a new concept called domain extension transfer learning (DETL). We employ DETL, with pre-trained deep convolutional neural network, on a related large chest X-Ray dataset that is tuned for classifying between four classes viz. $normal$, $other\\_disease$, $pneumonia$ and $Covid-19$. A 5-fold cross validation is performed to estimate the feasibility of using chest X-Rays to diagnose COVID-19. The initial results show promise, with the possibility of replication on bigger and more diverse data sets. The overall accuracy was measured as $95.3\\% \\pm 0.02$. In order to get an idea about the COVID-19 detection transparency, we employed the concept of Gradient Class Activation Map (Grad-CAM) for detecting the regions where the model paid more attention during the classification. This was found to strongly correlate with clinical findings, as validated by experts.", "qid": 35, "docid": "drgay9n0", "rank": 27, "score": 8.425399780273438}, {"content": "Title: Deep Learning for Screening COVID-19 using Chest X-Ray Images Content: With the ever increasing demand for screening millions of prospective \"novel coronavirus\" or COVID-19 cases, and due to the emergence of high false negatives in the commonly used PCR tests, the necessity for probing an alternative simple screening mechanism of COVID-19 using radiological images (like chest X-Rays) assumes importance. In this scenario, machine learning (ML) and deep learning (DL) offer fast, automated, effective strategies to detect abnormalities and extract key features of the altered lung parenchyma, which may be related to specific signatures of the COVID-19 virus. However, the available COVID-19 datasets are inadequate to train deep neural networks. Therefore, we propose a new concept called domain extension transfer learning (DETL). We employ DETL, with pre-trained deep convolutional neural network, on a related large chest X-Ray dataset that is tuned for classifying between four classes viz, normal, other_disease, pneumonia and Covid-19. A 5-fold cross validation is performed to estimate the feasibility of using chest X-Rays to diagnose COVID-19. The initial results show promise, with the possibility of replication on bigger and more diverse data sets. The overall accuracy was measured as 95.3%{+/-}0.02. In order to get an idea about the COVID-19 detection transparency, we employed the concept of Gradient Class Activation Map (Grad-CAM) for detecting the regions where the model paid more attention during the classification. This was found to strongly correlate with clinical findings, as validated by experts.", "qid": 35, "docid": "e941jx5c", "rank": 28, "score": 8.425398826599121}, {"content": "Title: FakeCovid -- A Multilingual Cross-domain Fact Check News Dataset for COVID-19 Content: In this paper, we present a first multilingual cross-domain dataset of 5182 fact-checked news articles for COVID-19, collected from 04/01/2020 to 15/05/2020. We have collected the fact-checked articles from 92 different fact-checking websites after obtaining references from Poynter and Snopes. We have manually annotated articles into 11 different categories of the fact-checked news according to their content. The dataset is in 40 languages from 105 countries. We have built a classifier to detect fake news and present results for the automatic fake news detection and its class. Our model achieves an F1 score of 0.76 to detect the false class and other fact check articles. The FakeCovid dataset is available at Github.", "qid": 35, "docid": "9it9pgq1", "rank": 29, "score": 8.410400390625}, {"content": "Title: Unique transcriptional changes in coagulation cascade genes in SARS-CoV-2-infected lung epithelial cells: A potential factor in COVID-19 coagulopathies Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. While there are many theories for the cause of this pathology, including hyper inflammation and excess tissue damage, the cellular and molecular underpinnings are not yet clear. By analyzing transcriptomic data sets from experimental and clinical research teams, we determined that changes in the gene expression of genes important in the extrinsic coagulation cascade in the lung epithelium may be important triggers for COVID-19 coagulopathy. This regulation of the extrinsic blood coagulation cascade is not seen with influenza A virus (IAV)-infected NHBEs suggesting that the lung epithelial derived coagulopathies are specific to SARS-Cov-2 infection. This study is the first to identify potential lung epithelial cell derived factors contributing to COVID-19 associated coagulopathy. GRAPHICAL ABSTRACT AUTHOR SUMMARY Why was this study done? Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. Understanding the molecular basis of dysregulated blood coagulation during SARS-CoV-2 infection may help promote new therapeutic strategies to mitigate these complications in COVID-19 patients. What did the researchers do and find? We analyzed three publicly available RNA sequencing datasets to identify possible molecular etiologies of COVID-19 associated coagulopathies. These data sets include sequencing libraries from clinically isolated samples of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) from SARS-CoV-2 positive patients and healthy controls. We also analyzed a publicly available RNA sequencing dataset derived from in vitro SARS-CoV-2 infected primary normal human bronchial epithelial (NHBE) cells and mock infected samples. Pathway analysis of both NHBE and BALF differential gene expression gene sets. We found that SARS-CoV-2 infection induces the activation of the extrinsic blood coagulation cascade and suppression of the plasminogen activation system in both NHBEs and cells isolated from the BALF. PBMCs did not differentially express genes regulating blood coagulation. Comparison with influenza A virus (IAV)-infected NHBEs revealed that the regulation of the extrinsic blood coagulation cascade is unique to SARS-CoV-2, and not seen with IAV infection. What do these findings mean? The hyper-activation of the extrinsic blood coagulation cascade and the suppression of the plasminogen activation system in SARS-CoV-2 infected epithelial cells may drive diverse coagulopathies in the lung and distal organ systems. The gene transcription pattern in SARS-CoV-2 infected epithelial cells is distinct from IAV infected epithelial cells with regards to the regulation of blood coagulation.", "qid": 35, "docid": "ckvsn0ah", "rank": 30, "score": 8.399499893188477}, {"content": "Title: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Content: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining", "qid": 35, "docid": "3wuh6k6g", "rank": 31, "score": 8.382200241088867}, {"content": "Title: Collective response to the media coverage of COVID-19 Pandemic on Reddit and Wikipedia Content: The exposure and consumption of information during epidemic outbreaks may alter risk perception, trigger behavioural changes, and ultimately affect the evolution of the disease. It is thus of the uttermost importance to map information dissemination by mainstream media outlets and public response. However, our understanding of this exposure-response dynamic during COVID-19 pandemic is still limited. In this paper, we provide a characterization of media coverage and online collective attention to COVID-19 pandemic in four countries: Italy, United Kingdom, United States, and Canada. For this purpose, we collect an heterogeneous dataset including 227,768 online news articles and 13,448 Youtube videos published by mainstream media, 107,898 users posts and 3,829,309 comments on the social media platform Reddit, and 278,456,892 views to COVID-19 related Wikipedia pages. Our results show that public attention, quantified as users activity on Reddit and active searches on Wikipedia pages, is mainly driven by media coverage and declines rapidly, while news exposure and COVID-19 incidence remain high. Furthermore, by using an unsupervised, dynamical topic modeling approach, we show that while the attention dedicated to different topics by media and online users are in good accordance, interesting deviations emerge in their temporal patterns. Overall, our findings offer an additional key to interpret public perception/response to the current global health emergency and raise questions about the effects of attention saturation on collective awareness, risk perception and thus on tendencies towards behavioural changes.", "qid": 35, "docid": "ajw4j8b8", "rank": 32, "score": 8.29419994354248}, {"content": "Title: Policy response, social media and science journalism for the sustainability of the public health system amid the COVID-19 outbreak: The vietnam lessons Content: Having geographical proximity and a high volume of trade with China, the first country to record an outbreak of the new Coronavirus disease (COVID-19), Vietnam was expected to have a high risk of transmission. However, as of 4 April 2020, in comparison to attempts to containing the disease around the world, responses from Vietnam are seen as prompt and effective in protecting the interests of its citizens, with 239 confirmed cases and no fatalities. This study analyzes the situation in terms of Vietnam's policy response, social media and science journalism. A self-made web crawl engine was used to scan and collect official media news related to COVID-19 between the beginning of January and April 4, yielding a comprehensive dataset of 14,952 news items. The findings shed light on how Vietnam-despite being under-resourced-has demonstrated political readiness to combat the emerging pandemic since the earliest days. Timely communication on any developments of the outbreak from the government and the media, combined with up-to-date research on the new virus by the Vietnamese science community, have altogether provided reliable sources of information. By emphasizing the need for immediate and genuine cooperation between government, civil society and private individuals, the case study offers valuable lessons for other nations concerning not only the concurrent fight against the COVID-19 pandemic but also the overall responses to a public health crisis.", "qid": 35, "docid": "t6sfs24q", "rank": 33, "score": 8.287699699401855}, {"content": "Title: CO-Search: COVID-19 Information Retrieval with Semantic Search, Question Answering, and Abstractive Summarization Content: The COVID-19 global pandemic has resulted in international efforts to understand, track, and mitigate the disease, yielding a significant corpus of COVID-19 and SARS-CoV-2-related publications across scientific disciplines. As of May 2020, 128,000 coronavirus-related publications have been collected through the COVID-19 Open Research Dataset Challenge. Here we present CO-Search, a retriever-ranker semantic search engine designed to handle complex queries over the COVID-19 literature, potentially aiding overburdened health workers in finding scientific answers during a time of crisis. The retriever is built from a Siamese-BERT encoder that is linearly composed with a TF-IDF vectorizer, and reciprocal-rank fused with a BM25 vectorizer. The ranker is composed of a multi-hop question-answering module, that together with a multi-paragraph abstractive summarizer adjust retriever scores. To account for the domain-specific and relatively limited dataset, we generate a bipartite graph of document paragraphs and citations, creating 1.3 million (citation title, paragraph) tuples for training the encoder. We evaluate our system on the data of the TREC-COVID information retrieval challenge. CO-Search obtains top performance on the datasets of the first and second rounds, across several key metrics: normalized discounted cumulative gain, precision, mean average precision, and binary preference.", "qid": 35, "docid": "qfeo6sch", "rank": 34, "score": 8.286999702453613}, {"content": "Title: Advertisers Jump on Coronavirus Bandwagon: Politics, News, and Business Content: In the age of social media, disasters and epidemics usher not only a devastation and affliction in the physical world, but also prompt a deluge of information, opinions, prognoses and advice to billions of internet users. The coronavirus epidemic of 2019-2020, or COVID-19, is no exception, with the World Health Organization warning of a possible\"infodemic\"of fake news. In this study, we examine the alternative narratives around the coronavirus outbreak through advertisements promoted on Facebook, the largest social media platform in the US. Using the new Facebook Ads Library, we discover advertisers from public health and non-profit sectors, alongside those from news media, politics, and business, incorporating coronavirus into their messaging and agenda. We find the virus used in political attacks, donation solicitations, business promotion, stock market advice, and animal rights campaigning. Among these, we find several instances of possible misinformation, ranging from bioweapons conspiracy theories to unverifiable claims by politicians. As we make the dataset available to the community, we hope the advertising domain will become an important part of quality control for public health communication and public discourse in general.", "qid": 35, "docid": "8l0mpv3g", "rank": 35, "score": 8.274900436401367}, {"content": "Title: Identification of spatial variations in COVID-19 epidemiological data using K-Means clustering algorithm: a global perspective Content: Background: Discerning spatial variations of COVID-19 through quantitative analysis operating on the geographically designated datasets relating to socio-demographics and epidemiological data facilitate strategy planning in curtailing the transmission of the disease and focus on articulation of necessary interventions in an informed manner. Methods: K-means clustering was employed on the available country-specific COVID-19 epidemiological data and the influential background characteristics. Country-specific case fatality rates and the average number of people tested positive for COVID-19 per every 10,000 population in each country were derived from the WHO COVID-19 situation report 107, and were used for clustering along with the background characteristics of proportion of countrys population aged >65 years and percentage GDP spent as public health expenditure. Results: The algorithm grouped the 89 countries into cluster 1 and Cluster 2 of sizes 54 and 35, respectively. It is apparent that Americas, European countries, and Australia formed a major part of cluster 2 with high COVID-19 case fatality rate, higher proportion of countrys population tested COVID-19 positive, higher percentage of GDP spent as public health expenditure, and greater percentage of population being more than 65 years of age. Conclusion: In spite of the positive correlation between high public health expenditure (%GDP) and COVID-19 incidence, case fatality rate, the immediate task ahead of most of the low and middle income countries is to strengthen their public health systems realizing that the correlation found in this study could be spurious in light of the underreported number of cases and poor death registration.", "qid": 35, "docid": "2kiyzq4b", "rank": 36, "score": 8.266300201416016}, {"content": "Title: Comprehensive Named Entity Recognition on CORD-19 with Distant or Weak Supervision Content: We created this CORD-NER dataset with comprehensive named entity recognition (NER) on the COVID-19 Open Research Dataset Challenge (CORD-19) corpus (2020-03-13). This CORD-NER dataset covers 75 fine-grained entity types: In addition to the common biomedical entity types (e.g., genes, chemicals and diseases), it covers many new entity types related explicitly to the COVID-19 studies (e.g., coronaviruses, viral proteins, evolution, materials, substrates and immune responses), which may benefit research on COVID-19 related virus, spreading mechanisms, and potential vaccines. CORD-NER annotation is a combination of four sources with different NER methods. The quality of CORD-NER annotation surpasses SciSpacy (over 10% higher on the F1 score based on a sample set of documents), a fully supervised BioNER tool. Moreover, CORD-NER supports incrementally adding new documents as well as adding new entity types when needed by adding dozens of seeds as the input examples. We will constantly update CORD-NER based on the incremental updates of the CORD-19 corpus and the improvement of our system.", "qid": 35, "docid": "2l42genc", "rank": 37, "score": 8.265299797058105}, {"content": "Title: Artificial Intelligence and COVID-19: A Multidisciplinary Approach Content: The COVID-19 pandemic is taking a colossal toll in human suffering and lives. A significant amount of new scientific research and data sharing is underway due to the pandemic which is still rapidly spreading. There is now a growing amount of coronavirus related datasets as well as published papers that must be leveraged along with artificial intelligence (AI) to fight this pandemic by driving news approaches to drug discovery, vaccine development, and public awareness. AI can be used to mine this avalanche of new data and papers to extract new insights by cross-referencing papers and searching for patterns that AI algorithms could help discover new possible treatments or help in vaccine development. Drug discovery is not a trivial task and AI technologies like deep learning can help accelerate this process by helping predict which existing drugs, or brand-new drug-like molecules could treat COVID-19. AI techniques can also help disseminate vital information across the globe and reduce the spread of false information about COVID-19. The positive power and potential of AI must be harnessed in the fight to slow the spread of COVID-19 in order to save lives and limit the economic havoc due to this horrific disease.", "qid": 35, "docid": "9xgrthg7", "rank": 38, "score": 8.26449966430664}, {"content": "Title: Frequency of testing for COVID 19 infection and the presence of higher number of available beds per country predict outcomes with the infection, not the GDP of the country - A descriptive statistical analysis Content: Introduction: The novel coronavirus epidemic which originated in late 2019 from China has wreaked havoc on millions across the world with illness, death and socioeconomic recession. As of now no valid treatment or preventative strategy has evolved worldwide and governments across the world have been forced to take the draconian step of social isolation in communities by enforcing lockdowns. Aim of this Study: This study aims to correlate the rates of infection with the novel coronavirus and total deaths as the primary output variable. In addition the strength of association between infection rates and total death in comparison to GDP share of the respective countries, physicians, hospital beds and rates of testing for COVID 19 infection per thousand patients, is being assessed, in a bid to develop a model which would help to develop tools to reduce the impact of this disease. Material & Methods Data relating to number of cases, severity, cases recovered and deaths worldwide and specifically for the top six countries affected was collected from the WHO COVID-19 situation report which is being updated on a daily basis till 22nd March 2020, the date of analysis. Additional data related to GDP, physician and hospital bed per 1000 patients were procured from the World Bank database. All data were collected in a file in CSV format. Analysis was conducted in Jupyter notebook with Python 3.8.2 software and also with XL-Stat statistical software for excel. The analytical strategy was descriptive with no inferential overtones. Results: COVID 19 infection strongly correlates with total deaths (r : 0.89), with a predicted death rate of 25 patients per 1000 affected. There was no correlation between the GDP growth of the country and number of treating physicians/1000 patient population with any COVID 19 related outcome. However there was a negative correlation between COVID 19-related deaths and the number of beds available per 1000 population [r=-0.34]. Importantly there is an inverse correlation between the number of tests conducted per million population with the rates of active infections [r=-0.12] , new cases [r=-0.38] and new deaths [r=-0.28] in COVID 19. Conclusion: This is the first study to assess parameters other than age and sex and sets out a robust dataset which indicates an increased risk of worsening outcomes with lesser number of beds and testing, suggesting that the need of the hour is to increase available bed numbers and to increase rates of testing.", "qid": 35, "docid": "4707pec6", "rank": 39, "score": 8.24489974975586}, {"content": "Title: A critical analysis of corona related data: What the more reliable data can imply for Western-Europe Content: We present a less common type of discussion about COVID-19 data, beginning with the observation that the number of people reported deceased following COVID-19 infection is currently the most reliable dataset to be used. When the available real-life data are visualized for a number of European countries, they reveal the commonly seen exponential increase, though with different absolute rates, and over time different periods. More interesting information is obtained upon inspection of the daily increments in deaths. These curves look very similar to those for China, and seem to indicate that in European countries that have imposed more strict human-human contact measures, in particular Italy and Spain, where we have seen a decrease in daily deaths since early April, it is to be expected it will take 40-50 days from the end of March until this number has fallen to negligible levels. Taking the initial increase in the number of deaths for Germany, and combining this with typical values for the mortality reported in the literature and the published number of daily contacts for the working population, we calculated an initial increase in infections of 20 per day by a single infected person with an average human-human contact number of 22, decreasing to 5.5 after the first 10 days. The high number at the outset is likely related to outbreaks in a high local concentration of people.", "qid": 35, "docid": "ita70a52", "rank": 40, "score": 8.241100311279297}, {"content": "Title: Twitter sentiment classification for measuring public health concerns Content: An important task of public health officials is to keep track of health issues, such as spreading epidemics. In this paper, we are addressing the issue of spreading public concern about epidemics. Public concern about a communicable disease can be seen as a problem of its own. Keeping track of trends in concern about public health and identifying peaks of public concern are therefore crucial tasks. However, monitoring public health concerns is not only expensive with traditional surveillance systems, but also suffers from limited coverage and significant delays. To address these problems, we are using Twitter messages, which are available free of cost, are generated world-wide, and are posted in real time. We are measuring public concern using a two-step sentiment classification approach. In the first step, we distinguish Personal tweets from News (i.e., Non-Personal) tweets. In the second step, we further separate Personal Negative from Personal Non-Negative tweets. Both these steps consist themselves of two sub-steps. In the first sub-step (of both steps), our programs automatically generate training data using an emotion-oriented, clue-based method. In the second sub-step, we are training and testing three different Machine Learning (ML) models with the training data from the first sub-step; this allows us to determine the best ML model for different datasets. Furthermore, we are testing the already trained ML models with a human annotated, disjoint dataset. Based on the number of tweets classified as Personal Negative, we compute a Measure of Concern (MOC) and a timeline of the MOC. We attempt to correlate peaks of the MOC timeline to peaks of the News (Non-Personal) timeline. Our best accuracy results are achieved using the two-step method with a Na\u00efve Bayes classifier for the Epidemic domain (six datasets) and the Mental Health domain (three datasets).", "qid": 35, "docid": "vsl94lhz", "rank": 41, "score": 8.131500244140625}, {"content": "Title: Preliminary analysis of COVID-19 academic information patterns: a call for open science in the times of closed borders Content: The Pandemic of COVID-19, an infectious disease caused by SARS-CoV-2 motivated the scientific community to work together in order to gather, organize, process and distribute data on the novel biomedical hazard. Here, we analyzed how the scientific community responded to this challenge by quantifying distribution and availability patterns of the academic information related to COVID-19. The aim of this study was to assess the quality of the information flow and scientific collaboration, two factors we believe to be critical for finding new solutions for the ongoing pandemic. The RISmed R package, and a custom Python script were used to fetch metadata on articles indexed in PubMed and published on Rxiv preprint server. Scopus was manually searched and the metadata was exported in BibTex file. Publication rate and publication status, affiliation and author count per article, and submission-to-publication time were analysed in R. Biblioshiny application was used to create a world collaboration map. Preliminary data suggest that COVID-19 pandemic resulted in generation of a large amount of scientific data, and demonstrates potential problems regarding the information velocity, availability, and scientific collaboration in the early stages of the pandemic. More specifically, the results indicate precarious overload of the standard publication systems, significant problems with data availability and apparent deficient collaboration. In conclusion, we believe the scientific community could have used the data more efficiently in order to create proper foundations for finding new solutions for the COVID-19 pandemic. Moreover, we believe we can learn from this on the go and adopt open science principles and a more mindful approach to COVID-19-related data to accelerate the discovery of more efficient solutions. We take this opportunity to invite our colleagues to contribute to this global scientific collaboration by publishing their findings with maximal transparency.", "qid": 35, "docid": "ejgdzc70", "rank": 42, "score": 8.130999565124512}, {"content": "Title: What is the people posting about symptoms related to Coronavirus in Bogota, Colombia? Content: During the last months, there is an increasing alarm about a new mutation of coronavirus, covid-19 coined by World Health Organization(WHO) with an impact in many areas: economy, health, politics and others. This situation was declared a pandemic by WHO, because of the fast expansion over many countries. At the same time, people is using Social Networks to express what they think, feel or experiment, so this people are Social Sensors and helps to analyze what is happening in their city. The objective of this paper is analyze the publications of Colombian people living in Bogota with a radius of 50 km using Text Mining techniques from symptomatology approach. The results support the understanding of the spread in Colombia related to symptoms of covid19.", "qid": 35, "docid": "6jiy0b55", "rank": 43, "score": 8.123900413513184}, {"content": "Title: On the Generation of Medical Dialogues for COVID-19 Content: Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets -- CovidDialog -- (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog tasks. We perform both automatic and human evaluation of responses generated by these models. The results show that the generated responses are promising in being doctor-like, relevant to the conversation history, and clinically informative. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue.", "qid": 35, "docid": "czvyk0rk", "rank": 44, "score": 8.116100311279297}, {"content": "Title: A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration. Content: As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "qid": 35, "docid": "1lisdjpm", "rank": 45, "score": 8.105400085449219}, {"content": "Title: A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration Content: As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "qid": 35, "docid": "21fhsooy", "rank": 46, "score": 8.105399131774902}, {"content": "Title: Daily growth rate of scientific production on Covid-19. Analysis in databases and open access repositories Content: The scientific community is facing one of its greatest challenges in solving a global health problem: COVID-19 pandemic. This situation has generated an unprecedented volume of publications. What is the volume, in terms of publications, of research on COVID-19? The general objective of this research work is to obtain a global vision of the daily growth of scientific production on COVID-19 in different databases (Dimensions, Web of Science Core Collection, Scopus-Elsevier, Pubmed and eight repositories). In relation to the results obtained, Dimensions indexes a total of 9435 publications (69% with peer review and 2677 preprints) well above Scopus (1568) and WoS (718). This is a classic biliometric phenomenon of exponential growth (R2 = 0.92). The global growth rate is 500 publications and the production doubles every 15 days. In the case of Pubmed the weekly growth is around 1000 publications. Of the eight repositories analysed, Pubmed Central, Medrxiv and SSRN are the leaders. Despite their enormous contribution, the journals continue to be the core of scientific communication. Finally, it has been established that three out of every four publications on the COVID-19 are available in open access. The information explosion demands a serious and coordinated response from information professionals, which places us at the centre of the information pandemic.", "qid": 35, "docid": "25mu0mo9", "rank": 47, "score": 8.068900108337402}, {"content": "Title: Understanding Economic and Health Factors Impacting the Spread of COVID-19 Disease Content: The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely-populated areas. Aiming at bringing more light on key economic and public health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly-available COVID-19 datasets. The study had shown and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We have also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study has identified potential COVID-19 under-reporting traits as well as various economic factors that impact COVID-19 Diagnosis, Reporting, and Treatment. Based on the country clusters, we have also described the four disease development scenarios, which are tightly knit to country-level economic and public health factors. Finally, we have highlighted the potential limitation of reporting and measuring COVID-19 and provided recommendations on further in-depth quantitative research.", "qid": 35, "docid": "keaxietu", "rank": 48, "score": 8.058699607849121}, {"content": "Title: A Look at the First Quarantined Community in the USA: Response of Religious Communal Organizations and Implications for Public Health During the COVID-19 Pandemic Content: The current study examined anxiety and distress among members of the first community to be quarantined in the USA due to the COVID-19 pandemic. In addition to being historically significant, the current sample was unusual in that those quarantined were all members of a Modern Orthodox Jewish community and were connected via religious institutions at which exposure may have occurred. We sought to explore the community and religious factors unique to this sample, as they relate to the psychological and public health impact of quarantine. Community organizations were trusted more than any other source of COVID-19-related information, including federal, state and other government agencies, including the CDC, WHO and media news sources. This was supported qualitatively with open-ended responses in which participants described the range of supports organized by community organizations. These included tangible needs (i.e., food delivery), social support, virtual religious services, and dissemination of COVID-19-related information. The overall levels of distress and anxiety were elevated and directly associated with what was reported to be largely inadequate and inconsistent health-related information received from local departments of health. In addition, the majority of participants felt that perception of or concern about future stigma related to a COVID-19 diagnosis or association of COVID-19 with the Jewish community was high and also significantly predicted distress and anxiety. The current study demonstrates the ways in which religious institutions can play a vital role in promoting the well-being of their constituents. During this unprecedented pandemic, public health authorities have an opportunity to form partnerships with religious institutions in the common interests of promoting health, relaying accurate information and supporting the psychosocial needs of community members, as well as protecting communities against stigma and discrimination.", "qid": 35, "docid": "arexn6f8", "rank": 49, "score": 8.045999526977539}, {"content": "Title: COVID-19: What are the risks in hypertensive patients? Content: Considering the number of patients affected by SARS-CoV-2, the World Health Organization declared a pandemic on 11 March 2020. A number of publications regarding the course of COVID-19 infection and its relation to comorbidities have appeared since December 2019, when the first cases of atypical pneumonia were diagnosed in China. There is evidence of the higher susceptibility and higher risk of unfavourable outcomes in comorbid patients, including those with hypertension. We summarize the available data on the association with the COVID-19 infection and arterial hypertension, and discuss potential risks, e. g. the risks and benefits of antihypertensive therapy (in particular, related to the blockers of renin-angiotensin-aldosterone system) and the management approaches.", "qid": 35, "docid": "ta9g9ceh", "rank": 50, "score": 8.043100357055664}, {"content": "Title: Classification Aware Neural Topic Model and its Application on a New COVID-19 Disinformation Corpus Content: The explosion of disinformation related to the COVID-19 pandemic has overloaded fact-checkers and media worldwide. To help tackle this, we developed computational methods to support COVID-19 disinformation debunking and social impacts research. This paper presents: 1) the currently largest available manually annotated COVID-19 disinformation category dataset; and 2) a classification-aware neural topic model (CANTM) that combines classification and topic modelling under a variational autoencoder framework. We demonstrate that CANTM efficiently improves classification performance with low resources, and is scalable. In addition, the classification-aware topics help researchers and end-users to better understand the classification results.", "qid": 35, "docid": "v5m8vmr3", "rank": 51, "score": 8.034899711608887}, {"content": "Title: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study Content: Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35\u201360). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0\u00b70009). Although our sample captures only 507 (5\u00b72%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.", "qid": 35, "docid": "faec051u", "rank": 52, "score": 7.997000217437744}, {"content": "Title: BIP4COVID19: Releasing impact measures for articles relevant to COVID-19 Content: Since the beginning of the 2019-20 coronavirus pandemic, a large number of relevant articles has been published or become available in preprint servers. These articles, along with earlier related literature, compose a valuable knowledge base affecting contemporary research studies, or even government actions to limit the spread of the disease and treatment decisions taken by physicians. However, the number of such articles is increasing at an intense rate making the exploration of the relevant literature and the identification of useful knowledge in it challenging. In this work, we describe BIP4COVID19, an open dataset compiled to facilitate the coronavirus-related literature exploration, by providing various indicators of scientific impact for the relevant articles. Finally, we provide a publicly accessible Web interface on top of our data, allowing the exploration of the publications based on the computed indicators.", "qid": 35, "docid": "6xkm2j0f", "rank": 53, "score": 7.945700168609619}, {"content": "Title: CoV-Seq: SARS-CoV-2 Genome Analysis and Visualization Content: Summary COVID-19 has become a global pandemic not long after its inception in late 2019. SARS-CoV-2 genomes are being sequenced and shared on public repositories at a fast pace. To keep up with these updates, scientists need to frequently refresh and reclean datasets, which is ad hoc and labor-intensive. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. In order to address these challenges, we developed CoV-Seq, a webserver to enable simple and rapid analysis of SARS-CoV-2 genomes. Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are presented in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is also available for high-throughput processing. Availability and Implementation CoV-Seq is implemented in Python and Javascript. The webserver is available at http://covseq.baidu.com/ and the source code is available from https://github.com/boxiangliu/covseq. Contact jollier.liu@gmail.com Supplementary information Supplementary information are available at bioRxiv online.", "qid": 35, "docid": "nqfo3qtb", "rank": 54, "score": 7.936500072479248}, {"content": "Title: CoroNet: A Deep Neural Network for Detection and Diagnosis of COVID-19 from Chest X-ray Images Content: BACKGROUND AND OBJECTIVE: The novel Coronavirus also called COVID-19 originated in Wuhan, China in December 2019 and has now spread across the world. It has so far infected around 1.8 million people and claimed approximately 114698 lives overall. As the number of cases are rapidly increasing, most of the countries are facing shortage of testing kits and resources. The limited quantity of testing kits and increasing number of daily cases encouraged us to come up with a Deep Learning model that can aid radiologists and clinicians in detecting COVID-19 cases using chest X-rays. METHODS: In this study, we propose CoroNet, a Deep Convolutional Neural Network model to automatically detect COVID-19 infection from chest X-ray images. The proposed model is based on Xception architecture pre-trained on ImageNet dataset and trained end-to-end on a dataset prepared by collecting COVID-19 and other chest pneumonia X-ray images from two different publically available databases. RESULTS: CoroNet has been trained and tested on the prepared dataset and the experimental results show that our proposed model achieved an overall accuracy of 89.6%, and more importantly the precision and recall rate for COVID-19 cases are 93% and 98.2% for 4-class cases (COVID vs Pneumonia bacterial vs pneumonia viral vs normal). For 3-class classification (COVID vs Pneumonia vs normal), the proposed model produced a classification accuracy of 95%. The preliminary results of this study look promising which can be further improved as more training data becomes available. CONCLUSION: CoroNet achieved promising results on a small prepared dataset which indicates that given more data, the proposed model can achieve better results with minimum pre-processing of data. Overall, the proposed model substantially advances the current radiology based methodology and during COVID-19 pandemic, it can be very helpful tool for clinical practitioners and radiologists to aid them in diagnosis, quantification and follow-up of COVID-19 cases.", "qid": 35, "docid": "4p1ah2h3", "rank": 55, "score": 7.936399936676025}, {"content": "Title: CoroNet: A deep neural network for detection and diagnosis of COVID-19 from chest x-ray images Content: BACKGROUND AND OBJECTIVE: The novel Coronavirus also called COVID-19 originated in Wuhan, China in December 2019 and has now spread across the world. It has so far infected around 1.8 million people and claimed approximately 114,698 lives overall. As the number of cases are rapidly increasing, most of the countries are facing shortage of testing kits and resources. The limited quantity of testing kits and increasing number of daily cases encouraged us to come up with a Deep Learning model that can aid radiologists and clinicians in detecting COVID-19 cases using chest X-rays. METHODS: In this study, we propose CoroNet, a Deep Convolutional Neural Network model to automatically detect COVID-19 infection from chest X-ray images. The proposed model is based on Xception architecture pre-trained on ImageNet dataset and trained end-to-end on a dataset prepared by collecting COVID-19 and other chest pneumonia X-ray images from two different publically available databases. RESULTS: CoroNet has been trained and tested on the prepared dataset and the experimental results show that our proposed model achieved an overall accuracy of 89.6%, and more importantly the precision and recall rate for COVID-19 cases are 93% and 98.2% for 4-class cases (COVID vs Pneumonia bacterial vs pneumonia viral vs normal). For 3-class classification (COVID vs Pneumonia vs normal), the proposed model produced a classification accuracy of 95%. The preliminary results of this study look promising which can be further improved as more training data becomes available. CONCLUSION: CoroNet achieved promising results on a small prepared dataset which indicates that given more data, the proposed model can achieve better results with minimum pre-processing of data. Overall, the proposed model substantially advances the current radiology based methodology and during COVID-19 pandemic, it can be very helpful tool for clinical practitioners and radiologists to aid them in diagnosis, quantification and follow-up of COVID-19 cases.", "qid": 35, "docid": "s9yxh8ut", "rank": 56, "score": 7.936398983001709}, {"content": "Title: Towards Efficient COVID-19 CT Annotation: A Benchmark for Lung and Infection Segmentation Content: Accurate segmentation of lung and infection in COVID-19 CT scans plays an important role in the quantitative management of patients. Most of the existing studies are based on large and private annotated datasets that are impractical to obtain from a single institution, especially when radiologists are busy fighting the coronavirus disease. Furthermore, it is hard to compare current COVID-19 CT segmentation methods as they are developed on different datasets, trained in different settings, and evaluated with different metrics. In this paper, we created a COVID-19 3D CT dataset with 20 cases that contains 1800+ annotated slices and made it publicly available. To promote the development of annotation-efficient deep learning methods, we built three benchmarks for lung and infection segmentation that contain current main research interests, e.g., few-shot learning, domain generalization, and knowledge transfer. For a fair comparison among different segmentation methods, we also provide unified training, validation and testing dataset splits, and evaluation metrics and corresponding code. In addition, we provided more than 40 pre-trained baseline models for the benchmarks, which not only serve as out-of-the-box segmentation tools but also save computational time for researchers who are interested in COVID-19 lung and infection segmentation. To the best of our knowledge, this work presents the largest public annotated COVID-19 CT volume dataset, the first segmentation benchmark, and the most pre-trained models up to now. We hope these resources (\\url{https://gitee.com/junma11/COVID-19-CT-Seg-Benchmark}) could advance the development of deep learning methods for COVID-19 CT segmentation with limited data.", "qid": 35, "docid": "tvmytgda", "rank": 57, "score": 7.926199913024902}, {"content": "Title: Potential of age distribution profiles for the prediction of COVID-19 infection origin in a patient group Content: The COVID-19 pandemic is a serious and global public health concern. It is now well known that COVID-19 cases may result in mild symptoms leading to patient recovery. However, severity of infection, fatality rates, and treatment responses across different countries, age groups, and demographic groups suggest that the nature of infection is diverse, and a timely investigation of the same is needed for evolving sound treatment and preventive strategies. This paper reports an the analysis of age distribution patterns in six groups of Indian COVID-19 patient populations based on their likely geographical origin of infection viz. the United Kingdom, North America, the European Union, the Middle East, and Asian countries. It was observed that patient groups stratified in this way had a distinct age profile and that some of these groups e.g. patient groups from Asia, the European Union, and the United Kingdom formed a different cluster than those from North America, the Middle East, and other regions. Patient age profiles of a population were found to be highly predictive of the group they belong to, and there are indications of their distinct recovery and fatality rates across gender. Altogether this study provides a scalable framework to estimate the source of infection in a new population of COVID-19 patients with unknown origin. It is also concluded that greater public availability of age and other demographic profile details of patients may be helpful in gaining robust insights into COVID-19 infection origins. Datasets and scripts used in this work are shared at http://covid.sciwhylab.org.", "qid": 35, "docid": "0m5mc320", "rank": 58, "score": 7.917799949645996}, {"content": "Title: TweetsCOV19 -- A Knowledge Base of Semantically Annotated Tweets about the COVID-19 Pandemic Content: Publicly available social media archives facilitate research in the social sciences and provide corpora for training and testing a wide range of machine learning, NLP and information retrieval methods. With respect to the recent outbreak of COVID-19, online discourse on Twitter reflects public opinion and perception related to the pandemic itself as well as mitigating measures and their societal impact. Understanding such discourse, its evolution and interdependencies with real-world events or (mis)information can foster valuable insights. On the other hand, such corpora are crucial facilitators for computational methods addressing tasks such as sentiment analysis, event detection or entity recognition. However, obtaining, archiving and semantically annotating large amounts of tweets is costly. In this paper, we describe TweetsCOV19, a publicly available knowledge base of currently more than 8 million tweets, spanning the period Oct'19-Apr'20. Metadata about the tweets as well as extracted entities, hashtags, user mentions, sentiments, and URLs are exposed using established RDF/S vocabularies, providing an unprecedented knowledge base for a range of knowledge discovery tasks. Next to a description of the dataset and its extraction and annotation process, we present an initial analysis, use cases and usage of the corpus.", "qid": 35, "docid": "aj2kscs9", "rank": 59, "score": 7.890200138092041}, {"content": "Title: Enhanced COVID-19 data for improved prediction of survival Content: The current COVID-19 pandemic, caused by the rapid world-wide spread of the SARS-CoV-2 virus, is having severe consequences for human health and the world economy. The virus effects individuals quite differently, with many infected patients showing only mild symptoms, and others showing critical illness. To lessen the impact of the pandemic, one important question is which factors predict the death of a patient? Here, we construct an enhanced COVID-19 dataset by processing two existing databases (from Kaggle and WHO) and using natural language processing methods to enhance the data by adding local weather conditions and research sentiment. Author summary In this study, we contribute an enhanced COVID-19 dataset, which contains 183 samples and 43 features. Application of Extreme Gradient Boosting (XGBoost) on the enhanced dataset achieves 95% accuracy in predicting patients survival, with country-wise research sentiment, and then age and local weather, showing the most importance. All data and source code are available at http://ab.inf.uni-tuebingen.de/publications/papers/COVID-19.", "qid": 35, "docid": "vznb3puk", "rank": 60, "score": 7.888599872589111}, {"content": "Title: COVID-19 Detection in Chest X-ray Images using a Deep Learning Approach Content: The Corona Virus Disease (COVID-19) is an infectious disease caused by a new virus that has not been detected in humans before The virus causes a respiratory illness like the flu with various symptoms such as cough or fever that, in severe cases, may cause pneumonia The COVID-19 spreads so quickly between people, affecting to 1,200,000 people worldwide at the time of writing this paper (April 2020) Due to the number of contagious and deaths are continually growing day by day, the aim of this study is to develop a quick method to detect COVID-19 in chest X-ray images using deep learning techniques For this purpose, an object detection architecture is proposed, trained and tested with a public available dataset composed with 1500 images of non-infected patients and infected with COVID-19 and pneumonia The main goal of our method is to classify the patient status either negative or positive COVID-19 case In our experiments using SDD300 model we achieve a 94 92% of sensibility and 92 00% of specificity in COVID-19 detection, demonstrating the usefulness application of deep learning models to classify COVID-19 in X-ray images", "qid": 35, "docid": "af95gxvb", "rank": 61, "score": 7.865600109100342}, {"content": "Title: Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England Content: The NHS Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.", "qid": 35, "docid": "vpxe8e9d", "rank": 62, "score": 7.860300064086914}, {"content": "Title: COVID-19-CT-CXR: a freely accessible and weakly labeled chest X-ray and CT image collection on COVID-19 from biomedical literature Content: The latest threat to global health is the COVID-19 outbreak. Although there exist large datasets of chest X-rays (CXR) and computed tomography (CT) scans, few COVID-19 image collections are currently available due to patient privacy. At the same time, there is a rapid growth of COVID-19-relevant articles in the biomedical literature. Here, we present COVID-19-CT-CXR, a public database of COVID-19 CXR and CT images, which are automatically extracted from COVID-19-relevant articles from the PubMed Central Open Access (PMC-OA) Subset. We extracted figures, associated captions, and relevant figure descriptions in the article and separated compound figures into subfigures. We also designed a deep-learning model to distinguish them from other figure types and to classify them accordingly. The final database includes 1,327 CT and 263 CXR images (as of May 9, 2020) with their relevant text. To demonstrate the utility of COVID-19-CT-CXR, we conducted four case studies. (1) We show that COVID-19-CT-CXR, when used as additional training data, is able to contribute to improved DL performance for the classification of COVID-19 and non-COVID-19 CT. (2) We collected CT images of influenza and trained a DL baseline to distinguish a diagnosis of COVID-19, influenza, or normal or other types of diseases on CT. (3) We trained an unsupervised one-class classifier from non-COVID-19 CXR and performed anomaly detection to detect COVID-19 CXR. (4) From text-mined captions and figure descriptions, we compared clinical symptoms and clinical findings of COVID-19 vs. those of influenza to demonstrate the disease differences in the scientific publications. We believe that our work is complementary to existing resources and hope that it will contribute to medical image analysis of the COVID-19 pandemic. The dataset, code, and DL models are publicly available at https://github.com/ncbi-nlp/COVID-19-CT-CXR.", "qid": 35, "docid": "ijceqi3y", "rank": 63, "score": 7.81220006942749}, {"content": "Title: COVID-19-CT-CXR: a freely accessible and weakly labeled chest X-ray and CT image collection on COVID-19 from biomedical literature. Content: The latest threat to global health is the COVID-19 outbreak. Although there exist large datasets of chest X-rays (CXR) and computed tomography (CT) scans, few COVID-19 image collections are currently available due to patient privacy. At the same time, there is a rapid growth of COVID-19-relevant articles in the biomedical literature. Here, we present COVID-19-CT-CXR, a public database of COVID-19 CXR and CT images, which are automatically extracted from COVID-19-relevant articles from the PubMed Central Open Access (PMC-OA) Subset. We extracted figures, associated captions, and relevant figure descriptions in the article and separated compound figures into subfigures. We also designed a deep-learning model to distinguish them from other figure types and to classify them accordingly. The final database includes 1,327 CT and 263 CXR images (as of May 9, 2020) with their relevant text. To demonstrate the utility of COVID-19-CT-CXR, we conducted four case studies. (1) We show that COVID-19-CT-CXR, when used as additional training data, is able to contribute to improved DL performance for the classification of COVID-19 and non-COVID-19 CT. (2) We collected CT images of influenza and trained a DL baseline to distinguish a diagnosis of COVID-19, influenza, or normal or other types of diseases on CT. (3) We trained an unsupervised one-class classifier from non-COVID-19 CXR and performed anomaly detection to detect COVID-19 CXR. (4) From text-mined captions and figure descriptions, we compared clinical symptoms and clinical findings of COVID-19 vs. those of influenza to demonstrate the disease differences in the scientific publications. We believe that our work is complementary to existing resources and hope that it will contribute to medical image analysis of the COVID-19 pandemic. The dataset, code, and DL models are publicly available at https://github.com/ncbi-nlp/COVID-19-CT-CXR.", "qid": 35, "docid": "uqfygev4", "rank": 64, "score": 7.812199115753174}, {"content": "Title: $\\alpha$-Satellite: An AI-driven System and Benchmark Datasets for Hierarchical Community-level Risk Assessment to Help Combat COVID-19 Content: The novel coronavirus and its deadly outbreak have posed grand challenges to human society: as of March 26, 2020, there have been 85,377 confirmed cases and 1,293 reported deaths in the United States; and the World Health Organization (WHO) characterized coronavirus disease (COVID-19) - which has infected more than 531,000 people with more than 24,000 deaths in at least 171 countries - a global pandemic. A growing number of areas reporting local sub-national community transmission would represent a significant turn for the worse in the battle against the novel coronavirus, which points to an urgent need for expanded surveillance so we can better understand the spread of COVID-19 and thus better respond with actionable strategies for community mitigation. By advancing capabilities of artificial intelligence (AI) and leveraging the large-scale and real-time data generated from heterogeneous sources (e.g., disease related data from official public health organizations, demographic data, mobility data, and user geneated data from social media), in this work, we propose and develop an AI-driven system (named $\\alpha$-Satellite}, as an initial offering, to provide hierarchical community-level risk assessment to assist with the development of strategies for combating the fast evolving COVID-19 pandemic. More specifically, given a specific location (either user input or automatic positioning), the developed system will automatically provide risk indexes associated with it in a hierarchical manner (e.g., state, county, city, specific location) to enable individuals to select appropriate actions for protection while minimizing disruptions to daily life to the extent possible. The developed system and the generated benchmark datasets have been made publicly accessible through our website. The system description and disclaimer are also available in our website.", "qid": 35, "docid": "ns628u21", "rank": 65, "score": 7.804900169372559}, {"content": "Title: Expression of ACE2, the SARS-CoV-2 receptor, and TMPRSS2 in prostate epithelial cells Content: The COVID-19 pandemic has spread across more than 200 countries and resulted in over 170,000 deaths. For unclear reasons, higher mortality rates from COVID-19 have been reported in men compared to women. While the SARS-CoV-2 receptor ACE2 and serine protease TMPRSS2 have been detected in lung and other tissues, it is not clear what sex differences may exist. We analyzed a publicly-available normal human prostate single-cell RNA sequencing dataset and found TMPRSS2 and ACE2 co-expressing cells in epithelial cells, with a higher proportion in club and hillock cells. Then we investigated datasets of lung epithelial cells and also found club cells co-expressing TMPRSS2 and ACE2. A comparison of ACE2 expression in lung tissue between males and females showed higher expression in males and a larger proportion of ACE2+ cells in male type II pneumocytes, with preliminary evidence that type II pneumocytes of all lung epithelial cell types showed the highest expression of ACE2. These results raise the possibility that sex differences in ACE2 expression and the presence of double-positive cells in the prostate may contribute to the observed disparities of COVID-19.", "qid": 35, "docid": "rbhpe5wx", "rank": 66, "score": 7.786399841308594}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 35, "docid": "fqs40ivc", "rank": 67, "score": 7.736199855804443}, {"content": "Title: A County-level Dataset for Informing the United States' Response to COVID-19 Content: As the coronavirus disease 2019 (COVID-19) becomes a global pandemic, policy makers must enact interventions to stop its spread. Data driven approaches might supply information to support the implementation of mitigation and suppression strategies. To facilitate research in this direction, we present a machine-readable dataset that aggregates relevant data from governmental, journalistic, and academic sources on the county level. In addition to county-level time-series data from the JHU CSSE COVID-19 Dashboard, our dataset contains more than 300 variables that summarize population estimates, demographics, ethnicity, housing, education, employment and in come, climate, transit scores, and healthcare system-related metrics. Furthermore, we present aggregated out-of-home activity information for various points of interest for each county, including grocery stores and hospitals, summarizing data from SafeGraph. By collecting these data, as well as providing tools to read them, we hope to aid researchers investigating how the disease spreads and which communities are best able to accommodate stay-at-home mitigation efforts. Our dataset and associated code are available at https://github.com/JieYingWu/COVID-19_US_County-level_Summaries.", "qid": 35, "docid": "rndc2v2b", "rank": 68, "score": 7.718100070953369}, {"content": "Title: Fast and accurate detection of Covid-19-related pneumonia from chest X-ray images with novel deep learning model Content: Background: Novel coronavirus disease has spread rapidly worldwide. As recent radiological literatures on Covid-19 related pneumonia is primarily focused on CT findings, the American College of Radiology (ACR) recommends using portable chest X-radiograph (CXR). A tool to assist for detection and monitoring of Covid-19 cases from CXR is highly required. Purpose: To develop a fully automatic framework to detect Covid-19 related pneumonia using CXR images and evaluate its performance. Materials and Methods: In this study, a novel deep learning model, named CovIDNet (Covid-19 Indonesia Neural-Network), was developed to extract visual features from chest x-ray images for the detection of Covid-19 related pneumonia. The model was trained and validated by chest x-rays datasets collected from several open source provided by GitHub and Kaggle. Results and Discussion: In the validation stage using open-source data, the accuracy to recognize Covid-19 and others classes reaches 98.44%, that is, 100% Covid-19 precision and 97% others precision. Discussion: The use of the model to classify Covid-19 and other pathologies might slightly decrease the accuracy. Although SoftMax was used to handle classification bias, this indicates the benefit of additional training upon the introduction of new set of data. Conclusion: The model has been tested and get 98.4% accuracy for open source datasets, the sensitivity and specificity are 100% and 96.97%, respectively.", "qid": 35, "docid": "24xef6ay", "rank": 69, "score": 7.673999786376953}, {"content": "Title: The Efficacy of Lockdown Against COVID-19: A Cross-Country Panel Analysis Content: BACKGROUND: There has been much debate about the effectiveness of lockdown measures in containing COVID-19, and their appropriateness given the economic and social cost they entail. To the best of our knowledge, no existing contribution to the literature has attempted to gauge the effectiveness of lockdown measures over time in a longitudinal cross-country perspective. OBJECTIVES: This paper aims to fill the gap in the literature by assessing, at an international level, the effect of lockdown measures (or the lack of such measures) on the numbers of new infections. Given this policy\u2019s expected change in effectiveness over time, we also measure the effect of having a lockdown implemented over a given number of days (from 7 to 20 days). METHODS: We pursue our objectives by means of a quantitative panel analysis, building a longitudinal dataset with observations from countries all over the world, and estimating the impact of lockdown via feasible generalized least squares fixed effect, random effects, generalized estimating equation, and hierarchical linear models. RESULTS: Our results show that lockdown is effective in reducing the number of new cases in the countries that implement it, compared with those countries that do not. This is especially true around 10 days after the implementation of the policy. Its efficacy continues to grow up to 20 days after implementation. CONCLUSION: Results suggest that lockdown is effective in reducing the R0, i.e. the number of people infected by each infected person, and that, unlike what has been suggested in previous analyses, its efficacy continues to hold 20 days after the introduction of the policy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40258-020-00596-3) contains supplementary material, which is available to authorized users.", "qid": 35, "docid": "fi6t2e0u", "rank": 70, "score": 7.660299777984619}, {"content": "Title: COVID-CT-Dataset: A CT Scan Dataset about COVID-19 Content: During the outbreak time of COVID-19, computed tomography (CT) is a useful manner for diagnosing COVID-19 patients. Due to privacy issues, publicly available COVID-19 CT datasets are highly difficult to obtain, which hinders the research and development of AI-powered diagnosis methods of COVID-19 based on CTs. To address this issue, we build an open-sourced dataset -- COVID-CT, which contains 349 COVID-19 CT images from 216 patients and 463 non-COVID-19 CTs. The utility of this dataset is confirmed by a senior radiologist who has been diagnosing and treating COVID-19 patients since the outbreak of this pandemic. We also perform experimental studies which further demonstrate that this dataset is useful for developing AI-based diagnosis models of COVID-19. Using this dataset, we develop diagnosis methods based on multi-task learning and self-supervised learning, that achieve an F1 of 0.90, an AUC of 0.98, and an accuracy of 0.89. According to the senior radiologist, models with such performance are good enough for clinical usage. The data and code are available at https://github.com/UCSD-AI4H/COVID-CT", "qid": 35, "docid": "55nifoqu", "rank": 71, "score": 7.6585001945495605}, {"content": "Title: A COVID-19 epidemic model integrating direct and fomite transmission as well as household structure Content: This paper stresses its base contribution on a new SIR-type model for COVID-19 including direct and fomite transmission as well as the effect of distinct household structures. To what extent increasing the physical-distancing-related contact radius and enhancing mass control (public curfew, lockdown, workplace clearance, and school closure) reduce the number of predicted active cases is studied via parameter estimation.", "qid": 35, "docid": "k3gylwcf", "rank": 72, "score": 7.640999794006348}, {"content": "Title: A Cascaded Learning Strategy for Robust COVID-19 Pneumonia Chest X-Ray Screening Content: We introduce a comprehensive screening platform for the COVID-19 (a.k.a., SARS-CoV-2) pneumonia. The proposed AI-based system works on chest x-ray (CXR) images to predict whether a patient is infected with the COVID-19 disease. Although the recent international joint effort on making the availability of all sorts of open data, the public collection of CXR images is still relatively small for reliably training a deep neural network (DNN) to carry out COVID-19 prediction. To better address such inefficiency, we design a cascaded learning strategy to improve both the sensitivity and the specificity of the resulting DNN classification model. Our approach leverages a large CXR image dataset of non-COVID-19 pneumonia to generalize the original well-trained classification model via a cascaded learning scheme. The resulting screening system is shown to achieve good classification performance on the expanded dataset, including those newly added COVID-19 CXR images.", "qid": 35, "docid": "tupom7fb", "rank": 73, "score": 7.631999969482422}, {"content": "Title: A citizen science initiative for open data and visualization of COVID-19 outbreak in Kerala, India Content: India, the second most populated country in the world, reported its first COVID-19 case in the state of Kerala with a travel history from Wuhan. Subsequently, a surge of cases was observed in the state mainly through the individuals who traveled from Europe and the Middle East to Kerala, thus initiating an outbreak. Since public awareness through dissemination of reliable information plays a significant role in controlling the spread of the disease, the Department of Health Services, Government of Kerala initially released daily updates through daily textual bulletins. However, this unstructured data requires refinement and enrichment for upstream applications, such as visualization, and/or analysis. Here we reported a citizen science initiative that leveraged publicly available and crowd-verified data on COVID-19 outbreak in Kerala from the government bulletins, supplemented with the information from media outlets to generate reusable datasets. This data was further used to provide real-time analysis, and daily updates of COVID-19 cases in Kerala, through a user-friendly bilingual dashboard (https://covid19kerala.info/) for non-specialists. We ensured longevity and reusability of the dataset by depositing it in a public repository, aligning with open source principles for future analytical efforts. Finally, to show the scope of the sourced data, we also provided a snapshot of outbreak trends and demographic characteristics of the individuals affected with COVID-19 in Kerala during the first 99 days of the outbreak.", "qid": 35, "docid": "nbzbmrsd", "rank": 74, "score": 7.631100177764893}, {"content": "Title: Semiparametric Bayesian Inference for the Transmission Dynamics of COVID-19 with a State-Space Model Content: The outbreak of Coronavirus Disease 2019 (COVID-19) is an ongoing pandemic affecting over 200 countries and regions. Inference about the transmission dynamics of COVID-19 can provide important insights into the speed of disease spread and the effects of mitigation policies. We develop a novel Bayesian approach to such inference based on a probabilistic compartmental model using data of daily confirmed COVID-19 cases. In particular, we consider a probabilistic extension of the classical susceptible-infectious-recovered model, which takes into account undocumented infections and allows the epidemiological parameters to vary over time. We estimate the disease transmission rate via a Gaussian process prior, which captures nonlinear changes over time without the need of specific parametric assumptions. We utilize a parallel-tempering Markov chain Monte Carlo algorithm to efficiently sample from the highly correlated posterior space. Predictions for future observations are done by sampling from their posterior predictive distributions. Performance of the proposed approach is assessed using simulated datasets. Finally, our approach is applied to COVID-19 data from four states of the United States: Washington, New York, California, and Illinois. An R package BaySIR is made available at https://github.com/tianjianzhou/BaySIR for the public to conduct independent analysis or reproduce the results in this paper.", "qid": 35, "docid": "3k9is4h6", "rank": 75, "score": 7.596199989318848}, {"content": "Title: Predicting the epidemic curve of the coronavirus (SARS-CoV-2) disease (COVID-19) using artificial intelligence Content: Objectives: The current form of severe acute respiratory syndrome called coronavirus disease 2019 (COVID19) caused by a coronavirus (SARSCoV2) is a major global health problem. The aim of our study was to use the official data and predict the possible outcomes of the COVID 19 pandemic using artificial intelligence (AI) based RNNs (Recurrent Neural Networks), then compare and validate the predicted and observed data. Materials and Methods: We used the publicly available datasets of World Health Organization and Johns Hopkins University to create the training dataset, then have used recurrent neural networks (RNNs) with gated recurring units (Long Short Term Memory: LSTM units) to create 2 Prediction Models. Information collected in the first t time steps were aggregated with a fully connected (dense) neural network layer and a consequent regression output layer to determine the next predicted value. We used root mean squared logarithmic errors (RMSLE) to compare the predicted and observed data, then recalculated the predictions again. Results: The result of our study underscores that the COVID19 pandemic is probably a propagated source epidemic, therefore repeated peaks on the epidemic curve (rise of the daily number of the newly diagnosed infections) are to be anticipated. The errors between the predicted and validated data and trends seems to be low. Conclusions: The influence of this pandemic is great worldwide, impact our everyday lifes. Especially decision makers must be aware, that even if strict public health measures are executed and sustained, future peaks of infections are possible. The AI based predictions might be useful tools for predictions and the models can be recalculated according to the new observed data, to get more precise forecast of the pandemic.", "qid": 35, "docid": "35xpmdbj", "rank": 76, "score": 7.56850004196167}, {"content": "Title: Exploring Epidemiological Behavior of Novel Coronavirus Outbreak through the Development and Analysis of COVID-19 Daily Dataset in Bangladesh Content: Globally, there is an obvious concern about the fact that the evolving 2019-nCoV coronavirus is a worldwide public health threat. The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019 triggered a major global epidemic, which is now a major community health issue. As of April 17, 2020, according to Institute of Epidemiology, Disease Control and Research (IEDCR) Bangladesh has reported 1838 confirmed cases in between 8 March to 17 April 2020, with > 4.08% of mortality rate and >3.15% of recovery rate. COVID-19 outbreak is evolving so rapidly in Bangladesh; therefore, the availability of epidemiological data and its sensible analysis are essential to direct strategies for situational awareness and intervention. This article presents an exploratory data analysis approach to collect and analyze COVID-19 data on epidemiological outbreaks based on first publicly available COVID-19 Daily Dataset of Bangladesh. Various publicly open data sources on the outbreak of COVID-19 provided by the IEDCR, World Health Organization (WHO), Directorate General of Health Services (DGHS), and Ministry of Health and Family Welfare (MHFW) of Bangladesh have been used in this research. A Visual Exploratory Data Analysis (V-EDA) techniques have been followed in this research to understand the epidemiological characteristics of COVID-19 outbreak in different districts of Bangladesh in between 8 March 2020 to 12 April 2020 and these findings were compared with those of other countries. In all, this is extremely important to promptly spread information to understand the risks of this pandemic and begin containment activities in the country.", "qid": 35, "docid": "bce1oeyl", "rank": 77, "score": 7.563300132751465}, {"content": "Title: Clustering of Covid-19 morbidity cases in Germany Content: The Covid-19 coronavirus has spread almost all over the world. Though it has been reported recently that the epidemic declines in China, in other countries it still hasn\u2019t achieved peak level. The data analysis methods may help struggling against the disease. The Covid-19 Tracking Germany dataset has been handled in the research. It\u2019s daily refreshed dataset available at the kaggle.com site. It contains information on number of fallen ill people in Germany. The cases are grouped by federal land, city, age diapason and date. The main goal of the research is to underline differences in morbidity registered in different lands of Germany. There have been published new suggestions about connection between coronavirus morbidity and BCG vaccination. This question is also taken into account. Analysis based on the handled dataset is able to make only oblique conclusions because of lack of information. Differences in coronavirus morbidity in various regions and various age groups are highlighted. The regions of Germany are clustered into groups by gravity of recent situation.", "qid": 35, "docid": "cszor0pd", "rank": 78, "score": 7.544400215148926}, {"content": "Title: Tracking Public Opinion in China through Various Stages of the COVID-19 Pandemic Content: In recent months, COVID-19 has become a global pandemic and had a huge impact on the world. People under different conditions have very different attitudes toward the epidemic. Due to the real-time and large-scale nature of social media, we can continuously obtain a massive amount of public opinion information related to the epidemic from social media. In particular, researchers may ask questions such as\"how is the public reacting to COVID-19 in China during different stages of the pandemic?\",\"what factors affect the public opinion orientation in China?\", and so on. To answer such questions, we analyze the pandemic related public opinion information on Weibo, China's largest social media platform. Specifically, we have first collected a large amount of COVID-19-related public opinion microblogs. We then use a sentiment classifier to recognize and analyze different groups of users' opinions. In the collected sentiment orientated microblogs, we try to track the public opinion through different stages of the COVID-19 pandemic. Furthermore, we analyze more key factors that might have an impact on the public opinion of COVID-19 (e.g., users in different provinces or users with different education levels). Empirical results show that the public opinions vary along with the key factors of COVID-19. Furthermore, we analyze the public attitudes on different public-concerning topics, such as staying at home and quarantine.", "qid": 35, "docid": "1rc2swfm", "rank": 79, "score": 7.539400100708008}, {"content": "Title: Oscillations in USA COVID-19 Incidence and Mortality Data reflect societal factors Content: The COVID-19 pandemic currently in process differs from other infectious disease calamities that have previously plagued humanity in the vast amount of information that is produces each day, which includes daily estimates of the disease incidence and mortality data. Apart from providing actionable information to public health authorities on the trend of the pandemic, the daily incidence reflects the process of disease in a susceptible population and thus reflects the pathogenesis of COVID-19, the public health response and diagnosis and reporting. Both daily new cases and daily mortality data in the US exhibit periodic oscillatory patterns. By analyzing NYC and LA testing data, we demonstrate that this oscillation in the number of cases can be strongly explained by the daily variation in testing. This seems to rule out alternative hypotheses such as increased infections on certain days of the week as driving this oscillation. Similarly, we show that the apparent oscillation in mortality in the US data is mostly an artifact of reporting, which disappears in datasets that record death by episode date, such as the NYC and LA datasets. Periodic oscillations in COVID-19 incidence and mortality data reflect testing and reporting practices and contingencies. Thus, these contingencies should be considered first prior to suggesting social or biological mechanisms.", "qid": 35, "docid": "q34w89fa", "rank": 80, "score": 7.533400058746338}, {"content": "Title: COVID-19 virus outbreak lockdown: What impacts on household food wastage? Content: The 2019\u20132020 coronavirus disease (COVID-19) is a public health issue. Lockdown is among options suggested to reduce spread of the virus. This study aimed to determining the impact of COVID-19 lockdown on Tunisian consumer awareness, attitudes and behaviors related to food wastage. An online survey was conducted during the first 2 weeks of COVID-19 lockdown. The survey collected information on demographic data, awareness and attitudes toward food waste, food purchase behavior and household food expenditure estimation; extent of household food waste; willingness and information needs to reduce food waste. This study included 284 respondents. About 89% of respondents claimed to be aware of food waste, and the COVID-19 lockdown would impact for 93% of respondents, their waste levels, and for 80%, their grocery shopping habits. Interestingly, the COVID-19 lockdown improved food shopping performances and pushed toward a positive behavioral change regarding food wastage: 85% respondents declared nothing of what they bought would be discarded, and most of the respondents have set up a strategy of saving, storing and eating leftovers. The most cited reasons given for discarding food were overcooking, inappropriate storage and overbuying. Consumers\u2019 changes in food waste prevention might be probably driven more by the socioeconomical context of the COVID-19 lockdown (i.e. food availability, restricted movements, loss of income), than by a pro-environmental concern. Finally, our study pointed out the consumers\u2019 needs of information for taking further action. In conclusion, our study can constitute a basis to further promote household food waste prevention behavior, outlasting the COVID-19 crisis.", "qid": 35, "docid": "nqca8mio", "rank": 81, "score": 7.519999980926514}, {"content": "Title: Momentum Contrastive Learning for Few-Shot COVID-19 Diagnosis from Chest CT Images Content: The current pandemic, caused by the outbreak of a novel coronavirus (COVID-19) in December 2019, has led to a global emergency that has significantly impacted economies, healthcare systems and personal wellbeing all around the world. Controlling the rapidly evolving disease requires highly sensitive and specific diagnostics. While real-time RT-PCR is the most commonly used, these can take up to 8 hours, and require significant effort from healthcare professionals. As such, there is a critical need for a quick and automatic diagnostic system. Diagnosis from chest CT images is a promising direction. However, current studies are limited by the lack of sufficient training samples, as acquiring annotated CT images is time-consuming. To this end, we propose a new deep learning algorithm for the automated diagnosis of COVID-19, which only requires a few samples for training. Specifically, we use contrastive learning to train an encoder which can capture expressive feature representations on large and publicly available lung datasets and adopt the prototypical network for classification. We validate the efficacy of the proposed model in comparison with other competing methods on two publicly available and annotated COVID-19 CT datasets. Our results demonstrate the superior performance of our model for the accurate diagnosis of COVID-19 based on chest CT images.", "qid": 35, "docid": "724br56j", "rank": 82, "score": 7.51140022277832}, {"content": "Title: Informative Ranking of Stand Out Collections of Symptoms: A New Data-Driven Approach to Identify the Strong Warning Signs of COVID 19 Content: We develop here a data-driven approach for disease recognition based on given symptoms, to be efficient tool for anomaly detection. In a clinical setting and when presented with a patient with a combination of traits, a doctor may wonder if a certain combination of symptoms may be especially predictive, such as the question,\"Are fevers more informative in women than men?\"The answer to this question is, yes. We develop here a methodology to enumerate such questions, to learn what are the stronger warning signs when attempting to diagnose a disease, called Conditional Predictive Informativity, (CPI), whose ranking we call CPIR. This simple to use process allows us to identify particularly informative combinations of symptoms and traits that may help medical field analysis in general, and possibly to become a new data-driven advised approach for individual medical diagnosis, as well as for broader public policy discussion. In particular we have been motivated to develop this tool in the current enviroment of the pressing world crisis due to the COVID 19 pandemic. We apply the methods here to data collected from national, provincial, and municipal health reports, as well as additional information from online, and then curated to an online publically available Github repository.", "qid": 35, "docid": "11rb5fdh", "rank": 83, "score": 7.509699821472168}, {"content": "Title: Informative Ranking of Stand Out Collections of Symptoms: A New Data-Driven Approach to Identify the Strong Warning Signs of COVID 19 Content: We develop here a data-driven approach for disease recognition based on given symptoms, to be efficient tool for anomaly detection. In a clinical setting and when presented with a patient with a combination of traits, a doctor may wonder if a certain combination of symptoms may be especially predictive, such as the question, \"Are fevers more informative in women than men?\" The answer to this question is, yes. We develop here a methodology to enumerate such questions, to learn what are the stronger warning signs when attempting to diagnose a disease, called Conditional Predictive Informativity, (CPI), whose ranking we call CPIR. This simple to use process allows us to identify particularly informative combinations of symptoms and traits that may help medical field analysis in general, and possibly to become a new data-driven advised approach for individual medical diagnosis, as well as for broader public policy discussion. In particular we have been motivated to develop this tool in the current environment of the pressing world crisis due to the COVID 19 pandemic. We apply the methods here to data collected from national, provincial, and municipal health reports, as well as additional information from online, and then curated to an online publically available Github repository.", "qid": 35, "docid": "5jwtykqg", "rank": 84, "score": 7.509698867797852}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 35, "docid": "h2tcrh1q", "rank": 85, "score": 7.472099781036377}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic. Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 35, "docid": "tfx7tx9i", "rank": 86, "score": 7.4720988273620605}, {"content": "Title: COVID-Net: A Tailored Deep Convolutional Neural Network Design for Detection of COVID-19 Cases from Chest X-Ray Images Content: The COVID-19 pandemic continues to have a devastating effect on the health and well-being of the global population. A critical step in the fight against COVID-19 is effective screening of infected patients, with one of the key screening approaches being radiology examination using chest radiography. Motivated by this and inspired by the open source efforts of the research community, in this study we introduce COVID-Net, a deep convolutional neural network design tailored for the detection of COVID-19 cases from chest X-ray (CXR) images that is open source and available to the general public. To the best of the authors' knowledge, COVID-Net is one of the first open source network designs for COVID-19 detection from CXR images at the time of initial release. We also introduce COVIDx, an open access benchmark dataset that we generated comprising of 13,975 CXR images across 13,870 patient patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge. Furthermore, we investigate how COVID-Net makes predictions using an explainability method in an attempt to not only gain deeper insights into critical factors associated with COVID cases, which can aid clinicians in improved screening, but also audit COVID-Net in a responsible and transparent manner to validate that it is making decisions based on relevant information from the CXR images. By no means a production-ready solution, the hope is that the open access COVID-Net, along with the description on constructing the open source COVIDx dataset, will be leveraged and build upon by both researchers and citizen data scientists alike to accelerate the development of highly accurate yet practical deep learning solutions for detecting COVID-19 cases and accelerate treatment of those who need it the most.", "qid": 35, "docid": "qb0s06tl", "rank": 87, "score": 7.466100215911865}, {"content": "Title: Open Access and Altmetrics in the pandemic age: Forescast analysis on COVID-19 literature Content: We present an analysis on the uptake of open access on COVID-19 related literature as well as the social media attention they gather when compared with non OA papers. We use a dataset of publications curated by Dimensions and analyze articles and preprints. Our sample includes 11,686 publications of which 67.5% are openly accessible. OA publications tend to receive the largest share of social media attention as measured by the Altmetric Attention Score. 37.6% of OA publications are bronze, which means toll journals are providing free access. MedRxiv contributes to 36.3% of documents in repositories but papers in BiorXiv exhibit on average higher AAS. We predict the growth of COVID-19 literature in the following 30 days estimating ARIMA models for the overall publications set, OA vs. non OA and by location of the document (repository vs. journal). We estimate that COVID-19 publications will double in the next 20 days, but non OA publications will grow at a higher rate than OA publications. We conclude by discussing the implications of such findings on the dissemination and communication of research findings to mitigate the coronavirus outbreak.", "qid": 35, "docid": "tudrm0k8", "rank": 88, "score": 7.4481000900268555}, {"content": "Title: Feature sensitivity criterion-based sampling strategy from the Optimization based on Phylogram Analysis (Fs-OPA) and Cox regression applied to mental disorder datasets Content: Digital datasets in several health care facilities, as hospitals and prehospital services, accumulated data from thousands of patients for more than a decade. In general, there is no local team with enough experts with the required different skills capable of analyzing them in entirety. The integration of those abilities usually demands a relatively long-period and is cost. Considering that scenario, this paper proposes a new Feature Sensitivity technique that can automatically deal with a large dataset. It uses a criterion-based sampling strategy from the Optimization based on Phylogram Analysis. Called FS-opa, the new approach seems proper for dealing with any types of raw data from health centers and manipulate their entire datasets. Besides, FS-opa can find the principal features for the construction of inference models without depending on expert knowledge of the problem domain. The selected features can be combined with usual statistical or machine learning methods to perform predictions. The new method can mine entire datasets from scratch. FS-opa was evaluated using a relatively large dataset from electronic health records of mental disorder prehospital services in Brazil. Cox's approach was integrated to FS-opa to generate survival analysis models related to the length of stay (LOS) in hospitals, assuming that it is a relevant aspect that can benefit estimates of the efficiency of hospitals and the quality of patient treatments. Since FS-opa can work with raw datasets, no knowledge from the problem domain was used to obtain the preliminary prediction models found. Results show that FS-opa succeeded in performing a feature sensitivity analysis using only the raw data available. In this way, FS-opa can find the principal features without bias of an inference model, since the proposed method does not use it. Moreover, the experiments show that FS-opa can provide models with a useful trade-off according to their representativeness and parsimony. It can benefit further analyses by experts since they can focus on aspects that benefit problem modeling.", "qid": 35, "docid": "dl7i8219", "rank": 89, "score": 7.439499855041504}, {"content": "Title: Feature sensitivity criterion-based sampling strategy from the Optimization based on Phylogram Analysis (Fs-OPA) and Cox regression applied to mental disorder datasets. Content: Digital datasets in several health care facilities, as hospitals and prehospital services, accumulated data from thousands of patients for more than a decade. In general, there is no local team with enough experts with the required different skills capable of analyzing them in entirety. The integration of those abilities usually demands a relatively long-period and is cost. Considering that scenario, this paper proposes a new Feature Sensitivity technique that can automatically deal with a large dataset. It uses a criterion-based sampling strategy from the Optimization based on Phylogram Analysis. Called FS-opa, the new approach seems proper for dealing with any types of raw data from health centers and manipulate their entire datasets. Besides, FS-opa can find the principal features for the construction of inference models without depending on expert knowledge of the problem domain. The selected features can be combined with usual statistical or machine learning methods to perform predictions. The new method can mine entire datasets from scratch. FS-opa was evaluated using a relatively large dataset from electronic health records of mental disorder prehospital services in Brazil. Cox's approach was integrated to FS-opa to generate survival analysis models related to the length of stay (LOS) in hospitals, assuming that it is a relevant aspect that can benefit estimates of the efficiency of hospitals and the quality of patient treatments. Since FS-opa can work with raw datasets, no knowledge from the problem domain was used to obtain the preliminary prediction models found. Results show that FS-opa succeeded in performing a feature sensitivity analysis using only the raw data available. In this way, FS-opa can find the principal features without bias of an inference model, since the proposed method does not use it. Moreover, the experiments show that FS-opa can provide models with a useful trade-off according to their representativeness and parsimony. It can benefit further analyses by experts since they can focus on aspects that benefit problem modeling.", "qid": 35, "docid": "hpeav816", "rank": 90, "score": 7.4394989013671875}, {"content": "Title: Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II): protocol for an observational study using linked Scottish national data Content: INTRODUCTION: Following the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 and the ensuing COVID-19 pandemic, population-level surveillance and rapid assessment of the effectiveness of existing or new therapeutic or preventive interventions are required to ensure that interventions are targeted to those at highest risk of serious illness or death from COVID-19. We aim to repurpose and expand an existing pandemic reporting platform to determine the attack rate of SARS-CoV-2, the uptake and effectiveness of any new pandemic vaccine (once available) and any protective effect conferred by existing or new antimicrobial drugs and other therapies. METHODS AND ANALYSIS: A prospective observational cohort will be used to monitor daily/weekly the progress of the COVID-19 epidemic and to evaluate the effectiveness of therapeutic interventions in approximately 5.4 million individuals registered in general practices across Scotland. A national linked dataset of patient-level primary care data, out-of-hours, hospitalisation, mortality and laboratory data will be assembled. The primary outcomes will measure association between: (A) laboratory confirmed SARS-CoV-2 infection, morbidity and mortality, and demographic, socioeconomic and clinical population characteristics; and (B) healthcare burden of COVID-19 and demographic, socioeconomic and clinical population characteristics. The secondary outcomes will estimate: (A) the uptake (for vaccines only); (B) effectiveness; and (C) safety of new or existing therapies, vaccines and antimicrobials against SARS-CoV-2 infection. The association between population characteristics and primary outcomes will be assessed via multivariate logistic regression models. The effectiveness of therapies, vaccines and antimicrobials will be assessed from time-dependent Cox models or Poisson regression models. Self-controlled study designs will be explored to estimate the risk of therapeutic and prophylactic-related adverse events. ETHICS AND DISSEMINATION: We obtained approval from the National Research Ethics Service Committee, Southeast Scotland 02. The study findings will be presented at international conferences and published in peer-reviewed journals.", "qid": 35, "docid": "rzla86sw", "rank": 91, "score": 7.418300151824951}, {"content": "Title: Comparative Global Epidemiological Investigation of SARS-CoV-2 and SARS-CoV Diseases Using Meta-MUMS Tool Through Incidence, Mortality, and Recovery Rates Content: COVID-19 is a novel coronavirus that was reported by the world health organization in late December 2019. As an unexplained respiratory disease epidemic, which is similar to respiratory syndrome coronavirus SARS-CoV, it rapidly spread all over the world. The study aims to compare several parameters of COVID-19 and SARS-CoV infectious diseases in terms of incidence, mortality, and recovery rates. The publicly available dataset Worldometer (extracted on April 5, 2020) confirmed by WHO report was available for meta-analysis purposes using the Meta-MUMS tool. And, the reported outcomes of the analysis used a random-effects model to evaluate the event rate, and risk ratios thorough subgroup analysis forest plots. Seventeen countries for COVID-19 and eight countries of SARS infections, including COVID-19 group n = 1124243, and SARS-CoV group n = 8346, were analyzed. In this meta-analysis, a random effect model of relations of incidence, mortality, and recovery rates of COVID-19 and SARS world infections were determined. The meta-analysis and forest plots of two viral world infections showed that the incidence rate of COVID-19 infection is more than SARS infections, while recovery and mortality event rates of SARS-CoV are more than COVID-19 infection. And subgroup analysis showed that the mortality and recovery rates were higher in both SARS-CoV wand COVID-19 in comparison to incidence and mortality rates, respectively. In conclusion, the meta-analysis approach on the abovementioned dataset revealed the epidemiological and statistical analyses for comparing COVID-19 and SARS-CoV outbreaks.", "qid": 35, "docid": "yx4g1l6d", "rank": 92, "score": 7.411399841308594}, {"content": "Title: iBioProVis: Interactive Visualization and Analysis of Compound Bioactivity Space. Content: SUMMARY iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs, and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2-D map, based on the similarity of structural properties of compounds and in the context of compounds' cognate targets. Similar compounds, which are embedded to proximate points on the 2-D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins' known ligands on the 2-D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on ACE2 protein which is SARS-CoV-2 Spike protein receptor. ACE2 binding compounds and 7 antiviral drugs were closely embedded in which two of them have been under clinical trial for COVID-19. AVAILABILITY AND IMPLEMENTATION iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.", "qid": 35, "docid": "5yc6u5t3", "rank": 93, "score": 7.405799865722656}, {"content": "Title: iBioProVis: Interactive Visualization and Analysis of Compound Bioactivity Space Content: SUMMARY: iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs, and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2-D map, based on the similarity of structural properties of compounds and in the context of compounds' cognate targets. Similar compounds, which are embedded to proximate points on the 2-D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins' known ligands on the 2-D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on ACE2 protein which is SARS-CoV-2 Spike protein receptor. ACE2 binding compounds and 7 antiviral drugs were closely embedded in which two of them have been under clinical trial for COVID-19. AVAILABILITY AND IMPLEMENTATION: iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "qid": 35, "docid": "jmiy97du", "rank": 94, "score": 7.40579891204834}, {"content": "Title: COVID-19 and Headache: A Primer for Trainees Content: OBJECTIVE: To summarize for the trainee audience the possible mechanisms of headache in patients with COVID-19 as well as to outline the impact of the pandemic on patients with headache disorders and headache medicine in clinical practice. BACKGROUND: COVID-19 is a global pandemic caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, of which a large subset of patients features neurological symptoms, commonly headache. The virus is highly contagious and is, therefore, changing clinical practice by forcing limitations on in-person visits and procedural treatments, more quickly shifting toward the widespread adaptation of telemedicine services. DESIGN/RESULTS: We review what is currently known about the pathophysiology of COVID-19 and how it relates to possible mechanisms of headache, including indirect, potential direct, and secondary causes. Alternative options for the treatment of patients with headache disorders and the use of telemedicine are also explored. CONCLUSIONS: Limited information exists regarding the mechanisms and timing of headache in patients with COVID-19, though causes relate to plausible direct viral invasion of the nervous system as well as the cytokine release syndrome. Though headache care in the COVID-19 era requires alterations, the improved preventive treatment options now available and evidence for feasibility and safety of telemedicine well positions clinicians to take care of such patients, especially in the COVID-19 epicenter of New York City.", "qid": 35, "docid": "kre0npli", "rank": 95, "score": 7.404600143432617}, {"content": "Title: New blood tests for antibodies could show true scale of coronavirus pandemic Content: How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease\u2014perhaps so mild they dismissed it as a cold or allergies\u2014immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests\u2014for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune\u2014is still lacking or at least not public Scientists hope that will soon change as more tests become available", "qid": 35, "docid": "ecxji8x8", "rank": 96, "score": 7.397799968719482}, {"content": "Title: CoroNet: A Deep Network Architecture for Semi-Supervised Task-Based Identification of COVID-19 from Chest X-ray Images Content: In late 2019, a new Coronavirus disease, referred to as Corona virus disease 2019 (COVID-19), emerged in Wuhan city, Hubei, China, and resulted in a global pandemic---claiming a large number of lives and affecting billions all around the world. The current global standard used in diagnosis of COVID-19 in suspected cases is the real-time polymerase chain reaction (RT-PCR) test. Although the RT-PCR remains the standard reference for diagnosis purposes, it is a time-consuming and expensive test, and moreover, it usually suffers from high rates of false-negatives. Several early works have reported that the sensitivity of the chest Computed Tomography (CT) and the chest X-ray imaging are noticeably greater than that of the RT-PCR test at the initial representations of the disease, making them great candidates for developing new and sophisticated methodologies for analysis and classification of COVID-19 cases. In this paper, we establish the use of a rapid, non-invasive and cost-effective X-ray-based method as a key diagnosis and screening tool for COVID-19 at early and intermediate stages of the disease. To this end, we develop a novel and sophisticated deep learning-based signal and image processing technique as well as classification methodology for analyzing X-ray images specific to COVID-19 disease. Specifically, we consider a semi-supervised learning methodology based on AutoEncoders to first extract the infected legions in chest X-ray manifestation of COVID-19 and other Pneumonia-like diseases (as well as healthy cases). Then, we utilize this highly-tailored deep architecture to extract the relevant features specific to each class (i.e., healthy, non-COVID pneumonia, and COVID-19) and train a powerful yet efficient classifier to perform the task of automatic diagnosis. Furthermore, the semi-supervised nature of the proposed framework enables us to efficiently exploit the limited available dataset on COVID-19 while exploiting the vast amount of available X-ray dataset for healthy and non-COVID classes. Moreover, such a semi-supervised approach does not require an expert-annotated lesion area for each class. Our numerical investigations demonstrate that the proposed framework outperforms the state-of-the-art methods for COVID-19 identification while employing approximately ten times fewer training parameters as compared to other existing methodologies for classification of the COVID-19 from X-ray images (facilitating efficient training in a limited data regime). We further develop explainable artificial intelligence tools that can explain the diagnosis by using attribution maps while providing an indispensable tool for the radiologist in triage state. We have made the codes of our proposed framework publicly available to the research and healthcare community.", "qid": 35, "docid": "qw5ly6rl", "rank": 97, "score": 7.3719000816345215}, {"content": "Title: Mapping the South African health landscape in response to COVID-19 Content: When the COVID-19 disease pandemic infiltrated the world, there was an immediate need for accurate information. As with any outbreak, the outbreak follows a clear trajectory, and subsequently, the supporting information for that outbreak needs to address the needs associated with that stage of the outbreak. At first, there was a need to inform the public of the information related to the initial situation related to the\"who\"of the COVID-19 disease. However, as time continued, the\"where\",\"when\"and\"how to\"related questions started to emerge in relation to the public healthcare system themselves. Questions surrounding the health facilities including COVID-19 hospital bed capacity, locations of designated COVID-19 facilities, and general information related to these facilities were not easily accessible to the general public. Furthermore, the available information was found to be outdated, fragmented across several platforms, and still had gaps in the data related to these facilities. To rectify this problem, a group of volunteers working on the covid19za project stepped in to assist. Each member leading a part of the project chose to focus on one of four problems related to the challenges associated with the Hospital information including: data quality, data completeness, data source validation and data visualisation capacity. As the project developed, so did the sophistication of the data, visualisation and core function of the project. The future prospects of this project relate to a Progressive Web Application that will avail this information for the public as well as healthcare workers through comprehensive mapping and data quality.", "qid": 35, "docid": "paoehsob", "rank": 98, "score": 7.367400169372559}, {"content": "Title: What Is Required to Prevent a Second Major Outbreak of SARS-CoV-2 upon Lifting Quarantine in Wuhan City, China Content: Summary Background The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Methods We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases in late April 2020. At the end of the epidemic, 65,733 (45,722-99,015) individuals would be infected by the virus, among which 16,166 (11,238-24,603, 24.6%) were through public contacts, 45,996 (31,892-69,565, 69.7%) through household contact, and 3,571 (2,521-5,879, 5.5%) through hospital contacts (including 778 (553-1,154) non-COVID-19 patients and 2,786 (1,969-4,791) medical staff). A total of 2,821 (1,634-6,361) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21st March is viable only if Wuhan residents sustain a high facial mask usage of \u226585% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to \u226575% at the same contact rate. Conclusions The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.", "qid": 35, "docid": "brt7ud3u", "rank": 99, "score": 7.365200042724609}, {"content": "Title: Modeling the Spread of COVID-19 Infection Using a Multilayer Perceptron Content: Coronavirus (COVID-19) is a highly infectious disease that has captured the attention of the worldwide public. Modeling of such diseases can be extremely important in the prediction of their impact. While classic, statistical, modeling can provide satisfactory models, it can also fail to comprehend the intricacies contained within the data. In this paper, authors use a publicly available dataset, containing information on infected, recovered, and deceased patients in 406 locations over 51 days (22nd January 2020 to 12th March 2020). This dataset, intended to be a time-series dataset, is transformed into a regression dataset and used in training a multilayer perceptron (MLP) artificial neural network (ANN). The aim of training is to achieve a worldwide model of the maximal number of patients across all locations in each time unit. Hyperparameters of the MLP are varied using a grid search algorithm, with a total of 5376 hyperparameter combinations. Using those combinations, a total of 48384 ANNs are trained (16128 for each patient group-deceased, recovered, and infected), and each model is evaluated using the coefficient of determination (R2). Cross-validation is performed using K-fold algorithm with 5-folds. Best models achieved consists of 4 hidden layers with 4 neurons in each of those layers, and use a ReLU activation function, with R2 scores of 0.98599 for confirmed, 0.99429 for deceased, and 0.97941 for recovered patient models. When cross-validation is performed, these scores drop to 0.94 for confirmed, 0.781 for recovered, and 0.986 for deceased patient models, showing high robustness of the deceased patient model, good robustness for confirmed, and low robustness for recovered patient model.", "qid": 35, "docid": "0u14d9j1", "rank": 100, "score": 7.362400054931641}]}
{"query": "What is the protein structure of the SARS-CoV-2 spike?", "hits": [{"content": "Title: Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2 Content: Abstract What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged \u03b2 coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The spike, nucleocapsid, membrane, and envelope proteins are structural proteins. The S1 subunit of spike protein facilitates ACE2 mediated virus attachment and S2 subunit for membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino in SARS-CoV-2 enhanced ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N terminal (NTD) and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. Envelope proteins contain an NTD, hydrophobic domain and C terminal which form viroporins needed for viral assembly. Membrane proteins hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and interaction with E facilitate virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.", "qid": 36, "docid": "7axo7k51", "rank": 1, "score": 13.3371000289917}, {"content": "Title: Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2 Content: What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged \u00df coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The structural proteins include spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S1 subunit of S protein facilitates ACE2 mediated virus attachment while S2 subunit promotes membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino acids in SARS-CoV-2 enhances ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N Terminal Domain (NTD) and C Terminal Domain (CTD). These terminals play a role in viral entry and its processing post entry. The NTD forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. The E protein contains a NTD, hydrophobic domain and CTD which form viroporins needed for viral assembly. The M protein possesses hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and the interaction with E facilitates virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.", "qid": 36, "docid": "9sbrxzxu", "rank": 2, "score": 12.859299659729004}, {"content": "Title: Structural Basis of SARS-CoV-2 Spike Protein Priming by TMPRSS2 Content: Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational details of complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike and to point candidate drug targets. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provide structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.", "qid": 36, "docid": "34ljq0qt", "rank": 3, "score": 12.678500175476074}, {"content": "Title: Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein Content: The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.", "qid": 36, "docid": "4nfxdppt", "rank": 4, "score": 12.497699737548828}, {"content": "Title: Structural variations in human ACE2 may influence its binding with SARS\u2010CoV\u20102 spike protein Content: The recent pandemic of COVID\u201019, caused by SARS\u2010CoV\u20102, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS\u2010CoV and MERS\u2010CoV. Human ACE2 is now established as a receptor for the SARS\u2010CoV\u20102 spike protein. Where variations in the viral spike protein, in turn, lead to the cross\u2010species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS\u2010CoV\u20102 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2\u2010spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS\u2010CoV\u20102 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild\u2010type molecule. Most ACE2 variants showed a similar binding affinity for SARS\u2010CoV\u20102 spike protein as observed in the complex structure of wild\u2010type ACE2 and SARS\u2010CoV\u20102 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS\u2010CoV\u20102 infection driven by ACE2 allelic variants.", "qid": 36, "docid": "m0w0fl2u", "rank": 5, "score": 12.497698783874512}, {"content": "Title: N-glycosylation network construction and analysis to modify glycans on the spike S glycoprotein of SARS-CoV-2 Content: Background The spike S-protein of SARS-CoV-2 is N-glycosylated. The N-glycan structure and composition of this glycoprotein influence how the virus interacts with host cells. Objective To identify a putative N-glycan biosynthesis pathway of SARS-CoV-2 (HEK293 cell recombinant) from previously published mass spectrometric studies, and to identify what effect blocking some enzymes has on the overall glycoprotein profile. Finally, our goal was to provide the biosynthesis network, and glycans in easy-to-use format for further glycoinformatics work. Methods We reconstructed the glycosylation network based on previously published empirical data using GNAT, a glycosylation network analysis tool. Our compilation of the network tool had 23 glycosyltransferase and glucosidase enzymes, and could infer the pathway of glycosylation machinery based on glycans identified in the virus spike protein. Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes - Mannosidase-II and alpha-1,6-fucosyltransferase to see how they would affect the biosynthesis network. Results Of the 23 enzymes, a total of 12 were involved in glycosylation of SARS-CoV-2 - Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B4GalT, B4GalT, Man II, SiaT, ST3GalI, ST3GalVI and FucT8. Blocking enzymes resulted in a substantially modified glycan profile of the protein. Conclusions A network analysis of N-glycan biosynthesis of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies. Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, could be a factor in the host response to the infection and response to antibodies. Here we provide all the resources generated - the glycans derived from mass spectrometry and intermediate glycans in glycoCT xml format, and the biosynthesis network for future drug and vaccine development work.", "qid": 36, "docid": "mrepq17b", "rank": 6, "score": 11.973199844360352}, {"content": "Title: Adding the missing sugars to coronavirus protein structures Content: Protein structures solved by cryo-electron microscopy (cryo-EM) or X-ray crystallography often miss the sugar molecules known as glycans that cover large swaths of the proteins\u2019 surfaces The recently reported structures of the spike protein on SARS-CoV-2, the novel coronavirus that causes COVID-19, are no different Researchers are now working to fill in some of those sugary blanks to better understand the virus\u2019s biology and to help drugmakers develop vaccines and treatments \u201cPeople usually go for what they can analyze\u201d and focus mostly on the protein components of a structure, says Andrea Thorn, a structural biologist at the Julius Maximilian University of W\u00fcrzburg She is a member of the Coronavirus Structural Task Force, a group of scientists who specialize in modeling and processing crystallographic and cryo-EM data Because structural biology measurements don\u2019t reveal much about glycans on proteins, \u201cwe often fail to recognize what an important part of the structure they", "qid": 36, "docid": "fayr38c7", "rank": 7, "score": 11.859100341796875}, {"content": "Title: N and O glycosylation of the SARS-CoV-2 spike protein Content: Covid-19 pandemic outbreak is the reason of the current world health crisis. The development of effective antiviral compounds and vaccines requires detailed descriptive studies of the SARS-CoV-2 proteins. The SARS-CoV-2 spike (S) protein mediates virion binding to the human cells through its interaction with the ACE2 cell surface receptor and is one of the prime immunization targets. A functional virion is composed of three S1 and three S2 subunits created by furin cleavage of the spike protein at R682, a polybasic cleavage sites that differs from the SARS-CoV spike protein of 2002. We observe that the spike protein is O-glycosylated on a threonine (T678) near the furin cleavage site occupied by core-1 and core-2 structures. In addition, we have identified eight additional O-glycopeptides on the spike glycoprotein and we confirmed that the spike protein is heavily N-glycosylated. Our recently developed LC-MS/MS methodology allowed us to identify LacdiNAc structural motifs on all occupied N-glycopeptides and polyLacNAc structures on six glycopeptides of the spike protein. In conclusion, our study substantially expands the current knowledge of the spike protein\u2019s glycosylation and enables the investigation of the influence of the O-glycosylation on its proteolytic activation.", "qid": 36, "docid": "ssffvlrl", "rank": 8, "score": 11.853099822998047}, {"content": "Title: Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. Content: The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called Covid-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be 'preactivated' and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.", "qid": 36, "docid": "40ejbv5j", "rank": 9, "score": 11.839900016784668}, {"content": "Title: Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein Content: The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be 'preactivated' and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.", "qid": 36, "docid": "50hqr249", "rank": 10, "score": 11.839899063110352}, {"content": "Title: Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes Content: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 \u00c5-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.", "qid": 36, "docid": "g81ylcxq", "rank": 11, "score": 11.788900375366211}, {"content": "Title: Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein Content: The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 7,000,000 infections and 400,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARSCoV-2 spike (S) protein, which mediates the host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). In the context of vaccine design, similar to many other viruses, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the glycan shield and the protein structure, stability, and dynamics. End-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of SARS-CoV-2 S protein, which can be harnessed for vaccine development. In addition, a dynamic analysis of the main antibody epitopes is provided. Finally, beyond shielding, a possible structural role of N-glycans at N165 and N234 is hypothesized to modulate and stabilize the conformational dynamics of the spike\u2019s receptor binding domain, which is responsible for ACE2 recognition. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, which may be exploited by therapeutic efforts targeting this essential molecular machine.", "qid": 36, "docid": "1c1k0p93", "rank": 12, "score": 11.693699836730957}, {"content": "Title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach Content: SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.", "qid": 36, "docid": "53mu0702", "rank": 13, "score": 11.673100471496582}, {"content": "Title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach Content: [Image: see text] SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.", "qid": 36, "docid": "xy8j5jiv", "rank": 14, "score": 11.673099517822266}, {"content": "Title: Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition Content: Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain \"MESEFR\" and \"SYLTPG\" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions \"VGGNY\" and \"EIYQAGSTPCNGV\" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.", "qid": 36, "docid": "n9rwixr4", "rank": 15, "score": 11.65310001373291}, {"content": "Title: CoV3D: A database of high resolution coronavirus protein structures Content: The SARS-CoV-2 virus is the cause of the current COVID-19 pandemic, and exemplifies the general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal a map of virus vulnerabilities. To assist structure-based design of vaccines and therapeutics against SARS-CoV-2 and other coronaviruses, we developed CoV3D, a database and molecular viewer of SARS-CoV-2 and other coronavirus protein structures updated weekly. CoV3D annotates structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Additionally, CoV3D provides information on spike glycoprotein sequence variability and polymorphisms, and maps these features onto the spike structure in the integrated molecular viewer. In order to further aid structure-based design and analysis, CoV3D includes viewable and downloadable spike glycoprotein structures with modeled glycosylation from Rosetta. CoV3D is available at: https://cov3d.ibbr.umd.edu.", "qid": 36, "docid": "co27h1kj", "rank": 16, "score": 11.642600059509277}, {"content": "Title: Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December 2019, is a novel virus that causes a severe acute respiratory disease. The virus spike glycoproteins and nucleocapsid proteins are the main targets for the development of vaccines and antiviral drugs, to control the disease spread. We herein study the structural order-disorder propensity and the rates of evolution of these two proteins to characterize their B cell and T cell epitopes, previously suggested to contribute to immune response caused by SARS-CoV-2 infections. We first analyzed the rates of evolution along the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes. For this purpose, we compared orthologs from seven human coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. We then focus on the local, structural order-disorder propensities of the protein regions where the SARS-CoV-2 epitopes are located. We show that the vast majority of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains and some of them are characterized by low rates of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well-conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by high rates of evolution, probably to overcome host immunity. In conclusion, our results provide evidence for conserved epitopes that may help to develop long-lasting, broad-spectrum SARS-CoV-2 vaccines.", "qid": 36, "docid": "lg7nnmb6", "rank": 17, "score": 11.619099617004395}, {"content": "Title: Evolutionary relationships and sequence\u2010structure determinants in human SARS coronavirus\u20102 spike proteins for host receptor recognition Content: Coronavirus disease 2019 (COVID\u201019) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus\u20102 (SARS CoV\u20102). The SARS CoV\u20102 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV\u20102 via their glycosylated spike proteins recognize the human angiotensin converting enzyme\u20102 (ACE\u20102) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV\u20102 from various host sources in order to analyze the specificity in SARS CoV\u20102 spike proteins required for causing infection in humans. Our results show that among the genomes analysed, two sequence regions in the N\u2010terminal domain (NTD); \"MESEFR\" and \"SYLTPG\" are specific to human SARS CoV\u20102. In the receptor binding domain (RBD), two sequence regions; \"VGGNY\" and \"EIYQAGSTPCNGV\" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE\u20102 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources and human SARS CoV\u20102 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV\u20102 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV\u20102. This article is protected by copyright. All rights reserved.", "qid": 36, "docid": "1dxu14b1", "rank": 18, "score": 11.565099716186523}, {"content": "Title: SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein Content: The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.", "qid": 36, "docid": "srgi9jc6", "rank": 19, "score": 11.555299758911133}, {"content": "Title: A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies Content: The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 \u00c5 resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design. Highlights Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike. 3.1 \u00c5 resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12. 2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike. Our studies suggest a common epitope for FDG antibodies centered around glycan 709.", "qid": 36, "docid": "nq16jcs9", "rank": 20, "score": 11.524999618530273}, {"content": "Title: Differential Antibody Recognition by Novel SARS-CoV-2 and SARS-CoV Spike Protein Receptor Binding Domains: Mechanistic Insights and Implications for the Design of Diagnostics and Therapeutics Content: The appearance of the novel betacoronavirus SARS-CoV-2 represents a major threat to human health, and its diffusion around the world is causing dramatic consequences. The knowledge of the 3D structures of SARS-CoV-2 proteins can facilitate the development of therapeutic and diagnostic molecules. Specifically, comparative analyses of the structures of SARS-CoV-2 proteins and homologous proteins from previously characterized viruses, such as SARS-CoV, can reveal the common and/or distinctive traits that underlie the mechanisms of recognition of cell receptors and of molecules of the immune system. Herein, we apply our recently developed energy-based methods for the prediction of antibody-binding epitopes and protein-protein interaction regions to the Receptor Binding Domain (RBD) of the Spike proteins from SARS-CoV-2 and SARS-CoV. Our analysis focusses only on the study of the structure of RBDs in isolation, without making use of any previous knowledge of binding properties. Importantly, our results highlight structural and sequence differences among the regions that are predicted to be immunoreactive and bind/elicit antibodies. These results provide a rational basis to the observation that several SARS-CoV RDB-specific monoclonal antibodies fail to appreciably bind the SARS-CoV-2 counterpart. Furthermore, we correctly identify the region of SARS-CoV-2 RBD that is engaged by the cell receptor ACE2 during viral entry into host cells. The data, sequences and structures we present here can be useful for the development of novel therapeutic and diagnostic interventions.", "qid": 36, "docid": "c08ptb1o", "rank": 21, "score": 11.510499954223633}, {"content": "Title: Considerations around the SARS-CoV-2 Spike Protein with particular attention to COVID-19 brain infection and neurological symptoms. Content: Spike protein (S protein) is the virus 'key' to infect cells being able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as it has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very few evidence have been so far reported on the presence of COVID-19 in the brain and the potential exploitation, by this virus, of lung to brain axis to reach neurons has not completely understood. In this article we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through non-specific and specific interactions. Analyzing of the S protein binds to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood brain barrier crossing and clinical features related to the CNS infection by SARS-CoV-2.", "qid": 36, "docid": "2bz78yl1", "rank": 22, "score": 11.461299896240234}, {"content": "Title: Considerations around the SARS-CoV-2 Spike Protein with particular attention to COVID-19 brain infection and neurological symptoms Content: Spike protein (S protein) is the virus 'key' to infect cells being able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as it has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very few evidence have been so far reported on the presence of COVID-19 in the brain and the potential exploitation, by this virus, of lung to brain axis to reach neurons has not completely understood. In this article we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through non-specific and specific interactions. Analyzing of the S protein binds to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood brain barrier crossing and clinical features related to the CNS infection by SARS-CoV-2.", "qid": 36, "docid": "t4bqmgcl", "rank": 23, "score": 11.461298942565918}, {"content": "Title: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations Content: Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 \u00b0C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 \u00b0C and attains a completely closed conformation at 50 \u00b0C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract Highlights Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike\u2019s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30\u00b0 C. The Receptor Binding Motif adopts a closed conformation at 40\u00b0C and completely closes at higher temperatures making it unsuitable of binding to human receptors", "qid": 36, "docid": "nsp53lv6", "rank": 24, "score": 11.446200370788574}, {"content": "Title: Structural interactions between pandemic SARS-CoV-2 spike glycoprotein and human Furin protease Content: The SARS-CoV-2 pandemic is an urgent global public health emergency and warrants investigating molecular and structural studies addressing the dynamics of viral proteins involved in host cell adhesion. The recent comparative genomic studies highlight the insertion of Furin protease site in the SARS-CoV-2 spike glycoprotein alerting possible modification in the viral spike protein and its eventual entry to host cell and presence of Furin site implicated to virulence. Here we structurally show how Furin interacts with the SARS-CoV-2 spike glycoprotein homotrimer at S1/S2 region, which underlined the mechanism and mode of action, which is a key for host cell entry. Unravelling the structural features of biding site opens the arena in rising bonafide antibodies targeting to block the Furin cleavage and have great implications in the development of Furin inhibitors or therapeutics.", "qid": 36, "docid": "uuws2nen", "rank": 25, "score": 11.438300132751465}, {"content": "Title: An engineered stable mini-protein to plug SARS-Cov-2 Spikes Content: The novel betacoronavirus SARS-CoV-2 is the etiological agent of the current pandemic COVID-19. Like other coronaviruses, this novel virus relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2 have a great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 Spike protein and the host ACE2 receptor, we here engineered a mini-protein with the aim of creating a soluble and stable Spike interactor. This mini-protein, which was recombinantly produced in high yields, possesses a stable \u03b1 helical conformation and is able to interact with the RBD of glycosylated Spike protein from SARS-CoV-2 with nanomolar affinity, as measured by microscale thermophoresis. By plugging the Spike protein, our mini-protein constitutes a valid tool for the development of treatments against different types of coronavirus.", "qid": 36, "docid": "5ftpxlfe", "rank": 26, "score": 11.419099807739258}, {"content": "Title: Delving deep into the structural aspects of a furin cleavage site inserted into the spike protein of SARS-CoV-2: A structural biophysical perspective Content: One notable feature of the SARS-CoV-2 genome, the spike (S) protein of SARS-CoV-2 has a polybasic furin cleavage site (FCS) at its S1-S2 boundary through the insertion of 12 nucleotides encoding four amino acid residues PRRA. Quite intriguingly, this polybasic FCS is absent in coronaviruses of the same clade as SARS-CoV-2. Thus, with currently available experimental structural data for S protein, this short article presents a set of comprehensive structural characterization of the insertion of FCS into S protein, and argues against a hypothesis of the origin of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS is spatially located at a random coil loop region, mostly distantly solvent-exposed (instead of deeply buried), with no structural proximity to the other part of the S protein; (2), the insertion of FCS itself does not alter, neither stabilize nor de-stabilize, the three-dimensional structure of S; (3), the net result here is the insertion of a furin cleavage site into S protein, whose S1 and S2 subunits will still be strongly electrostatically bonded together from a structural and biophysical point of view, even if the polybasic FCS is actually cleaved by furin protease before or after viral cell entry.", "qid": 36, "docid": "30bc6f4r", "rank": 27, "score": 11.410300254821777}, {"content": "Title: Structure, function and variants analysis of the androgen-regulated TMPRSS2, a drug target candidate for COVID-19 infection Content: SARS-CoV-2 is a novel virus causing mainly respiratory, but also gastrointestinal symptoms. Elucidating the molecular processes underlying SARS-CoV-2 infection, and how the genetic background of an individual is responsible for the variability in clinical presentation and severity of COVID-19 is essential in understanding this disease. Cell infection by the SARS-CoV-2 virus requires binding of its Spike (S) protein to the ACE2 cell surface protein and priming of the S by the serine protease TMPRSS2. One may expect that genetic variants leading to a defective TMPRSS2 protein can affect SARS-CoV-2 ability to infect cells. We used a range of bioinformatics methods to estimate the prevalence and pathogenicity of TMPRSS2 genetic variants in the human population, and assess whether TMPRSS2 and ACE2 are co-expressed in the intestine, similarly to what is observed in lungs. We generated a 3D structural model of the TMPRSS2 extracellular domain using the prediction server Phyre and studied 378 naturally-occurring TMPRSS2 variants reported in the GnomAD database. One common variant, p.V160M (rs12329760), is predicted damaging by both SIFT and PolyPhen2 and has a MAF of 0.25. Valine 160 is a highly conserved residue within the SRCS domain. The SRCS is found in proteins involved in host defence, such as CD5 and CD6, but its role in TMPRSS2 remains unknown. 84 rare variants (53 missense and 31 leading to a prematurely truncated protein, cumulative minor allele frequency (MAF) 7.34\u00d710\u22124) cause structural destabilization and possibly protein misfolding, and are also predicted damaging by SIFT and PolyPhen2 prediction tools. Moreover, we extracted gene expression data from the human protein atlas and showed that both ACE2 and TMPRSS2 are expressed in the small intestine, duodenum and colon, as well as the kidneys and gallbladder. The implications of our study are that: i. TMPRSS2 variants, in particular p.V160M with a MAF of 0.25, should be investigated as a possible marker of disease severity and prognosis in COVID-19 and ii. in vitro validation of the co-expression of TMPRSS2 and ACE2 in gastro-intestinal is warranted.", "qid": 36, "docid": "lvqwszsf", "rank": 28, "score": 11.310199737548828}, {"content": "Title: Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Content: SARS-CoV-2 is a single-stranded RNA virus of ~30 kb genome size which belongs to genus Coronavirus and family Coronaviridae. SARS-CoV-2 has recently emerged and has been declared as a pandemic by the World Health Organization. Genomic characterization of SARS-CoV-2 has shown that it is of zoonotic origin. The structure of SARS-CoV-2 is found to be similar to SARS-CoV with virion size ranging from 70 to 90 nm. Spike, membrane, and envelope surface viral proteins of coronavirus are embedded in host membrane-derived lipid bilayer encapsulating the helical nucleocapsid comprising viral RNA. The genome comprises of 6\u201311 open reading frames (ORFs) with 5\u2032 and 3\u2032 flanking untranslated regions (UTRs). Sequence variation among SARS-CoV-2 and SARS-CoV revealed no significant difference in ORFs and nsps. The nsps includes two viral cysteine proteases including papain-like protease (nsp3), chymotrypsin-like, 3C-like, or main protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), and others likely to be involved in the transcription and replication of SARS-CoV-2. The structure of spike glycoprotein structure of SARS-CoV-2 resembles that of the spike protein of SARS-CoV with an root-mean-square deviation (RMSD) of 3.8 \u00c5. Like SARS-CoV, SARS-CoV-2 uses the ACE2 receptor for internalization and TMPRSS2 serine proteases for S protein priming. Histopathological investigation of tissues from SARS-CoV-2 infected patients showed virus-induced cytopathic effect with signs of acute respiratory distress syndrome in lung cells. This chapter discusses about the morphology, genome organization, replication, and pathogenesis of SARS-CoV-2 that may help us understand the disease that may leads to identification of effective antiviral drugs and vaccines.", "qid": 36, "docid": "t0cw7l2a", "rank": 29, "score": 11.294599533081055}, {"content": "Title: Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein Content: A novel coronavirus (the SARS-CoV-2) has been identified in January 2020 as the causal pathogen for COVID-19 pneumonia, an outbreak started near the end of 2019 in Wuhan, China. The SARS-CoV-2 was found to be closely related to the SARS-CoV, based on the genomic analysis. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2 as well, initiated by the binding of the spike protein to the human ACE2. Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The predicted model is highly consistent with the experimentally determined complex structures. Plausible binding modes between human ACE2 and the RBD were revealed from all-atom MD simulations. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. Two mutants mimicking rat ACE2 were modeled to study the mutation effects on RBD binding to ACE2. The simulations showed that the N-terminal helix and the K353 of the human ACE2 alter the binding modes of the CoV2-RBD to the ACE2.", "qid": 36, "docid": "kifqgskc", "rank": 30, "score": 11.28600025177002}, {"content": "Title: Structural Molecular Insights into SARS Coronavirus Cellular Attachment, Entry and Morphogenesis Content: Coronavirus spikes have the largest mass of any known viral spike molecule. The spike is a type 1 viral fusion protein, a class of trimeric surface glycoprotein proteins from diverse viral families that share many common structural and functional characteristics. Fusion proteins are mainly responsible for host cell receptor recognition and subsequent membrane fusion, and may perform other roles such as virus assembly and release via budding. The conformational changes that occur in the spike of intact SARS coronavirus (SARS-CoV) when it binds to the viral receptor, angiotensin-converting enzyme 2 (ACE2) are described. Clues to the structural/functional relationships of membrane fusion have been made possible by the development of viral purification and inactivation methods, along with cryo-electron microscopy (cryo-EM) and three-dimensional (3D) image processing of many different images containing multiple views of the spikes. These methods have allowed study of the spikes while still attached to virions that are noninfectious, but fusionally competent. The receptor-binding and fusion core domains within the SARS-CoV spike have been precisely localized within the spike. Receptor binding results in structural changes that have been observed in the spike molecule, and these appear to be the initial step in viral membrane fusion. A working model for the stepwise process of receptor binding, and subsequent membrane fusion in SARS-CoV is presented. Uniquely, the large size of the SARS-CoV spike allows structural changes to be observed by cryo-EM in the native state. This provides a useful model for studying the basic process of membrane fusion in general, which forms an essential part of the function of many cellular processes.", "qid": 36, "docid": "w2sbyfy2", "rank": 31, "score": 11.269599914550781}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 36, "docid": "c5fygzvz", "rank": 32, "score": 11.268699645996094}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 36, "docid": "w5ytp1q7", "rank": 33, "score": 11.268698692321777}, {"content": "Title: Prefusion spike protein stabilization through computational mutagenesis Content: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines\u2019 developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants.", "qid": 36, "docid": "86hv27vh", "rank": 34, "score": 11.2391996383667}, {"content": "Title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets Content: The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.", "qid": 36, "docid": "klb8oe9q", "rank": 35, "score": 11.238900184631348}, {"content": "Title: SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects Content: SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "qid": 36, "docid": "3damlwoj", "rank": 36, "score": 11.214799880981445}, {"content": "Title: SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Content: SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "qid": 36, "docid": "guxbf60n", "rank": 37, "score": 11.214798927307129}, {"content": "Title: Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota Content: The immediate call for translational research in the field of coronavirus disease (COVID-19) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein with the host lung microbiota. Exploring solid-phase immunoassays, we evaluated the interactions between the SARS-CoV-2 spike protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike protein to the receptors DC-SIGN, MGL, Siglec-9 and Siglec-10 that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection, we studied the interactions between the SARS-CoV-2 spike protein and a library of Streptococcus pneumoniae capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein to different S. pneumoniae capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections and pneumonia. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike protein. In conclusion, we revealed novel ACE2-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glyco-conjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection and severity.", "qid": 36, "docid": "sfjrzq13", "rank": 38, "score": 11.211999893188477}, {"content": "Title: Structural basis of SARS-CoV-2 spike protein induced by ACE2 Content: Motivation The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. Results Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that \u03ba-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like \u03ba-helix and \u03b2-strand, and conformational variations in a set of short \u03b1-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.", "qid": 36, "docid": "yfn9vaan", "rank": 39, "score": 11.200599670410156}, {"content": "Title: Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide Content: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "qid": 36, "docid": "zu46bdpu", "rank": 40, "score": 11.177399635314941}, {"content": "Title: The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.", "qid": 36, "docid": "4skamxby", "rank": 41, "score": 11.163800239562988}, {"content": "Title: The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding Content: The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection. TOC: The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites", "qid": 36, "docid": "z7fgmpc5", "rank": 42, "score": 11.161700248718262}, {"content": "Title: Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient Content: The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6\u00c5 crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.", "qid": 36, "docid": "welf0eb1", "rank": 43, "score": 11.155200004577637}, {"content": "Title: Dynamics of the ACE2 - SARS-CoV/SARS-CoV-2 spike protein interface reveal unique mechanisms Content: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major public health concern. A handful of static structures now provide molecular insights into how SARS-CoV-2 and SARS-CoV interact with its host target, which is the angiotensin converting enzyme 2 (ACE2). Molecular recognition, binding and function are dynamic processes. To evaluate this, multiple all atom molecular dynamics simulations of at least 500 ns each were performed to better understand the structural stability and interfacial interactions between the receptor binding domain of the spike protein of SARS-CoV-2 and SARS-CoV bound to ACE2. Several contacts were observed to form, break and reform in the interface during the simulations. Our results indicate that SARS-CoV and SARS-CoV-2 utilizes unique strategies to achieve stable binding to ACE2. Several differences were observed between the residues of SARS-CoV-2 and SARS-CoV that consistently interacted with ACE2. Notably, a stable salt bridge between Lys417 of SARS-CoV-2 spike protein and Asp30 of ACE2 as well as three stable hydrogen bonds between Tyr449, Gln493, and Gln498 of SARS-CoV-2 and Asp38, Glu35, and Lys353 of ACE2 were observed, which were absent in the SARS-CoV-ACE2 interface. Some previously reported residues, which were suggested to enhance the binding affinity of SARS-CoV-2, were not observed to form stable interactions in these simulations. Stable binding to the host receptor is crucial for virus entry. Therefore, special consideration should be given to these stable interactions while designing potential drugs and treatment modalities to target or disrupt this interface.", "qid": 36, "docid": "5ach9vnk", "rank": 44, "score": 11.135899543762207}, {"content": "Title: Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies Content: The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using the bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS-CoV-1, and is highly conserved in the N-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds. Additionally, two distinct \u201ccore\u201d structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for LAV development and generating therapeutic interventions against the virus. Significance Statement Structural modeling of the novel SARS-CoV-2 envelope protein (E-protein) demonstrating its possible proton channeling activity", "qid": 36, "docid": "2f1c6h4q", "rank": 45, "score": 11.091099739074707}, {"content": "Title: Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state. Content: The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.", "qid": 36, "docid": "jfq7820g", "rank": 46, "score": 11.088600158691406}, {"content": "Title: Antigenic evolution on global scale reveals potential natural selection of SARS-CoV-2 by pre-existing cross-reactive T cell immunity Content: The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is constantly changing with the places of transmission, but the reason remains to be revealed. Here, we presented the study that comprehensively analyzed the potential selective pressure of immune system restriction, which can drive mutations in circulating SARS-CoV-2 isolates. The results showed that the most common mutation sites of SARS-CoV-2 proteins were located on the non-structural protein ORF1ab and the structural protein Spike. Further analysis revealed mutations in cross-reactive epitopes between SARS-CoV-2 and seasonal coronavirus may help SARS-CoV-2 to escape cellular immunity under the long-term and large-scale community transmission. Meanwhile, the mutations on Spike protein may enhance the ability of SARS-CoV-2 to enter the host cells and escape the recognition of B-cell immunity. This study will increase the understanding of the evolutionary direction and warn about the potential immune escape ability of SARS-CoV-2, which may provide important guidance for the potential vaccine design.", "qid": 36, "docid": "yop76n7z", "rank": 47, "score": 11.057299613952637}, {"content": "Title: Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein Content: COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2. One Sentence Summary A direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.", "qid": 36, "docid": "yjsxen4d", "rank": 48, "score": 11.055899620056152}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.", "qid": 36, "docid": "zso57yi7", "rank": 49, "score": 11.012100219726562}, {"content": "Title: Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination Content: Various human pathogenic viruses employ envelope glycoproteins for host cell receptor recognition and binding, membrane fusion and viral entry. The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion. The S protein is densely decorated with N-linked glycans protruding from the trimer surface that affect S protein folding, processing by host cell proteases and the elicitation of humoral immune response. Deep insight into the sophisticated structure of SARS-CoV-2 S protein may provide a blueprint for vaccination strategies, as reviewed herein.", "qid": 36, "docid": "ust578fc", "rank": 50, "score": 11.010000228881836}, {"content": "Title: SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development Content: SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses\u2019 similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.", "qid": 36, "docid": "nhq0oq8y", "rank": 51, "score": 10.994400024414062}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.", "qid": 36, "docid": "mswmkgl4", "rank": 52, "score": 10.994199752807617}, {"content": "Title: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity Content: The spike (S) glycoprotein of SARS-CoV-2 is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18,354 mutations in S protein were analyzed and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3,705 mutations in SARS-CoV-2 RBD and 11,324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.", "qid": 36, "docid": "jty4ebdf", "rank": 53, "score": 10.991399765014648}, {"content": "Title: Controlling the SARS-CoV-2 Spike Glycoprotein Conformation Content: The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available \u03b2-CoV S-protein structures. We found that despite overall similarity in domain organization, different \u03b2-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs \u2018down\u2019 position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs \u2018up\u2019 configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications.", "qid": 36, "docid": "yl6seuht", "rank": 54, "score": 10.989500045776367}, {"content": "Title: A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.", "qid": 36, "docid": "b3l4sy1u", "rank": 55, "score": 10.98840045928955}, {"content": "Title: From SARS and MERS CoVs to SARS\u2010CoV\u20102: Moving toward more biased codon usage in viral structural and nonstructural genes Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS\u2010CoV\u20102 and the changes in SARS\u2010CoV\u20102 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA\u2010dependent RNA polymerase and main protease (Mpro) of SARS\u2010CoV\u20102, Beta\u2010CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS\u2010CoV\u20102 prefers pyrimidine rich codons to purines. Most high\u2010frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS\u2010CoV\u20102 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS\u2010CoV\u20102 structural proteins. SARS\u2010CoV\u20102 encoded the highest number of over\u2010biased and negatively biased codons. Pangolin Beta\u2010CoV showed little differences with SARS\u2010CoV\u20102 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS\u2010CoV\u20102, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.", "qid": 36, "docid": "4jky78sl", "rank": 56, "score": 10.967100143432617}, {"content": "Title: From SARS and MERS CoVs to SARS-CoV-2: Moving toward more biased codon usage in viral structural and nonstructural genes Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA-dependent RNA polymerase and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over-biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.", "qid": 36, "docid": "oxxrnw1r", "rank": 57, "score": 10.9670991897583}, {"content": "Title: Role of the GTNGTKR motif in the N-terminal receptor-binding domain of the SARS-CoV-2 spike protein Content: The 2019 novel coronavirus disease (COVID-19) that emerged in China has been declared as public health emergency of international concern by the World Health Organization and the causative pathogen was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, we analyzed the structural characteristics of the N-terminal domain of the S1 subunit (S1-NTD) of the SARS-CoV-2 spike protein in comparison to the SARS-CoV in particular, and to other viruses presenting similar characteristic in general. Given the severity and the wide and rapid spread of the SARS-CoV-2 infection, it is very likely that the virus recognizes other receptors/co-receptors besides the ACE2. The NTD of the SARS-CoV-2 contains a receptor-binding motif different from that of SARS-CoV, with some insertions that could confer to the new coronavirus new receptor binding abilities. In particular, motifs similar to the insertion 72GTNGTKR78 have been found in structural proteins of other viruses; and these motifs were located in putative regions involved in recognizing protein and sugar receptors, suggesting therefore that similar binding abilities could be displayed by the SARS-CoV-2 S1-NTD. Moreover, concerning the origin of these NTD insertions, our findings point towards an evolutionary acquisition rather than the hypothesis of an engineered virus.", "qid": 36, "docid": "39giu15x", "rank": 58, "score": 10.965900421142578}, {"content": "Title: Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex Content: SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.", "qid": 36, "docid": "alrbutoy", "rank": 59, "score": 10.961000442504883}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD\u2013ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-020-03580-1) contains supplementary material, which is available to authorized users.", "qid": 36, "docid": "es8jsooj", "rank": 60, "score": 10.927499771118164}, {"content": "Title: Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in Spike Glycoprotein Content: SARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isn\u2019t detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in the spike gene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.", "qid": 36, "docid": "jj0n81s9", "rank": 61, "score": 10.917200088500977}, {"content": "Title: Structural and simulation analysis of hotspot residues interactions of SARS-CoV 2 with human ACE2 receptor Content: The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD. [Formula: see text]Communicated by Ramaswamy H. Sarma.", "qid": 36, "docid": "4x4ecdhn", "rank": 62, "score": 10.910599708557129}, {"content": "Title: Structural and simulation analysis of hotspot residues interactions of SARS-CoV 2 with human ACE2 receptor Content: The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD. [Image: see text] Communicated by Ramaswamy H. Sarma", "qid": 36, "docid": "g8zq3600", "rank": 63, "score": 10.910598754882812}, {"content": "Title: Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates the exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy. The structure and distribution of S on the virion surface, however, has not been characterised. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distributions of S trimers in situ on the virion surface. These results provide a basis for understanding the conformations of S present on the virion, and for studying their interactions with neutralizing antibodies.", "qid": 36, "docid": "g6jyqiep", "rank": 64, "score": 10.906200408935547}, {"content": "Title: Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors Content: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.", "qid": 36, "docid": "d4yidznm", "rank": 65, "score": 10.89840030670166}, {"content": "Title: Unveiling diffusion pattern and structural impact of the most invasive SARS-CoV-2 spike mutation Content: Starting in Wuhan, China, SARS-CoV-2 epidemics quickly propagated worldwide in less than three months, geographically sorting genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries and/or actual advantage in virus transmissibility could explain the high frequency reached by some genomic variants during the course of the outbreak. Using a suite of statistical, population genetics, and theoretical approaches, we show that the globally most represented spike protein variant (i.e., the G clade, A \u2192 G nucleotide change at genomic position 23,403; D \u2192 G amino acid change at spike protein position 614) i) underwent a significant demographic expansion in most countries not explained by stochastic effects or enhanced pathogenicity; ii) affects the spike S1/S2 furin-like site increasing its conformational plasticity (short range effect), and iii) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our study unambiguously links the spread of the G614 with a non-random process, and we hypothesize that this process is related to the selective advantage produced by a specific structural modification of the spike protein. We conclude that the different conformation of the S1/S2 proteolytic site is at the basis of the higher transmission rate of this invasive SARS-CoV-2 variant, and provide structural information to guide the design of selective and efficient drugs.", "qid": 36, "docid": "vtvxyp0j", "rank": 66, "score": 10.878000259399414}, {"content": "Title: Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins Content: Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the \u201cstanding\u201d state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the \u201clying\u201d state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines. Importance Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein.", "qid": 36, "docid": "a2cqw8kg", "rank": 67, "score": 10.874600410461426}, {"content": "Title: Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in Colombia Content: Introduction: SARS-CoV-2 is a new member of the genus Betacoronavirus, responsible for the COVID-19 pandemics. The virus crossed the species barrier and established in the human population due to its ability to exploit the ACE receptor for virus entry, which is present and abundant in several tissues, including the lung and respiratory tract, gastrointestinal tract and hearth. Virus interaction with the cellular receptor is mediated by the surface protein, known as Spike. Another structural protein of major importance in the Nucleocapsid, directly interacting with the viral RNA to form the ribonucleocapsid, considered a multifunctional protein, and being the target of the most molecular diagnostics assays. Objective: To describe the frequency of substitutions in spike and nucleocapsid proteins of SARS-CoV-2 circulating in Colombia and evaluate the frequency of these substitutions in SARS-CoV-2 sequences from other countries of South America. Materials and methods: Samples of 43 patients were included for viral RNA detection by real-time RT-PCR using the Charite-Berlin protocol for the amplification of the SARS-CoV-2 E and RdRp genes. Genome sequences were obtained through the Oxford Nanopore and Illumina MiSeq technologies, following the artic.network \"nCoV-2019 sequencing protocol\". Available genomes were consulted from GISAID, GenBank, and Genome sequence archive (GSA) and a total of 371 genomes sequences from South America were included. The genome sequences were aligned with the Muscle tool using the MEGA X software. Substitution matrices of the Colombian sequences respect to the reference genome (NC_045512) at the nucleotide and amino acid levels were generated for the spike and nucleocapsid gene. Results: substitution D614G in the amino acid sequence of spike protein was found in 86.7% of the Colombian sequences; substitutions G181V and D936Y in 2.3%, respectively. Five substitutions were found in the nucleocapsid protein, with substitution R203K and G204R being the most frequent (13.95 %) in Colombia. The substitutions D614G in Spike and R203K-G204R in nucleocapsid have a frequency of 83% and 28% respectively in sequences from South America. Conclusion: Non-synonymous substitutions were found in the spike and nucleocapsid proteins in Colombian genomes, the most frequent being D614G in Spike and R203K-G204R in nucleocapsid. These substitutions are frequent in the genomes reported for other South American countries. It is necessary to continue with genomic surveillance of the changes in Spike and Nucleocapsid proteins during the SARS-CoV-2 pandemic in Colombia and South America, even more considering that these proteins are the most commonly used antigen in serological tests.", "qid": 36, "docid": "zb034sbv", "rank": 68, "score": 10.854100227355957}, {"content": "Title: Molecular targets for COVID-19 drug development: Enlightening Nigerians about the pandemic and future treatment Content: There is little or no research initiated on enlightening Nigerians about the pathogenesis, targets for drug development, and drug repositioning for SARS-CoV-2 infection. COVID-19 is a viral infection causing symptoms like dry cough, sore throat, nasal congestion, tiredness, fever, loss of taste and smell etc. Th disease was first reported in Wuhan, China, in December 2019. The infection is caused by SARS-CoV-2, which is the third introduction of a highly pathogenic coronavirus into the human population. Coronaviruses are viruses with a positive RNA envelope assigned to \u03b1, \u03b2, \u03b3, and \u03b4 genera. Moreover, SARS-CoV-2 belongs to the \u03b2 genus. The four structural proteins of \u03b2 coronavirus are membrane (M), envelope (E), spike (S), and nucleocapsid (N) protein, mediation of coronavirus host infection is established by spike (S) protein. Therefore, the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic. It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor, viral RNA synthesis and replication, 3CLpro, RdRp, and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection. Furthermore, the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development. Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19, and mRNA-1273 targeting spike protein is the promising vaccine. However, as patient management and drug repositioning are taking place, it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection, to develop novel therapeutics.", "qid": 36, "docid": "ddt5qmls", "rank": 69, "score": 10.843799591064453}, {"content": "Title: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Content: A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.", "qid": 36, "docid": "m3j0kv0t", "rank": 70, "score": 10.840900421142578}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads. Whole-genome sequencing data offers a wide range of opportunities to study mutation dynamics. The advantage of an increasing amount of whole-genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity, and to investigate the implications of those mutations in protein stability and viral transmission. We have identified frequently mutated residues by aligning ~660 SARS-CoV-2 genomes and validated in 10,000 datasets available in GISAID Nextstrain. We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins. Among the 11 genes, surface glycoprotein, nucleocapsid, ORF1ab, and ORF8 showed frequent mutations, while envelop, membrane, ORF6, ORF7a and ORF7b showed conservation in terms of amino acid substitutions. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Some of the mutations across different proteins showed co-occurrences, suggesting their structural and/or functional interaction among different SARS-COV-2 proteins, and their involvement in adaptability and viral transmission. Analysis of protein structure stability of surface glycoprotein mutants indicated the viability of specific variants and are more prone to be temporally and spatially distributed across the globe. A similar empirical analysis of other proteins indicated the existence of important functional implications of several variants. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing, and containment of the disease.", "qid": 36, "docid": "q86nga34", "rank": 71, "score": 10.829400062561035}, {"content": "Title: Minimal system for assembly of SARS-CoV-2 virus like particles Content: SARS-CoV-2 virus is the causative agent of COVID-19. Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. The assembled SARS-CoV-2 VLPs display numerous S protein spikes ideal for vaccine development. The particles have a spike to spike size of 103 \u00b1 6 nm and a membrane diameter of 63 \u00b1 5 nm. We further show that SARS-CoV-2 VLPs dried in ambient conditions can retain their structural integrity upon repeated scans with Atomic Force Microscopy up to a peak force of 1 nN.", "qid": 36, "docid": "wfjdxgxh", "rank": 72, "score": 10.796500205993652}, {"content": "Title: Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop Content: The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission.", "qid": 36, "docid": "vembiw2k", "rank": 73, "score": 10.792699813842773}, {"content": "Title: Molecular architecture of the SARS-CoV-2 virus Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 9-11 \u00c5. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The in situ architecture of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. These characterizations have revealed the architecture of the SARS-CoV-2 virus to an unprecedented resolution, and shed lights on how the virus packs its ~30 Kb long single-segmented RNA in the ~80 nm diameter lumen. Overall, the results unveiled the molecular architecture and assembly of the SARS-CoV-2 in native context.", "qid": 36, "docid": "oo0pzspi", "rank": 74, "score": 10.789600372314453}, {"content": "Title: Flexibility and mobility of SARS-CoV-2-related protein structures Content: The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.", "qid": 36, "docid": "w62xaa4f", "rank": 75, "score": 10.781599998474121}, {"content": "Title: Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens Content: The 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics.", "qid": 36, "docid": "ch004jxy", "rank": 76, "score": 10.777999877929688}, {"content": "Title: A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 Content: Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, but does not bind the RBD. We defined the epitope of 4A8 as the N terminal domain (NTD) of the S protein by determining its cryo-EM structure in complex with the S protein to an overall resolution of 3.1 Angstrom and local resolution of 3.3 Angstrom for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.", "qid": 36, "docid": "nubewu46", "rank": 77, "score": 10.77239990234375}, {"content": "Title: Mapping active allosteric loci SARS-CoV Spike Proteins by means of Protein Contact Networks Content: Coronaviruses are a class of virus responsible of the recent outbreak of Human Severe Acute Respiratory Syndrome. The molecular machinery behind the viral entry and thus infectivity is based on the formation of the complex of virus spike protein with the angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein can trace the path to develop allosteric drugs to weaken the strength of the spike-ACE2 interface and, thus, reduce the viral infectivity. In this work we present results of the application of the Protein Contact Network (PCN) paradigm to the complex SARS-CoV spike - ACE2 relative to both 2003 SARS and the recent 2019 - CoV. Results point to a specific region, present in both structures, that is predicted to act as allosteric site modulating the binding of the spike protein with ACE2.", "qid": 36, "docid": "nrx9wqwg", "rank": 78, "score": 10.740900039672852}, {"content": "Title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.", "qid": 36, "docid": "mtq6yh25", "rank": 79, "score": 10.735899925231934}, {"content": "Title: Spike protein fusion loop controls SARS-CoV-2 fusogenicity and infectivity Content: The Spike is a hallmark coronavirus protein that determines virus fusion, entry and spread in the host, and thus holds clues for the rapid spread of the SARS-CoV-2 pandemic. We have investigated the Spike from six \u03b2-coronaviruses, including the SARS-CoV-2, and find that their surface-exposed fusion peptides constituting the fusion loop are spatially organized contiguous to each other to work synergistically for triggering the virus-host membrane fusion process. The SARS-CoV-2 fusion peptides have unique physicochemical properties, accrued in part from the presence of consecutive prolines that impart backbone rigidity which aids the virus fusogenicity. The specific contribution of these prolines has been inferred from comparative studies of their deletion mutant in a fellow murine \u03b2-coronavirus MHV-A59 that show significantly diminished fusogenicity in vitro and associated pathogenesis in vivo. The Spike cleavage-linked priming and fusogenic conformational transition steered by the fusion loop may be critical for the SARS-CoV-2 spread. Summary The Spike protein on the SARS-CoV-2 surface is the prime mediator of COVID-191 because of its central role in virus-host attachment, virus-entry, and virus-spread2. The contagious nature of SARS-CoV-2 infection has been attributed to dense glycosylation of the Spike glycoprotein3, its high affinity of binding to human ACE2 receptor4, and cleavage5. While these may be imperative, it does not explain the uncontrolled infectivity. Here we show that properties of the fusion peptides constituting the fusion loop of SARS-CoV-2 Spike that triggers the virus fusion, distinguishes it from the other five \u03b2-coronaviruses. The SARS-CoV-2 Spike trimer surface is relatively more hydrophobic, including the surface contributed by the fusion peptides. The fusion peptides are structurally rigid owing to its consecutive prolines, aromatic/hydrophobic clusters, a stretch of consecutive \u03b2-branched amino acids, and the hydrogen bonds. The role of rigidity accrued from the presence of consecutive prolines contributing to virus fusogenicity can be deciphered from our previous murine \u03b2-coronavirus, MHV-A59 studies6. The synergy brought about by the global location of the surface exposed fusion peptides, their physicochemical features, and the fusogenic conformational transition appears to drive the fusion process, which may explain the severity of the infection and widespread nature of the COVID-19 pandemic.", "qid": 36, "docid": "7xd0msyk", "rank": 80, "score": 10.733499526977539}, {"content": "Title: Comparing the binding interactions in the receptor binding domains of SARS-CoV-2 and SARS-CoV Content: COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins of SARS-CoV and SARS-CoV-2 to the ACE2. We found that the SARS-CoV-2 binds to ACE2 stronger than SARS-CoV by 7 kcal/mol, due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies are resulting from the salt-bridges formed between R426 and ACE2-E329 in case of SARS-CoV and K417 and ACE2-D30 for SARS-CoV2. In addition, there is no significant contribution from a single mutant to the binding energies. However, these mutations induce sophisticated structural changes that enhance the binding energies. Our results also indicate that the SARS-CoV-2 is unlikely a lab engineered virus.", "qid": 36, "docid": "xpbcoipf", "rank": 81, "score": 10.729599952697754}, {"content": "Title: Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition Content: Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycoform) the level of surface shielding is disproportionately high at 42%.", "qid": 36, "docid": "rwlpkf7n", "rank": 82, "score": 10.729399681091309}, {"content": "Title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV Content: The outbreak of COVID-19, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein are in the \u201cup\u201d conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain.", "qid": 36, "docid": "f03ka7bd", "rank": 83, "score": 10.699299812316895}, {"content": "Title: Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism Content: The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.", "qid": 36, "docid": "vy1obqyp", "rank": 84, "score": 10.687600135803223}, {"content": "Title: Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism Content: The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.", "qid": 36, "docid": "wynyrumi", "rank": 85, "score": 10.687599182128906}, {"content": "Title: Potential involvement of monoamine oxidase activity in SARS-COV2 infection and delirium onset Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of extra-respiratory signs and symptoms. One such manifestation is delirium, an acute confusional state occurring in 60-70% of severe SARS-CoV-2 cases. Delirium is also a common clinical syndrome following planned orthopedic surgery. This investigation initially explored the underlying role of metabolism in delirium-susceptibility in this setting. Metabolomics profiles of cerebrospinal fluid (CSF) and blood taken prior to surgery found significant concentration differences of several amino acids, acylcarnitines and polyamines were observed in delirium-prone patients. Phenethylamine (PEA) concentrations in delirium-prone patients was significantly lower in CSF than in blood, whilst in age- and gender-matched controls the opposite was observed (adjusted p values: 1.8x10-6 (control) and 1.788x10-10 (delirium)). PEA is metabolised by monoamine oxidase B (MAOB), a putative enzyme target for the treatment of Alzheimers disease, Parkinsons disease and depression. Our computational structural comparisons of MAOB and angiotensin converting enzyme (ACE) 2 found high similarity, specifically within the SARS-CoV-2 spike protein. MAOB structural alignment to ACE2 was 51% overall, but this was over 95% in the ACE2-spike protein binding region. Thus, it is possible that the spike protein interacts with MAOB on a molecular level. A previously published metabolomic dataset of control subjects and patients with either mild or severe COVID-19 was then analysed. Major concentration differences in some metabolites attributed to altered MAO activity were detected. Therefore, our hypothesis is that the SARS-CoV-2 influences MAOB activity, which is one potential cause for the many observed neurological and platelet based complications of SARS-CoV-2 infection.", "qid": 36, "docid": "xf0kkrv0", "rank": 86, "score": 10.666600227355957}, {"content": "Title: Static All-Atom Energetic Mappings of the SARS-Cov-2 Spike Protein with Potential Latch Identification of the Down State Protomer Content: The SARS-Cov-2 virion responsible for the current world-wide pandemic Covid-19 has a characteristic Spike protein (S) on its surface that embellishes both a prefusion state and fusion state. The prefusion Spike protein (S) is a large trimeric protein where each protomer may be in a so-called Up state or Down state, depending on the configuration of its receptor binding domain (RBD). The Up state is believed to allow binding of the virion to ACE-2 receptors on human epithelial cells, whereas the Down state is believed to be relatively inactive or reduced in its binding behavior. We have performed detailed all-atom, dominant energy landscape mappings for noncovalent interactions (charge, partial charge, and van der Waals) of the SARS-Cov-2 Spike protein in its static prefusion state based on recent structural information. We included both interchain interactions and intrachain (domain) interactions in our mappings in order to determine any telling differences (different so-called \u201cglue\u201d points or \u201chot spots\u201d) between residues in the Up and Down state protomers. In general, the S2 or fusion machinery domain of S is relatively rigid with strong noncovalent interactions facilitated by helical secondary structures, whereas the S1 domain, which contains the RBD and N-terminal domain (NTD), is relatively more flexible and characterized by beta strand structural motifs. The S2 domain demonstrated no appreciable energetic differences between Up and Down protomers, including interchain as well as each protomer\u2019s intrachain, S1\u2013S2 interactions. However, the S1 domain interactions across neighboring protomers, which include the RBD-NTD cross chain interactions, showed energetic differences between Up-Down and Down-Down neighboring protomers. Surprisingly, the Up-Down, RBD-NTD interactions were overall stronger and more numerous than the Down-Down cross chain interactions, including the appearance of the three residue sequence ALA520-PRO521-ALA522 associated with a turn structure in the RBD of the Up state. Additionally, our intrachain dominant energy mappings within each protomer, identified a significant \u201cglue\u201d point or possible latch for the Down state protomer between the S1 subdomain, SD1 and the RBD domain of the same protomer that was completely missing in the Up state protomer analysis. Ironically, this dominant energetic interaction in the Down state protomer involved the backbone atoms of the same three residue sequence ALA520-PRO521-ALA522 of the RBD with the R-group of GLN564 in the SD1 domain. Thus, this same three residue sequence acts as a stabilizer of the RBD in the Up conformation through its interactions with its neighboring NTD chain and a kind of latch in the Down state conformation through its interactions with its own SD1 domain. The dominant interaction energy residues identified here are also conserved across reported variations of SARS-Cov-2, as well as the closely related virions SARS-Cov and the bat corona virus RatG13. However, these results are all based on static structure analysis and large scale dynamic simulations will be necessary to further investigate these findings. Nonetheless, static dominant energy landscape mappings represents a starting point for more detailed dynamic analyses and hopefully an improved understanding at the structure-function relationship of this highly complex protein.", "qid": 36, "docid": "z2e7shee", "rank": 87, "score": 10.660799980163574}, {"content": "Title: SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes Content: Background The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality in COVID-19 patients. It is unclear whether cardiac injury may have been caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here we investigate whether human cardiomyocytes are permissive for SARS-CoV-2 infection. Methods Infection was induced by two strains of SARS-CoV-2 (FFM1 and FFM2) in human induced pluripotent stem cells-derived cardiomyocytes (hiPS-CM) and in two models of human cardiac tissue. Results We show that SARS-CoV-2 infects hiPS-CM as demonstrated by detection of intracellular double strand viral RNA and viral spike glycoprotein protein expression. Increasing concentrations of virus RNA are detected in supernatants of infected cardiomyocytes, which induced infections in CaCo-2 cell lines documenting productive infections. SARS-COV-2 infection induced cytotoxic and pro-apoptotic effects and abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signaling, apoptosis and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a iPS-derived human 3D cardiosphere tissue models. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Conclusions The demonstration that cardiomyocytes are permissive for SARS-CoV-2 infection in vitro warrants the further in depth monitoring of cardiotoxic effects in COVID-19 patients. Clinical Perspective What is New? This study demonstrates that human cardiac myocytes are permissive for SARS-CoV-2 infection. The study documents that SARS-CoV-2 undergoes a full replicatory circle and induces a cytotoxic response in cardiomyocytes. Infection was confirmed in two cardiac tissue models, including living human heart slices. What are the Clinical Implications? The study may provide a rational to explain part of the cardiotoxicity observed in COVID-19 patients The demonstration of direct cardiotoxicity induced by SARS-CoV-2 warrants an in depth further analysis of cardiac tissue of COVID-19 patients and a close monitoring for putative direct cardiomyocyte injury. The established models can be used to test novel therapeutic approaches targeting COVID-19.", "qid": 36, "docid": "46evycyn", "rank": 88, "score": 10.660099983215332}, {"content": "Title: How the COVID-19 Overcomes the Battle? An Approach to Virus Structure. Content: Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.", "qid": 36, "docid": "5onj6s3n", "rank": 89, "score": 10.639800071716309}, {"content": "Title: How the COVID-19 Overcomes the Battle? An Approach to Virus Structure Content: Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.", "qid": 36, "docid": "5wakh15h", "rank": 90, "score": 10.639799118041992}, {"content": "Title: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD Content: Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 7 million confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved cryo-EM structure of ACE2 in complex with SARS-CoV-2-RBD, we observed that the ACE2 peptidase domain (PD) \u03b11 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD \u03b11 helix (SBP1) composed entirely of proteinogenic amino acids. Chemical synthesis of SBP1 was complete in 1.5 hours, and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry (BLI) revealed that SBP1 associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein obtained from Sino Biological. Association of SBP1 was not observed to an appreciable extent to HEK cell-expressed SARS-CoV-2-RBD proteins and insect-derived variants acquired from other vendors. Moreover, competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD. Further investigations are ongoing to gain insight into the molecular and structural determinants of the variable binding behavior to different SARS-CoV-2-RBD protein variants.", "qid": 36, "docid": "yi6yu5l1", "rank": 91, "score": 10.628499984741211}, {"content": "Title: Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site Content: An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an \u201cup\u201d and \u201cdown\u201d state. In addition, the trimer cavity may function as a \u201cbouncing spring\u201d that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses.", "qid": 36, "docid": "db2rqz4d", "rank": 92, "score": 10.628399848937988}, {"content": "Title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity Content: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "qid": 36, "docid": "t8q99tlq", "rank": 93, "score": 10.619799613952637}, {"content": "Title: Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion Content: The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.", "qid": 36, "docid": "mcsdem7y", "rank": 94, "score": 10.607000350952148}, {"content": "Title: Properties of Coronavirus and SARS-CoV-2. Content: were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (\u03b1,\u03b2,\u03b3,\u03b4), human coronaviruses (HCoVs) are classified under \u03b1-CoV (HCoV-229E and NL63) and \u03b2-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a \u03b2-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.", "qid": 36, "docid": "713ey27b", "rank": 95, "score": 10.585800170898438}, {"content": "Title: Properties of Coronavirus and SARS-CoV-2 Content: were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (&#945;,\u00df,\u00ce\u00b3,\u00ce\u00b4), human coronaviruses (HCoVs) are classified under &#945;-CoV (HCoV-229E and NL63) and \u00df-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a \u00df-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.", "qid": 36, "docid": "bm0ldeue", "rank": 96, "score": 10.585799217224121}, {"content": "Title: Structural and Functional Implications of Spike Protein Mutational Landscape in SARS-CoV-2 Content: SARS-CoV-2, the causative agent of COVID-19 pandemic, is an RNA virus prone to mutations. Interaction of SARS-CoV-2 Spike (S) protein with the host cell receptor, Angiotensin-I Converting Enzyme 2 (ACE2) is pivotal for attachment and entry of the virus. Yet, natural mutations acquired on S protein during the pandemic and their impact on viral infectivity, transmission dynamics and disease pathogenesis remains poorly understood. Here, we analysed 2952 SARS-CoV-2 genomes across the globe, and identified a total of 1815 non-synonymous mutations in the S-protein that fall into 54 different types. We observed that six of these distinct mutations were located in the Receptor Binding Domain (RBD) region that directly engages host ACE2. Molecular phylogenetic analysis revealed that these RBD mutations cluster into distinct phyletic clades among global subtypes of SARS-CoV-2 implying possible emergence of novel sublineages of the strain. Structure-guided homology modelling and docking analysis predicted key molecular rearrangements in the ACE2 binding interface of RBD mutants that could result in altered virus-host interactions. We propose that our findings could be significant in understanding disease dynamics and in developing vaccines, antibodies and therapeutics for COVID-19. Importance COVID-19 pandemic shows considerable variations in disease transmission and pathogenesis globally, yet reasons remain unknown. Our study identifies key S-protein mutations prevailing in SARS-CoV-2 strain that could alter viral attachment and infectivity. We propose that the interplay of these mutations could be one of the factors driving global variations in COVID-19 spread. In addition, the mutations identified in this study could be an important indicator in predicting efficacies of vaccines, antibodies and therapeutics that target SARS-CoV-2 RBD-ACE2 interface.", "qid": 36, "docid": "40xsypzt", "rank": 97, "score": 10.57960033416748}, {"content": "Title: Distinct conformational states of SARS-CoV-2 spike protein Content: The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes - the first key step of viral infection. Here we report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1\u00c5 resolution) and postfusion (3.3\u00c5 resolution) conformations, respectively. The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance our understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.", "qid": 36, "docid": "muwwyktk", "rank": 98, "score": 10.560099601745605}, {"content": "Title: SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain Content: Virus genome sequence variants that appear over the course of an outbreak can be exploited to map the trajectory of the virus from one susceptible host to another. While such variants are usually of no functional significance, in some cases they may allow the virus to transmit faster, change disease severity, or confer resistance to antiviral therapies. Since the discovery of SARS-CoV-2 as the cause of COVID-19, the virus has spread around the globe, and thousands of SARS-CoV-2 genomes have been sequenced. The rate of sequence variation among SARS-CoV-2 isolates is modest for an RNA virus but the enormous number of human-to-human transmission events has provided abundant opportunity for selection of sequence variants. Among these, the SARS-CoV-2 Spike protein variant, D614G, was not present in the presumptive common ancestor of this zoonotic virus but was first detected in late January in Germany and China. The D614G variant steadily increased in frequency and now constitutes >97% of isolates world-wide, raising the question whether D614G confers a replication advantage to SARS-CoV-2. Structural models predict that D614G would disrupt contacts between the S1 and S2 domains of the Spike protein and cause significant shifts in conformation. Using single-cycle vectors we showed that D614G is three to nine-fold more infectious than the ancestral form on human lung and colon cell lines, as well as on other human cell lines rendered permissive by ectopic expression of human ACE2 and TMPRSS2, or by ACE2 orthologues from pangolin, pig, dog, or cat. Nonetheless, monoclonal antibodies targeting the receptor binding domain of the SARS-CoV-2 Spike protein retain full neutralization potency. These results suggest that D614G was selected for increased human-to-human transmission, that it contributed to the rapidity of SARS-CoV-2 spread around the world, and that it does not confer resistance to antiviral therapies targeting the receptor binding domain.", "qid": 36, "docid": "e6jt8yhs", "rank": 99, "score": 10.557900428771973}, {"content": "Title: Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020 Content: Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.", "qid": 36, "docid": "uhru7rn8", "rank": 100, "score": 10.552900314331055}]}
{"query": "What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence?", "hits": [{"content": "Title: Children\u2019s Hospital Los Angeles COVID-19 Analysis Research Database (CARD) - A Resource for Rapid SARS-CoV-2 Genome Identification Using Interactive Online Phylogenetic Tools Content: Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and monitoring the continuous evolution of the SARS-CoV-2 viral genomes. The Children\u2019s Hospital, Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) (https://covid19.cpmbiodev.net/) is a comprehensive genomic resource that provides access to full-length SARS-CoV-2 viral genomes and associated meta-data for over 30,000 (as of May 20, 2020) isolates collected from global sequencing repositories and the sequencing performed at the Center for Personalized Medicine (CPM) at CHLA. Reference phylogenetic trees of global and USA viral isolates were constructed and are periodically updated using selected high quality SARS-CoV-2 genome sequences. These provide the baseline and analytical context for identifying the origin of a viral infection, as well as the relatedness of SARS-CoV-2 genomes of interest. A web-based and interactive Phylogenetic Tree Browser supports flexible tree manipulation and advanced analysis based on keyword search while highlighting time series animation, as well as subtree export for graphical representation or offline exploration. A Virus Genome Tracker accepts complete or partial SARS-CoV-2 genome sequence, compares it against all available sequences in the database (>30,000 at time of writing), detects and annotates the variants, and places the new viral isolate within the global or USA phylogenetic contexts based upon variant profiles and haplotype comparisons, in a few seconds. The generated analysis can potentially aid in genomic surveillance to trace the transmission of any new infection. Using CHLA CARD, we demonstrate the identification of a candidate outbreak point where 13 of 31 CHLA internal isolates may have originated. We also discovered multiple indels of unknown clinical significance in the orf3a gene, and revealed a number of USA-specific variants and haplotypes.", "qid": 37, "docid": "2kbi9drl", "rank": 1, "score": 14.361200332641602}, {"content": "Title: A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis Content: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non-peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood-based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "qid": 37, "docid": "dqyjdast", "rank": 2, "score": 14.325599670410156}, {"content": "Title: A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis Content: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non\u2013peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood\u2013based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "qid": 37, "docid": "hze05jnf", "rank": 3, "score": 14.32559871673584}, {"content": "Title: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome Content: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "qid": 37, "docid": "shn7vx3d", "rank": 4, "score": 14.167499542236328}, {"content": "Title: Large-Scale Phylogenetic Analysis of Emerging Infectious Diseases Content: Microorganisms that cause infectious diseases present critical issues of national security, public health, and economic welfare. For example, in recent years, highly pathogenic strains of avian influenza have emerged in Asia, spread through Eastern Europe, and threaten to become pandemic. As demonstrated by the coordinated response to Severe Acute Respiratory Syndrome (SARS) and influenza, agents of infectious disease are being addressed via large-scale genomic sequencing. The goal of genomic sequencing projects are to rapidly put large amounts of data in the public domain to accelerate research on disease surveillance, treatment, and prevention. However, our ability to derive information from large comparative genomic datasets lags far behind acquisition. Here we review the computational challenges of comparative genomic analyses, specifically sequence alignment and reconstruction of phylogenetic trees. We present novel analytical results on two important infectious diseases, Severe Acute Respiratory Syndrome (SARS) and influenza. SARS and influenza have similarities and important differences both as biological and comparative genomic analysis problems. Influenza viruses (Orthymxyoviridae) are RNA based. Current evidence indicates that influenza viruses originate in aquatic birds from wild populations. Influenza has been studied for decades via well-coordinated international efforts. These efforts center on surveillance via antibody characterization of the hemagglutinin (HA) and neuraminidase (N) proteins of the circulating strains to inform vaccine design. However, we still do not have a clear understanding of (1) various transmission pathways such as the role of intermediate hosts like swine and domestic birds and (2) the key mutation and genomic recombination events that underlie periodic pandemics of influenza. In the past 30 years, sequence data from HA and N loci has become an important data type. In the past year, full genomic data has become prominent. These data present exciting opportunities to address unanswered questions in influenza pandemics. SARS is caused by a previously unrecognized lineage of coronavirus, SARS-CoV, which like influenza has an RNA based genome. Although SARS-CoV is widely believed to have originated in animals, there remains disagreement over the candidate animal source that lead to the original outbreak of SARS. In contrast to the long history of the study of influenza, SARS was only recognized in late 2002 and the virus that causes SARS has been documented primarily by genomic sequencing. In the past, most studies of influenza were performed on a limited number of isolates and genes suited to a particular problem. Major goals in science today are to understand emerging diseases in broad geographic, environmental, societal, biological, and genomic contexts. Synthesizing diverse information brought together by various researchers is important to find out what can be done to prevent future outbreaks [JON03]. Thus comprehensive means to organize and analyze large amounts of diverse information are critical. For example, the relationships of isolates and patterns of genomic change observed in large datasets might not be consistent with hypotheses formed on partial data. Moreover when researchers rely on partial datasets, they restrict the range of possible discoveries. Phylogenetics is well suited to the complex task of understanding emerging infectious disease. Phylogenetic analyses can test many hypotheses by comparing diverse isolates collected from various hosts, environments, and points in time and organizing these data into various evolutionary scenarios. The products of a phylogenetic analysis are a graphical tree of ancestor\u2013descendent relationships and an inferred summary of mutations, recombination events, host shifts, geographic, and temporal spread of the viruses. However, this synthesis comes at a price. The cost of computation of phylogenetic analysis expands combinatorially as the number of isolates considered increases. Thus, large datasets like those currently produced are commonly considered intractable. We address this problem with synergistic development of heuristics tree search strategies and parallel computing.", "qid": 37, "docid": "cndb031c", "rank": 5, "score": 14.102800369262695}, {"content": "Title: [Analysis on the SARS-CoV genome of PUMC01 isolate]. Content: OBJECTIVE To perform variation and phylogenetics analysis on the SARS-CoV genome sequence (PUMC01) isolated in the Peking Union Medical College Hospital. METHODS The cDNA library of SARS-CoV (PUMC01 isolate) was constructed by means of random-priming strategy. Random selected plasmid was sequenced and the genome sequence of SARS-CoV-PUMC01 was assembled by conventional methods (The Genebank Accession No. of SARS-CoV-PUMC01 is AY350750). The variation and phylogenetics analysis were performed by comparing the PUMC01 sequence with other SARS-CoV isolates. RESULTS Ten variation sites were found by comparing PUMC01 isolate with Tor2 and Urbani isolates. In phylogenetic analysis of 18 SARS-CoV isolates, two classes were observed and there is different differential time between these two classes and the different isolates in each class. CONCLUSIONS The evidence of phylogenetic analysis of different SARS-CoV isolates from different region is instructive for understanding the clinical relations between the different isolates and the transmission chain of SARS-CoV.", "qid": 37, "docid": "agox0lbq", "rank": 6, "score": 14.04319953918457}, {"content": "Title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission Content: Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.", "qid": 37, "docid": "8klkojpo", "rank": 7, "score": 13.96030044555664}, {"content": "Title: A distinct phylogenetic cluster of Indian SARS-CoV-2 isolates Content: From an isolated epidemic, COVID-19 has now emerged as a global pandemic. The availability of genomes in the public domain following the epidemic provides a unique opportunity to understand the evolution and spread of the SARS-CoV-2 virus across the globe. The availability of whole genomes from multiple states in India prompted us to analyse the phylogenetic clusters of genomes in India. We performed whole-genome sequencing for 64 genomes making a total of 361 genomes from India, followed by phylogenetic clustering, substitution analysis, and dating of the different phylogenetic clusters of viral genomes. We describe a distinct phylogenetic cluster (Clade I / A3i) of SARS-CoV-2 genomes from India, which encompasses 41% of all genomes sequenced and deposited in the public domain from multiple states in India. Globally 3.5% of genomes, which till date could not be mapped to any distinct known cluster fall in this newly defined clade. The cluster is characterized by a core set of shared genetic variants \u2013 C6312A (T2016K), C13730T (A88V/A97V), C23929T, and C28311T (P13L). Further, the cluster is also characterized by a nucleotide substitution rate of 1.4 \u00d7 10\u22123 variants per site per year, lower than the prevalent A2a cluster, and predominantly driven by variants in the E and N genes and relative sparing of the S gene. Epidemiological assessments suggest that the common ancestor emerged in the month of February 2020 and possibly resulted in an outbreak followed by countrywide spread, as evidenced by the low divergence of the genomes from across the country. To the best of our knowledge, this is the first comprehensive study characterizing the distinct and predominant cluster of SARS-CoV-2 in India.", "qid": 37, "docid": "x6hln4wk", "rank": 8, "score": 13.828800201416016}, {"content": "Title: Full-genome sequences of the first two SARS-CoV-2 viruses from India Content: Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "qid": 37, "docid": "35wfw3zn", "rank": 9, "score": 13.797599792480469}, {"content": "Title: Full-genome sequences of the first two SARS-CoV-2 viruses from India Content: BACKGROUND & OBJECTIVES: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. METHODS: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. RESULTS: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. INTERPRETATION & CONCLUSIONS: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "qid": 37, "docid": "vhb280gz", "rank": 10, "score": 13.797598838806152}, {"content": "Title: Phylodynamics of SARS-CoV-2 transmission in Spain Content: Objectives SARS-CoV-2 whole-genome analysis has identified three large clades spreading worldwide, designated G, V and S. This study aims to analyze the diffusion of SARS-CoV-2 in Spain/Europe. Methods Maximum likelihood phylogenetic and Bayesian phylodynamic analyses have been performed to estimate the most probable temporal and geographic origin of different phylogenetic clusters and the diffusion pathways of SARS-CoV-2. Results Phylogenetic analyses of the first 28 SARS-CoV-2 whole genome sequences obtained from patients in Spain revealed that most of them are distributed in G and S clades (13 sequences in each) with the remaining two sequences branching in the V clade. Eleven of the Spanish viruses of the S clade and six of the G clade grouped in two different monophyletic clusters (S-Spain and G-Spain, respectively), with the S-Spain cluster also comprising 8 sequences from 6 other countries from Europe and the Americas. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in the city of Wuhan, China, around November 24, 2019, with a 95% highest posterior density (HPD) interval from October 30-December 17, 2019. The origin of S-Spain and G-Spain clusters were estimated in Spain around February 14 and 18, 2020, respectively, with a possible ancestry of S-Spain in Shanghai. Conclusions Multiple SARS-CoV-2 introductions have been detected in Spain and at least two resulted in the emergence of locally transmitted clusters, with further dissemination of one of them to at least 6 other countries. These results highlight the extraordinary potential of SARS-CoV-2 for rapid and widespread geographic dissemination.", "qid": 37, "docid": "wg86ws3b", "rank": 11, "score": 13.670900344848633}, {"content": "Title: SARS-CoV Infection Was from at Least Two Origins in the Taiwan Area Content: OBJECTIVE: Severe acute respiratory syndrome (SARS) is caused by a new coronavirus. Genomic sequence analysis will provide the molecular epidemiology and help to develop vaccines. METHODS: We developed a rapid method to amplify and sequence the whole SARS-CoV genome from clinical specimens. The technique employed one-step multiplex RT-PCR to amplify the whole SARS-CoV genome, and then nested PCR was performed to amplify a 2-kb region separately. The PCR products were sequenced. RESULTS: We sequenced the genomes of SARS-CoV from 3 clinical specimens obtained in Taiwan. The sequences were similar to those reported by other groups, except that 17 single nucleotide variations and two 2-nucleotide deletions, and a 1-nucleotide deletion were found. All the variations in the clinical specimens did not alter the amino acid sequence. Of these 17 sequenced variants, two loci (positions 26203 and 27812) were segregated together as a specific genotype-T:T or C:C. Phylogenetic analysis showed two major clusters of SARS patients in Taiwan. CONCLUSION: We developed a very economical and rapid method to sequence the whole genome of SARS-CoV, which can avoid cultural influence. From our results, SARS patients in Taiwan may be infected from two different origins.", "qid": 37, "docid": "79uxm3bg", "rank": 12, "score": 13.610300064086914}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario Content: Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 37, "docid": "2nvk7glh", "rank": 13, "score": 13.490500450134277}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario. Content: Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 37, "docid": "bcx51aci", "rank": 14, "score": 13.490499496459961}, {"content": "Title: Phylogenetic analysis of SARS-CoV-2 genomes in Turkey Content: COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first 30 SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find 2 of the seventeen subclusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.", "qid": 37, "docid": "m3505b5w", "rank": 15, "score": 13.482199668884277}, {"content": "Title: Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey Content: COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first thirty SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find two of the seventeen sub-clusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.", "qid": 37, "docid": "7u97in7o", "rank": 16, "score": 13.435700416564941}, {"content": "Title: Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition Content: Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain \"MESEFR\" and \"SYLTPG\" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions \"VGGNY\" and \"EIYQAGSTPCNGV\" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.", "qid": 37, "docid": "n9rwixr4", "rank": 17, "score": 13.396200180053711}, {"content": "Title: Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus Content: Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11, 132 SARS-CoV-2 patients in the GISAID (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7, 640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index (Jaccard, 1901; Tan et al., 2005; Prokopenko et al., 2016; Schlauch et al., 2017). Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.", "qid": 37, "docid": "xnamt7q4", "rank": 18, "score": 13.336199760437012}, {"content": "Title: Insights into molecular evolution recombination of pandemic SARS-CoV-2 using Saudi Arabian sequences Content: The recently emerged SARS-CoV-2 (Coronaviridae; Betacoronavirus) is the underlying cause of COVID-19 disease. Here we assessed SARS-CoV2 from the Kingdom of Saudi Arabia alongside sequences of SARS-CoV, bat SARS-like CoVs and MERS-CoV, the latter currently detected in this region. Phylogenetic analysis, natural selection investigation and genome recombination analysis were performed. Our analysis showed that all Saudi SARS-CoV-2 sequences are of the same origin and closer proximity to bat SARS-like CoVs, followed by SARS-CoVs, however quite distant to MERS-CoV. Moreover, genome recombination analysis revealed two recombination events between SARS-CoV-2 and bat SARS-like CoVs. This was further assessed by S gene recombination analysis. These recombination events may be relevant to the emergence of this novel virus. Moreover, positive selection pressure was detected between SARS-CoV-2, bat SL-CoV isolates and human SARS-CoV isolates. However, the highest positive selection occurred between SARS-CoV-2 isolates and 2 bat-SL-CoV isolates (Bat-SL-RsSHC014 and Bat-SL-CoVZC45). This further indicates that SARS-CoV-2 isolates were adaptively evolved from bat SARS-like isolates, and that a virus with originating from bats triggered this pandemic. This study thuds sheds further light on the origin of this virus. AUTHOR SUMMARY The emergence and subsequent pandemic of SARS-CoV-2 is a unique challenge to countries all over the world, including Saudi Arabia where cases of the related MERS are still being reported. Saudi SARS-CoV-2 sequences were found to be likely of the same or similar origin. In our analysis, SARS-CoV-2 were more closely related to bat SARS-like CoVs rather than to MERS-CoV (which originated in Saudi Arabia) or SARS-CoV, confirming other phylogenetic efforts on this pathogen. Recombination and positive selection analysis further suggest that bat coronaviruses may be at the origin of SARS-CoV-2 sequences. The data shown here give hints on the origin of this virus and may inform efforts on transmissibility, host adaptation and other biological aspects of this virus.", "qid": 37, "docid": "wim5q9a5", "rank": 19, "score": 13.318699836730957}, {"content": "Title: Evolutionary relationships and sequence\u2010structure determinants in human SARS coronavirus\u20102 spike proteins for host receptor recognition Content: Coronavirus disease 2019 (COVID\u201019) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus\u20102 (SARS CoV\u20102). The SARS CoV\u20102 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV\u20102 via their glycosylated spike proteins recognize the human angiotensin converting enzyme\u20102 (ACE\u20102) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV\u20102 from various host sources in order to analyze the specificity in SARS CoV\u20102 spike proteins required for causing infection in humans. Our results show that among the genomes analysed, two sequence regions in the N\u2010terminal domain (NTD); \"MESEFR\" and \"SYLTPG\" are specific to human SARS CoV\u20102. In the receptor binding domain (RBD), two sequence regions; \"VGGNY\" and \"EIYQAGSTPCNGV\" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE\u20102 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources and human SARS CoV\u20102 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV\u20102 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV\u20102. This article is protected by copyright. All rights reserved.", "qid": 37, "docid": "1dxu14b1", "rank": 20, "score": 13.259099960327148}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient\u2019s sequence clustered with sequences from Germany while the tourist\u2019s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients\u2019 sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 37, "docid": "48ul34xo", "rank": 21, "score": 13.250399589538574}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient's sequence clustered with sequences from Germany while the tourist's sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients' sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 37, "docid": "o6rr66kc", "rank": 22, "score": 13.250398635864258}, {"content": "Title: Genomic surveillance and phylogenetic analysis reveal multiple introductions of SARS-CoV-2 into a global travel hub in the Middle East Content: International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analyzed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2.", "qid": 37, "docid": "pov7oi1l", "rank": 23, "score": 13.225799560546875}, {"content": "Title: Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets Content: To identify features in the genome of the SARS-CoV-2 pathogen responsible for the COVID-19 pandemic that may contribute to its viral replication, host pathogenicity, and vulnerabilities, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes. Our analyses suggest the presence of unique sequence signatures in the 3\u2019-untranslated region (UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2, SARS-CoV, as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host microRNA-mediated interaction between the 3\u2019-UTR and human microRNA hsa-miR-1307-3p based on predicted, yet extensive, complementary base-pairings and similar interactions involving the Influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3\u2019-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection, and the exploitation of conserved features in the 3\u2019-UTR as therapeutic targets warrant further investigation.", "qid": 37, "docid": "gu3a677i", "rank": 24, "score": 13.218299865722656}, {"content": "Title: Phyloevolutionary analysis of SARS-CoV-2 in Nigeria Content: Abstract Background Phyloepidemiologic approaches have given specific insight to understanding emergence and evolution of infection. Knowledge on the outbreak and spread of SARS-CoV-2 in Nigeria would assist in providing preventive measures to reduce transmission among populations at risk. Therefore, this study aimed at investigating the evolution of SARS-CoV-2 in Nigeria. Materials and Method A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFluTM database on March 29th 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the patient and the collection date. Other sequences were not selected because they were short, contained artefacts, not from original source or had insufficient information. Evolutionary history was inferred using Maximum Likelihood method based on the General Time Reversible model. Phylogenetic tree was constructed to determine the common ancestor of each strain. Results The phylogenetic analysis showed the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27,972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. Conclusion The study evidently showed the entire outbreak of COVID-19 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.", "qid": 37, "docid": "aejbfk3l", "rank": 25, "score": 13.121800422668457}, {"content": "Title: The UCSC SARS-CoV-2 Genome Browser Content: Background Researchers are generating molecular data pertaining to the SARS-CoV-2 RNA genome and its proteins at an unprecedented rate during the COVID-19 pandemic. As a result, there is a critical need for rapid and continuously updated access to the latest molecular data in a format in which all data can be quickly cross-referenced and compared. We adapted our genome browser visualization tool to the viral genome for this purpose. Molecular data, curated from published studies or from database submissions, are mapped to the viral genome and grouped together into \u201cannotation tracks\u201d where they can be visualized along the linear map of the viral genome sequence and programmatically downloaded in standard format for analysis. Results The UCSC Genome Browser for SARS-CoV-2 (https://genome.ucsc.edu/covid19.html) provides continuously updated access to the mutations in the many thousands of SARS-CoV-2 genomes deposited in GISAID and the international nucleotide sequencing databases, displayed alongside phylogenetic trees. These data are augmented with alignments of bat, pangolin, and other animal and human coronavirus genomes, including per-base evolutionary rate analysis. All available annotations are cross-referenced on the virus genome, including those from major databases (PDB, RFAM, IEDB, UniProt) as well as up-to-date individual results from preprints. Annotated data include predicted and validated immune epitopes, promising antibodies, RT-PCR and sequencing primers, CRISPR guides (from research, diagnostics, vaccines, and therapies), and points of interaction between human and viral genes. As a community resource, any user can add manual annotations which are quality checked and shared publicly on the browser the next day. Conclusions We invite all investigators to contribute additional data and annotations to this resource to accelerate research and development activities globally. Contact us at genome-www@soe.ucsc.edu with data suggestions or requests for support for adding data. Rapid sharing of data will accelerate SARS-CoV-2 research, especially when researchers take time to integrate their data with those from other labs on a widely-used community browser platform with standardized machine-readable data formats, such as the SARS-CoV-2 Genome Browser.", "qid": 37, "docid": "gmk4qo4i", "rank": 26, "score": 13.023799896240234}, {"content": "Title: Analyzing hCov genome sequences: Applying Machine Intelligence and beyond Content: Covid-19 pandemic, caused by the sars-cov-2 strain of coronavirus, has affected millions of people all over the world and taken thousands of lives. It is of utmost importance that the character of this deadly virus be studied and its nature be analysed. We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. In a nutshell, we have prepared an analysis pipeline for hCov genome sequences leveraging the power of machine intelligence and uncovered what remained apparently shrouded by raw data.", "qid": 37, "docid": "0x90yubt", "rank": 27, "score": 12.98270034790039}, {"content": "Title: Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states Content: The first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity (\u03c0) values revealed the presence of higher proportions of low frequency variants and negative Tajima\u2019s D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.", "qid": 37, "docid": "9slpoyz7", "rank": 28, "score": 12.94540023803711}, {"content": "Title: Early Phylogenetic Diversification of SARS-CoV-2: Determination of Variants and the Effect on Epidemiology, Immunology, and Diagnostics. Content: The phylogenetic clustering of 95 SARS-CoV-2 sequences from the first 3 months of the pandemic reveals insights into the early evolution of the virus and gives first indications of how the variants are globally distributed. Variants might become a challenge in terms of diagnostics, immunology, and effectiveness of drugs. All available whole genome sequence data from the NCBI database (March 16, 2020) were phylogenetically analyzed, and gene prediction as well as analysis of selected variants were performed. Antigenic regions and the secondary protein structure were predicted for selected variants. While some clusters are presenting the same variant with 100% identical bases, other SARS-CoV-2 lineages show a beginning diversification and phylogenetic clustering due to base substitutions and deletions in the genomes. First molecular epidemiological investigations are possible with the results by adding metadata as travelling history to the presented data. The advantage of variants in source tracing can be a challenge in terms of virulence, immune response, and immunological memory. Variants of viruses often show differences in virulence or antigenicity. This must also be considered in decisions like herd immunity. Diagnostic methods might not work if the variations or deletions are in target regions for the detection of the pathogen. One base substitution was detected in a primer binding site.", "qid": 37, "docid": "3sxlvoxf", "rank": 29, "score": 12.933699607849121}, {"content": "Title: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 Content: Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of \u201cgenome-type clusters\u201d and adaptive selection of \u201cL\u201d type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the \u201cmajor group\u201d (52.2%) and the \u201cminor group\u201d (30.4%), harboring four and five co-existing mutations, respectively. The \u201cmajor group\u201d mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.", "qid": 37, "docid": "915srotp", "rank": 30, "score": 12.898300170898438}, {"content": "Title: A High-Coverage SARS-CoV-2 Genome Sequence Acquired by Target Capture Sequencing Content: This manuscript is based on the method we developed urgently to deal with the research requirement in the conflict between achieving a complete genome sequence for the evolutionary history of SARS-CoV-2 study and the low viral RNA concentration. Here, in this manuscript, we developed a set of SARS-CoV-2 enrichment probes to increase the sensitivity of sequence-based virus detection and characterization via obtaining the comprehensive genome sequence. Following the CDC health and safety guidelines, we test the concept using the culturing supernatant contain SARS-CoV-2 particles, and its full-length sequence was used for further analysis. The fraction of SARS-CoV-2 endogenous DNA was 93.47% with Cluster Factor about 1.1, which demonstrate that the numbers of mapped reads to SARS-CoV-2 reference sequence significantly increased, compared to metagenomic sequencing technology, following SARS-CoV-2 probe enrichment. Moreover, based on the high-quality sequence, we discussed the heterozygosity and viral expression during replication of coronavirus, and its phylogenetic relationship with other selected high-quality samples from The Genome Variation Map (GVM) (on 2020/03/22). We believe this manuscript is valuable for all the researchers who are interested in using clinical warp samples to obtain the high coverage of SARS-CoV-2 genome sequence with a relatively low concentration of viral particles. This would allow the clinician to correlate the diagnostic data with molecular monitoring in viral evolutional, the most importantly, to track the functional mutation of SARS-CoV-2.", "qid": 37, "docid": "yb6if23t", "rank": 31, "score": 12.881400108337402}, {"content": "Title: The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39). Content: The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5' RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.", "qid": 37, "docid": "myhlbq9h", "rank": 32, "score": 12.87559986114502}, {"content": "Title: Genome Analysis of SARS-CoV-2 Isolate from Bangladesh Content: Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.", "qid": 37, "docid": "gygi11gk", "rank": 33, "score": 12.852800369262695}, {"content": "Title: Phylogenetic analysis of the full\u2010length SARS\u2010CoV sequences: Evidence for phylogenetic discordance in three genomic regions Content: The origin of the severe acute respiratory syndrome\u2010coronavirus (SARS\u2010CoV) remains unclear. Evidence based on Bayesian scanning plots and phylogenetic analysis using maximum likelihood (ML) and Bayesian methods indicates that SARS\u2010CoV, for the largest part of the genome (\u223c80%), is more closely related to Group II coronaviruses sequences, whereas in three regions in the ORF1ab gene it shows no apparent similarity to any of the previously characterized groups of coronaviruses. There is discordant phylogenetic clustering of SARS\u2010CoV and coronaviruses sequences, throughout the genome, compatible with either ancient recombination events or altered evolutionary rates in different lineages, or a combination of both. J. Med. Virol. 74:369\u2013372, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.", "qid": 37, "docid": "arp07mck", "rank": 34, "score": 12.838399887084961}, {"content": "Title: Full genome viral sequences inform patterns of SARS-CoV-2 spread into and within Israel Content: Full genome sequences are increasingly used to track the geographic spread and transmission dynamics of viral pathogens. Here, with a focus on Israel, we sequenced 212 SARS-CoV-2 sequences and use them to perform a comprehensive analysis to trace the origins and spread of the virus. A phylogenetic analysis including thousands of globally sampled sequences allowed us to infer multiple independent introductions into Israel, followed by local transmission. Returning travelers from the U.S. contributed dramatically more to viral spread relative to their proportion in incoming infected travelers. Using phylodynamic analysis, we estimated that the basic reproduction number of the virus was initially around ~2.0-2.6, dropping by two-thirds following the implementation of social distancing measures. A comparison between reported and model-estimated case numbers indicated high levels of transmission heterogeneity in SARS-CoV-2 spread, with between 1-10% of infected individuals resulting in 80% of secondary infections. Overall, our findings underscore the ability of this virus to efficiently transmit between and within countries, as well as demonstrate the effectiveness of social distancing measures for reducing its spread.", "qid": 37, "docid": "dwd86zc3", "rank": 35, "score": 12.791600227355957}, {"content": "Title: [Analysis of variation and evolution of SARS-CoV-2 genome] Content: OBJECTIVE: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of \u00df Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "qid": 37, "docid": "fofy6whl", "rank": 36, "score": 12.732799530029297}, {"content": "Title: [Analysis of variation and evolution of SARS-CoV-2 genome]. Content: OBJECTIVE To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of \u03b2 Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "qid": 37, "docid": "h8abjsxr", "rank": 37, "score": 12.73279857635498}, {"content": "Title: Quantification of Intra-Host Genomic Diversity of SARS-CoV-2 Allows a High-Resolution Characterization of Viral Evolution and Reveals Functionally Convergent Variants Content: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. our approach accounts for accumulation of clonal mutations and uncertainty in the data, by taking advantage of the achievements of research in cancer evolution, to deliver robust phylogenomic lineage models, and exploits intra-host variant frequency profiles to characterize the sublineage similarity among samples, which may derive from uncovered infection events. The application of our approach to RNA-sequencing data of 162 SARS-CoV-2 samples generates a high-resolution model of evolution and spread, which improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, revealing likely infection paths among hosts harboring the same viral lineage. The in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and identifies a number of variants that are transiting from minor to clonal state in the population. We also show that standard phylogenetic methods can produce unreliable results when handling datasets with noise and sampling limitations, as proven by the further application of VERSO to 12419 consensus sequences included in GISAID database. Notably, VERSO allows to pinpoint minor variants that might be positively or negatively selected across distinct lineages, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on independent samples, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. Finally, we here release the likely SARS-CoV-2 ancestral genome, obtained by resolving ambiguous SNPs that distinguish two widely-used reference genomes from human samples, by employing the Pangolin-CoV and the Bat-CoV-RaTG13 genomes. Our results show that the joint application of our framework and data-driven epidemiological models might allow to deliver a high-resolution platform for pathogen surveillance and analysis.", "qid": 37, "docid": "ea78sjcs", "rank": 38, "score": 12.720999717712402}, {"content": "Title: Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology Content: Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.", "qid": 37, "docid": "8m06zdho", "rank": 39, "score": 12.694899559020996}, {"content": "Title: A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications Content: The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.", "qid": 37, "docid": "8vl0okiv", "rank": 40, "score": 12.674500465393066}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 37, "docid": "c5fygzvz", "rank": 41, "score": 12.65530014038086}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 37, "docid": "w5ytp1q7", "rank": 42, "score": 12.655299186706543}, {"content": "Title: Isolation and rapid sharing of the 2019 novel coronavirus (SARS\u2010CoV\u20102) from the first patient diagnosed with COVID\u201019 in Australia Content: OBJECTIVES: To describe the first isolation and sequencing of SARS\u2010CoV\u20102 in Australia and rapid sharing of the isolate. SETTING: SARS\u2010CoV\u20102 was isolated from a 58\u2010year\u2010old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID\u201019 (the illness caused by SARS\u2010CoV\u20102) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS\u2010CoV\u20102 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS\u2010CoV\u20102 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS\u2010CoV\u20102 genomes. Within 24 hours of isolation, the first Australian SARS\u2010CoV\u20102 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS\u2010CoV\u20102 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.", "qid": 37, "docid": "4w5o8jfu", "rank": 43, "score": 12.641500473022461}, {"content": "Title: Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia Content: OBJECTIVES: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. SETTING: SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.", "qid": 37, "docid": "wmfgodo6", "rank": 44, "score": 12.641499519348145}, {"content": "Title: Full genome sequence of the first SARS-CoV-2 detected in Mexico Content: SARS-CoV-2 was first detected in the city of Wuhan, Hubei Province, China. In this report, we describe the complete genome sequence of the first imported SARS-CoV-2, detected in a Mexican patient who had traveled to Bergamo, Italy. Phylogenetic analysis showed that this isolate belongs to subclade A2a (lineage G) and is closely related to isolates from Finland, Germany and Brazil, all of which were from patients with a history of travel to Italy. This is the first report of the complete genome sequence of this virus in Mexico.", "qid": 37, "docid": "oi2cm546", "rank": 45, "score": 12.632399559020996}, {"content": "Title: Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses Content: Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.", "qid": 37, "docid": "005b2j4b", "rank": 46, "score": 12.583399772644043}, {"content": "Title: Chasing the origin of SARS-CoV-2 in Canada\u2019s COVID-19 cases: A genomics study Content: The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.", "qid": 37, "docid": "8gtnbm1c", "rank": 47, "score": 12.560700416564941}, {"content": "Title: The Novel Coronavirus SARS\u2010CoV\u20102: From a Zoonotic Infection to Coronavirus Disease\u201019 (COVID19) Content: OBJECTIVE: The novel coronavirus, SARS\u2010CoV\u20102 is an international public health emergency. Until now, the intermediate host and mechanisms of interspecies jump of this virus are unknown. METHODS: Phylogenetic analysis of all available bat coronavirus (CoV) complete genomes was performed in order to analyze the relationships between bat CoV and SARS\u2010CoV\u20102. In order to suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals which were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions which may have permitted the adaptation of SARS\u2010CoV\u20102 to the human host. RESULTS: The phylogenetic analysis demonstrated that SARS\u2010CoV\u20102 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS\u2010CoV\u20102, bat RaTG13 and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS\u2010CoV\u20102 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS\u2010CoV\u20102 tropism to human cells. CONCLUSIONS: Our analysis shows the tight relationship between SARS\u2010CoV\u20102 and bat SARS\u2010like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function. This article is protected by copyright. All rights reserved.", "qid": 37, "docid": "4ze0mfxp", "rank": 48, "score": 12.53030014038086}, {"content": "Title: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization Content: We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain [1] project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM and via an interactive website at https://covid19-ism.coe.drexel.edu/. Author Summary The novel coronavirus responsible for COVID-19, SARS-CoV-2, expanded to reportedly 8.7 million confirmed cases worldwide by June 21, 2020. The global SARS-CoV-2 pandemic highlights the importance of tracking viral transmission dynamics in real-time. Through June 2020, researchers have obtained genetic sequences of SARS-CoV-2 from over 47,000 samples from infected individuals worldwide. Since the virus readily mutates, each sequence of an infected individual contains useful information linked to the individual\u2019s exposure location and sample date. But, there are over 30,000 bases in the full SARS-CoV-2 genome\u2014so tracking genetic variants on a whole-sequence basis becomes unwieldy. We describe a method to instead efficiently identify and label genetic variants, or \u201csubtypes\u201d of SARS-CoV-2. Applying this method results in a compact, 11 base-long compressed label, called an Informative Subtype Marker or \u201cISM\u201d. We define viral subtypes for each ISM, and show how regional distribution of subtypes track the progress of the pandemic. Major findings include (1) covarying nucleotides with the spike protein which has spread rapidly and (2) tracking emergence of a local subtype across the United States connected to Asia and distinct from the outbreak in New York, which is found to be connected to Europe.", "qid": 37, "docid": "9siu7wgs", "rank": 49, "score": 12.527700424194336}, {"content": "Title: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Content: BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99\u00b798% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.", "qid": 37, "docid": "mqduxqdl", "rank": 50, "score": 12.50730037689209}, {"content": "Title: SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East Content: Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.", "qid": 37, "docid": "b15befg1", "rank": 51, "score": 12.483699798583984}, {"content": "Title: SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East. Content: Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.", "qid": 37, "docid": "p47lhd25", "rank": 52, "score": 12.483698844909668}, {"content": "Title: Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world Content: Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.", "qid": 37, "docid": "tutit2bc", "rank": 53, "score": 12.434300422668457}, {"content": "Title: Genome-wide analysis of Indian SARS-CoV-2 genomes for the identification of genetic mutation and SNP Content: The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is build to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population.", "qid": 37, "docid": "lt0uo7q3", "rank": 54, "score": 12.428099632263184}, {"content": "Title: A48 Identification and full-genome characterization of Alpha- and Beta-Coronaviruses viruses from bats in Italy Content: Bats are the natural reservoir of Coronaviruses (CoVs). Human CoVs cause mild respiratory diseases worldwide, but, in the last decade, two Beta-CoVs [Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome] caused thousands of deaths and cases worldwide. Phylogenetic analysis suggested the evolutionary origin of mammalian CoVs is derived from bats. In this study, we characterized three Alpha-CoVs and two Beta-CoVs demonstrating the circulation of bat strains in Italy. Isolates were sequenced using a next-generation sequencing approach and genomes reconstructed using the online tool Galaxy Aries. Phylogenetic analyses were conducted using MEGA7 and MrBayes. Similarity plots were generated using SSE v1.2. The structure of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank. Bioinformatics analysis permitted the identification of 2 Beta-CoV complete genomes of 30 kb and three Alpha-CoV of 28 kb (named BatCoV-ITA1-5). BatCoV-ITA1 and 2 formed a monophyletic group with MERS-CoV sequences. The comparison of the concatenated domains within ORF1ab confirmed their classification into the MERS-CoV species. The 3D structure of RBD of Italian strains showed two amino acid deletions located in a region corresponding to the external subdomain of MERS-RBD. BatCoV-Ita3 and BatCoV-Ita4/5 were classified into two novel Alpha-CoV species by comparison of concatenated domains within ORF1ab. Due to the high divergence with the Alpha human spike protein strains, it was impossible to establish the protein structure and the potential affinity to human receptor. The Italian strains showed the typical organization of Alpha and Beta-CoVs. We reported two Beta-CoVs closely related to MERS-CoVs from bats belonging to common Italian species (Pipistrellus kuhlii and Hypsugo savii). The analysis of the RBD in the spike protein indicates significant differences from human RBD known to date. The three Alpha-CoV strains were classified into two novel species, confirming the high heterogeneity of CoV strains in bats. Although the studies conducted cannot confirm a risk for humans, surveillance studies are needed to investigate the genetic diversity of CoVs in bats. Because this exceeds what is known for other hosts, it is compatible with bats being the major reservoir of mammalian CoVs.", "qid": 37, "docid": "hb9leola", "rank": 55, "score": 12.372699737548828}, {"content": "Title: An Analysis of SARS-CoV-2 Using ViReport Content: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of cases and hundreds of thousands of deaths. Given the current lack of treatments or vaccines available, it may be useful to trace the evolu-tion and spread of the virus to better develop methods of preventative intervention. In this study, we analyzed over 4,000 full genome sequences of human SARS-CoV-2 using novel tool ViReport [13], an automated workflow for performing phylogenetic analyses on viral sequences and generating comprehensive molecular epidemiologi-cal reports. The complete ViReport output can be found at https://github.com/mirandajsong/ViReport-SARS-CoV-2.", "qid": 37, "docid": "whmawr4q", "rank": 56, "score": 12.354499816894531}, {"content": "Title: Genomic epidemiology of SARS-CoV-2 in Colombia Content: Coronavirus disease 2019 (COVID-19) was first diagnosed in Colombia from a traveler arriving from Italy on February 26, 2020. To date, available data on the origins and number or introductions of SARS-CoV-2 into the country are limited. Here, we sequenced SARS-CoV-2 from 43 clinical samples and-together with another 73 genomes sequences available from the country-we investigated the emergence and the routes of importation of COVID-19 into Colombia using epidemiological, historical air travel and phylogenetic observations. Our study provided evidence of multiple introductions, mostly from Europe, with at least 12 lineages being documented. Phylogenetic findings validated the linkage of epidemiologically-linked transmission chains. Our results demonstrate the advantages of genome sequencing to complement COVID-19 outbreak investigation and underscores that human mobility and genetic data are relevant to complete epidemiological investigation and better characterize virus transmission dynamics at local scales.", "qid": 37, "docid": "jm4bu1bf", "rank": 57, "score": 12.30780029296875}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "qid": 37, "docid": "vf32wxkx", "rank": 58, "score": 12.279500007629395}, {"content": "Title: The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities. Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the \"cytokine storm\" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.", "qid": 37, "docid": "0ydpwdpz", "rank": 59, "score": 12.272000312805176}, {"content": "Title: The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the \"cytokine storm\" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.", "qid": 37, "docid": "isikf6cj", "rank": 60, "score": 12.27199935913086}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov SUPPLEMENTARY INFORMATION:", "qid": 37, "docid": "st5idleq", "rank": 61, "score": 12.270000457763672}, {"content": "Title: Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2) Content: Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that the view, pangolin acted as an intermediate host, may be controversial. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximate 2 km), indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately concluded that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term and then leading to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019, which may indicated that the transmission could have begun from person to person in mid to late November.", "qid": 37, "docid": "fnj57b0l", "rank": 62, "score": 12.26830005645752}, {"content": "Title: Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. Content: UNLABELLED Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs. IMPORTANCE Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.", "qid": 37, "docid": "b5mvqb4p", "rank": 63, "score": 12.24839973449707}, {"content": "Title: SARS\u2010CoV\u20102: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein Content: To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS\u2010CoV\u20102, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS\u2010CoV\u20102 was more similar to the bats' betacoronavirus isolates: HKU5\u2010related from Pipistrellus abramus and HKU4\u2010related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS\u2010CoV\u20102, responsible for the current outbreak of COVID\u201019, could also come from yak as an intermediate host.", "qid": 37, "docid": "ayhsbfd1", "rank": 64, "score": 12.222900390625}, {"content": "Title: SARS-CoV-2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein Content: To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS-CoV-2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS-CoV-2 was more similar to the bats' betacoronavirus isolates: HKU5-related from Pipistrellus abramus and HKU4-related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS-CoV-2, responsible for the current outbreak of COVID-19, could also come from yak as an intermediate host.", "qid": 37, "docid": "d9qtn37b", "rank": 65, "score": 12.222899436950684}, {"content": "Title: Presence and vitality of SARS-CoV-2 virus in wastewaters and rivers Content: Wastewater-based epidemiology has been proposed to monitor the diffusion and trend of SARS-CoV-2 pandemic. In the present study, raw and treated samples from three wastewater treatment plants, and two river samples characterized the Milano Metropolitan Area, Italy, were surveyed for SARS-CoV-2 RNA positivity to real time PCR and infectiveness. Moreover, whole genome sequencing and phylogenetic analysis of isolated strains was performed. Raw wastewater samples resulted positive to PCR amplification, while treated water samples were always negative (four and two samples, respectively, sampled in two dates). Moreover, the rate of positivity in raw wastewater samples decreased after eight days, in congruence with the epidemiological trend estimated for the interested provinces. Virus infectiveness was always not significant, indicating the effectiveness of wastewater treatments, or the natural decay of viral vitality, which implied the absence of significant risk of infection from wastewaters. Samples from receiving rivers (two sites, sampled in the same dates as wastewaters) showed in some cases a positivity to PCR amplification, probably due to non-treated discharges, or the combined sewage overflows. Nevertheless, also for rivers vitality was negligible, indicating the absence of sanitary risks. Phylogenetic analysis of genome indicated that the isolated virus belongs to the most spread strain present in Europe and similar to another strain found in Lombardy.", "qid": 37, "docid": "qekpx2zy", "rank": 66, "score": 12.214699745178223}, {"content": "Title: SARS-CoV-2 Molecular and Phylogenetic analysis in COVID-19 patients: A preliminary report from Iran Content: BACKGROUND: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. METHODS: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. RESULTS: The mean age of the patients in the present study was 60.42 \u00b1 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. CONCLUSION: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.", "qid": 37, "docid": "jhlnwoml", "rank": 67, "score": 12.207599639892578}, {"content": "Title: SARS-CoV-2 molecular and phylogenetic analysis in COVID-19 patients: A preliminary report from Iran. Content: BACKGROUND The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. METHODS We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. RESULTS The mean age of the patients in the present study was 60.42 \u00b1 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. CONCLUSION As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.", "qid": 37, "docid": "mjxs395h", "rank": 68, "score": 12.207598686218262}, {"content": "Title: Snapshot of the evolution and mutation patterns of SARS-CoV-2 Content: The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.", "qid": 37, "docid": "5od0tegt", "rank": 69, "score": 12.19159984588623}, {"content": "Title: Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States Content: Summary The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.", "qid": 37, "docid": "bakwk4tm", "rank": 70, "score": 12.179300308227539}, {"content": "Title: Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States Content: The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.", "qid": 37, "docid": "y3lr8obh", "rank": 71, "score": 12.179299354553223}, {"content": "Title: First detection and genome sequencing of SARS-CoV-2 in an infected cat in France Content: After its first description in Wuhan (China), SARS-CoV-2 the agent of coronavirus disease 2019 (COVID-19) rapidly spread worldwide. Previous studies suggested that pets could be susceptible to SARS-CoV-2. Here, we investigated the putative infection by SARS-CoV-2 in 22 cats and 11 dogs from owners previously infected or suspected of being infected by SARS-CoV-2. For each animal, rectal, nasopharyngeal swabs and serum were taken. Swabs were submitted to RT-qPCR assays targeting 2 genes of SARS-CoV-2. All dogs were tested SARS-CoV-2 negative. One cat was tested positive by RT-qPCR on rectal swab. Nasopharyngeal swabs from this animal were tested negative. This cat showed mild respiratory and digestive signs. Serological analysis confirms the presence of antibodies against the SARS-CoV-2 in both serum samples taken 10 days apart. Genome sequence analysis revealed that the cat SARS-CoV-2 belongs to the phylogenetic clade A2a like most of the French human SARS-CoV-2. This study reports for the first time the natural infection of a cat in France (near Paris) probably through their owners. There is currently no evidence that cats can spread COVID-19 and owners should not abandon their pets or compromise their welfare.", "qid": 37, "docid": "m5fcayl1", "rank": 72, "score": 12.15820026397705}, {"content": "Title: First detection and genome sequencing of SARS\u2010CoV\u20102 in an infected cat in France Content: After its first description in Wuhan (China), SARS\u2010CoV\u20102 the agent of coronavirus disease 2019 (COVID\u201019) rapidly spread worldwide. Previous studies suggested that pets could be susceptible to SARS\u2010CoV\u20102. Here, we investigated the putative infection by SARS\u2010CoV\u20102 in 22 cats and 11 dogs from owners previously infected or suspected of being infected by SARS\u2010CoV\u20102. For each animal, rectal, nasopharyngeal swabs and serum were taken. Swabs were submitted to RT\u2010qPCR assays targeting 2 genes of SARS\u2010CoV\u20102. All dogs were tested SARS\u2010CoV\u20102 negative. One cat was tested positive by RT\u2010qPCR on rectal swab. Nasopharyngeal swabs from this animal were tested negative. This cat showed mild respiratory and digestive signs. Serological analysis confirms the presence of antibodies against the SARS\u2010CoV\u20102 in the both serum samples taken 10 days apart. Genome sequence analysis revealed that the cat SARS\u2010CoV\u20102 belongs to the phylogenetic clade A2a like most of the French human SARS\u2010CoV\u20102. This study reports for the first time the natural infection of a cat in France (near Paris) probably through their owners. There is currently no evidence that cats can spread COVID\u201019 and owners should not abandon their pets or compromise their welfare.", "qid": 37, "docid": "o4y157hb", "rank": 73, "score": 12.158199310302734}, {"content": "Title: The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019 Content: The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.", "qid": 37, "docid": "5qn5h7p5", "rank": 74, "score": 12.139300346374512}, {"content": "Title: Comparative Analysis of SARS-CoV2 with Special Emphasis on Genome Sequences Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2), was declared a global pandemic on 11th March, 2020 by World Health Organization As of now,27th May,2020, there are about 54,88,825 infected cases and 3,49,095 deaths globally Coronavirus samples collected from all the countries have been sequenced for advanced studies in a bid to understand the structure and functioning of the virus In our study we have tried working on every available sequence to setup both comparisons and co-relations There is no such available study as of now for reference and hence it can become a pioneer stone in this direction The mortality rate calculated turns out to be 9 19%,34 37% and 6 29% for SARS-2003, MERS-2012 and COVID-19 respectively The basic reproduction rate R0 was 2-5 for SARS-2003, 0 3-0 8 for MERS-2012 and 1 4-5 7 for COVID-19 We found out the relation between number of mutations and mortality as well as phylogenetic relations High number of mutations corresponded to higher mortality rate as in countries like Italy and Spain Alpha and Beta-coronaviruses show a common ancestor from which they descended Brazil and Iran have shown similar phylogenetic descent explaining their mortality rate India however showed a distant relation from the common ancestor of other genome sequences This study highlights the mutations of the SARS-CoV2 virus as well as sets up a comparison with the previous outbreaks Similar type of studies should be conducted when more genome samples are present These results can also contribute towards making an effective anti-viral therapy and vaccines", "qid": 37, "docid": "chnj2ojk", "rank": 75, "score": 12.135700225830078}, {"content": "Title: Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses Content: In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed -1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "qid": 37, "docid": "dbem6cfo", "rank": 76, "score": 12.132100105285645}, {"content": "Title: Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses Content: Abstract In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed \u22121 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "qid": 37, "docid": "zaxjj9q7", "rank": 77, "score": 12.132099151611328}, {"content": "Title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes Content: SUMMARY: Genome detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next-generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present the Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2000 sequences per submission and the analysis of a new whole-genome sequence will take approximately 1 min. The tool has been tested and validated with hundreds of whole genomes from 10 coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY AND IMPLEMENTATION: https://www.genomedetective.com/app/typingtool/cov. CONTACT: koen@emweb.be or deoliveira@ukzn.ac.za. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "qid": 37, "docid": "88hswyln", "rank": 78, "score": 12.11709976196289}, {"content": "Title: Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China Content: Highlights: 1) 1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020; 2) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. 3) Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. 4) Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary: COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.", "qid": 37, "docid": "ju9japd8", "rank": 79, "score": 12.103799819946289}, {"content": "Title: Genomics of Indian SARS-CoV-2: Implications in genetic diversity, possible origin and spread of virus Content: World Health Organization (WHO) declared COVID-19 as a pandemic disease on March 11, 2020. Comparison of genome sequences from diverse locations allows us to identify the genetic diversity among viruses which would help in ascertaining viral virulence, disease pathogenicity, origin and spread of the SARS-CoV-2 between countries. The aim of this study is to ascertain the genetic diversity among Indian SARS-CoV-2 isolates. Initial examination of the phylogenetic data of SARS-CoV-2 genomes (n=3123) from different continents deposited at GISAID (Global Initiative on Sharing All Influenza Data) revealed multiple origin for Indian isolates. An in-depth analysis of 449 viral genomes derived from samples representing countries from USA, Europe, China, East Asia, South Asia, Oceania, Middle East regions and India revealed that most Indian samples are divided into two clusters (A and B) with cluster A showing more similarity to samples from Oceania and Kuwait and the cluster B grouping with countries from Europe, Middle East and South Asia. Diversity analysis of viral clades, which are characterized by specific non-synonymous mutations in viral proteins, discovered that the cluster A Indian samples belong to I clade (V378I in ORF1ab), which is an Oceania clade with samples having Iran connections and the cluster B Indian samples belong to G clade (D614G in Spike protein), which is an European clade. Thus our study identifies that the Indian SARS-CoV-2 viruses belong to I and G clades with potential origin to be countries mainly from Oceania, Europe, Middle East and South Asia regions, which strongly implying the spread of virus through most travelled countries. The study also emphasizes the importance of pathogen genomics through phylogenetic analysis to discover viral genetic diversity and understand the viral transmission dynamics with eventual grasp on viral virulence and disease pathogenesis.", "qid": 37, "docid": "i758v1vb", "rank": 80, "score": 12.093600273132324}, {"content": "Title: Genomic epidemiology of SARS-CoV-2 spread in Scotland highlights the role of European travel in COVID-19 emergence Content: Abstract SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China in December 2019 and spread rapidly throughout the world. Understanding the introductions of this new coronavirus in different settings may assist control efforts and the establishment of frameworks to support rapid response in future infectious disease outbreaks. We investigated the first four weeks of emergence of the SARS-CoV-2 virus in Scotland after the first case reported on the 1st March 2020. We obtained full genome sequences from 452 individuals with a laboratory-confirmed diagnosis of COVID-19, representing 20% of all cases until 1st April 2020 (n=2310). This permitted a genomic epidemiology approach to study the introductions and spread of the SARS-2 virus in Scotland. From combined phylogenetic and epidemiological analysis, we estimated at least 113 introductions of SARS-CoV-2 into Scotland during this period. Clusters containing multiple sequences suggestive of onward transmission occurred in 48/86 (56%). 42/86 (51%) clusters had no known international travel history indicating undetected introductions. The majority of viral sequences were most closely related to those circulating in other European countries, including Italy, Austria and Spain. Travel-associated introductions of SARS-CoV-2 into Scotland predated travel restrictions in the UK and other European countries. The first local transmission occurred three days after the first case. A shift from travel-associated to sustained community transmission was apparent after only 11 days. Undetected introductions occurred prior to the first known case of COVID-19. Earlier travel restrictions and quarantine measures might have resulted in fewer introductions into Scotland, thereby reducing the number of cases and the subsequent burden on health services. The high number of introductions and transmission rates were likely to have impacted on national contact tracing efforts. Our results also demonstrate that local real-time genomic epidemiology can be used to monitor transmission clusters and facilitate control efforts to restrict the spread of COVID-19.", "qid": 37, "docid": "bxuwx1jj", "rank": 81, "score": 12.090800285339355}, {"content": "Title: A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology Content: The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.", "qid": 37, "docid": "l7ymcyw7", "rank": 82, "score": 12.05049991607666}, {"content": "Title: The establishment of reference sequence for SARS\u2010CoV\u20102 and variation analysis Content: Starting around December 2019, an epidemic of pneumonia, which was named COVID\u201019 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full\u2010length genomic sequences of SARAS\u2010CoV\u20102 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS\u2010CoV\u20102 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%\u2010100%) at the nucleotide level and 99.99% (99.79%\u2010100%) at the amino acid level. Although overall variation in open\u2010reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS\u2010COV\u20102, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS\u2010CoV\u20102 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS\u2010CoV\u20102 infection in the future.", "qid": 37, "docid": "41ogljo8", "rank": 83, "score": 12.028400421142578}, {"content": "Title: The establishment of reference sequence for SARS-CoV-2 and variation analysis Content: Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.", "qid": 37, "docid": "g1zxlaer", "rank": 84, "score": 12.028399467468262}, {"content": "Title: Close relationship between SARS-coronavirus and group 2 coronavirus. Content: The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV.", "qid": 37, "docid": "ax6v6ham", "rank": 85, "score": 12.014599800109863}, {"content": "Title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum Content: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.", "qid": 37, "docid": "8871aifz", "rank": 86, "score": 12.008199691772461}, {"content": "Title: Insights into The Codon Usage Bias of 13 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Isolates from Different Geo-locations Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 (COVID-19) which is an infectious disease that spread throughout the world and was declared as a pandemic by the World Health Organization (WHO). In the present study, we analyzed genome-wide codon usage patterns in 13 SARS-CoV-2 isolates from different geo-locations (countries) by utilizing different CUB measurements. Nucleotide and di-nucleotide compositions displayed bias toward A/U content in all codon positions and CpU-ended codons preference, respectively. Relative Synonymous Codon Usage (RSCU) analysis revealed 8 common putative preferred codons among all the 13 isolates. Interestingly, all of the latter codons are A/U-ended (U-ended: 7, A-ended: 1). Cluster analysis (based on RSCU values) was performed and showed comparable results to the phylogenetic analysis (based on their whole genome sequences) indicating that the CUB pattern may reflect the evolutionary relationship between the tested isolates. To investigate the force (mutation and/or selection) influencing the pattern of CUB in SARS-CoV-2 coding sequences, we employed the following; (i). Effective number of codons (ENc), (ii). ENc-GC3 plot, (iii). Neutrality plot, and (iv) Codon adaptation index (CAI). According to their results, natural selection and/or other factors (not investigated in this study) may be the dominant force driving SARS-CoV-2 CUB. It is also worth mentioning that, by using the most expressed genes in human lung tissues as a reference set, some viral genes such as Nucleocapsid phosphoprotein, ORF7a protein, and surface glycoprotein had high CAI values which may indicate for selection force acting on their codon usage, as they play important roles in viral assembly and may help viruses avoid the host immune system. The outcome of our study may help in understanding the underlying factors involved in the evolution of SARS-CoV-2 viruses, and the interactions with their host. Also, it may aid in vaccine design strategies.", "qid": 37, "docid": "ooj9yqbx", "rank": 87, "score": 11.989100456237793}, {"content": "Title: Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide Content: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "qid": 37, "docid": "zu46bdpu", "rank": 88, "score": 11.972999572753906}, {"content": "Title: Companion vaccine Bioinformatic design tool reveals limited functional genomic variability of SARS-Cov-2 Spike Receptor Binding Domain Content: Tracking the genetic variability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for several reasons, such as to identify target sequences to generate robust vaccines and neutralizing monoclonal antibodies; to track viral genetic temporal and geographic evolution; and to mine for viral variants associated with reduced or increased severity. Several online tools and bioinformatic analyses have been released for this purpose; four main viral clades have been described via phylogenetic analyses. Here, we present an open-source bioinformatic protocol focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Results on the whole GISAID sequence dataset at the time of the writing (April\u2013June 2020) confirms no high variability pressure on the viral genome in terms of quality and quantity of mutations. We then focused our analysis on the receptor-binding domain region of the spike protein and only found a few variants associated with particular geographic locations that should be tracked over time. Finally, additional immunogenomic analyses revealed some variation in mutated epitope MHC compatibility and T-cell recognition for most frequent human HLAs.", "qid": 37, "docid": "thwnmobo", "rank": 89, "score": 11.964900016784668}, {"content": "Title: Comparing library preparation methods for SARS-CoV-2 multiplex amplicon sequencing on the Illumina MiSeq platform Content: Genomic surveillance has a key role in tracking the ongoing COVID-19 pandemic, but information on how different sequencing library preparation approaches affect the data produced are lacking. We compared three library preparation methods using both tagmentation (Nextera XT and Nextera Flex) and ligation-based (KAPA HyperPrep) approaches on both positive and negative samples to provide insights into any methodological differences between the methods, and validate their use in SARS-CoV-2 amplicon sequencing. We show that all three library preparation methods allow us to recover near-complete SARS-CoV-2 genomes with identical SNP calls. The Nextera Flex and KAPA library preparation methods gave better coverage than libraries prepared with Nextera XT, which required more reads to call the same number of genomic positions. The KAPA ligation-based approach shows the lowest levels of human contamination, but contaminating reads had no effect on the downstream analysis. We found some examples of library preparation-specific differences in minority variant calling. Overall our data shows that the choice of Illumina library preparation method has minimal effects on consensus base calling and downstream phylogenetic analysis, and suggests that all methods would be suitable for use if specific reagents are difficult to obtain.", "qid": 37, "docid": "2qk9pdbf", "rank": 90, "score": 11.94159984588623}, {"content": "Title: In-silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs Content: Recently a novel coronavirus (SARS-CoV-2) emerged from Wuhan, China and has infected more than 571000 people leading to more than 26000 deaths. Since SARS-CoV-2 genome sequences show similarity with those of SARS, we sought to analyze all the available SARS-CoV-2 genomes based on the insights obtained from SARS genome specifically focusing on non-coding RNAs. Here, results are presented from the dual approach i.e identifying host encoded miRNAs that might regulate viral pathogenesis as well as identifying viral encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing first approach resulted in the identification of 10 host encoded miRNAs that could target the genome of both the viruses (SARS-CoV-2 and SARS reference genome). Interestingly our analysis revealed that there is significantly higher number of host miRNAs that could target SARS-CoV-2 genome as compared to the SARS reference genome. Results from second approach involving SARS-CoV-2 and SARS reference genome identified a set of virus encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar \u201cGA\u201d rich motif in SARS-CoV-2 genome that was shown to play a vital role in lung pathogenesis during severe SARS infections. Hence, we successfully identified human and virus encoded miRNAs that might regulate pathogenesis of both these coronaviruses and the fact that more number of host miRNAs could target SARS-CoV-2 genomes possibly reveal as to why this virus follows mild pathogenesis in healthy individuals. We identified non-coding sequences in SARS-CoV-2 genomes that were earlier reported to contribute towards SARS pathology. The study provides insights into the overlapping sequences among these viruses for their effective inhibition as well as identifying new drug targets that could be used for development of new antivirals.", "qid": 37, "docid": "vj86lgri", "rank": 91, "score": 11.928600311279297}, {"content": "Title: Multiple SARS-CoV-2 introductions shaped the early outbreak in Central Eastern Europe: comparing Hungarian data to a worldwide sequence data-matrix Content: Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019 the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of the 21th of April, 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.", "qid": 37, "docid": "cg9pyoam", "rank": 92, "score": 11.854700088500977}, {"content": "Title: Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India Content: Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.", "qid": 37, "docid": "lhoks3ds", "rank": 93, "score": 11.849800109863281}, {"content": "Title: Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India. Content: Background & objectives : Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods : Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results : Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions : This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.", "qid": 37, "docid": "rdfch63j", "rank": 94, "score": 11.849799156188965}, {"content": "Title: The relationship of severe acute respiratory syndrome coronavirus with avian and other coronaviruses. Content: In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in humans in Guangdong Province, China, and caused an epidemic that had severe impact on public health, travel, and economic trade. Coronaviruses are worldwide in distribution, highly infectious, and extremely difficult to control because they have extensive genetic diversity, a short generation time, and a high mutation rate. They can cause respiratory, enteric, and in some cases hepatic and neurological diseases in a wide variety of animals and humans. An enormous, previously unrecognized reservoir of coronaviruses exists among animals. Because coronaviruses have been shown, both experimentally and in nature, to undergo genetic mutations and recombination at a rate similar to that of influenza viruses, it is not surprising that zoonosis and host switching that leads to epidemic diseases have occurred among coronaviruses. Analysis of coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal reservoir. Scientists examining coronavirus isolates from a variety of animals in and around Guangdong Province reported that SARS-CoV has similarities with many different coronaviruses including avian coronaviruses and SARS-CoV-like viruses from a variety of mammals found in live-animal markets. Although a SARS-like coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a lack of genomic sequences for the animal coronaviruses has prevented elucidation of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5' polymerase gene has a mammalian ancestry; whereas the 3' end structural genes (excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the host cell attachment viral surface protein, was shown to be a mosaic of feline coronavirus and avian coronavirus sequences resulting from a recombination event. Based on phylogenetic analysis designed to elucidate evolutionary links among viruses, SARS-CoV is believed to have branched from the modern Group 2 coronaviruses, suggesting that it evolved relatively rapidly. This is significant because SARS-CoV is likely still circulating in an animal reservoir (or reservoirs) and has the potential to quickly emerge and cause a new epidemic.", "qid": 37, "docid": "8z0ti0dx", "rank": 95, "score": 11.849100112915039}, {"content": "Title: Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco Content: COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "qid": 37, "docid": "zb1pzdd0", "rank": 96, "score": 11.835800170898438}, {"content": "Title: Introductions and early spread of SARS-CoV-2 in France Content: Following the emergence of coronavirus disease (COVID-19) in Wuhan, China in December 2019, specific COVID-19 surveillance was launched in France on January 10, 2020. Two weeks later, the first three imported cases of COVID-19 into Europe were diagnosed in France. We sequenced 97 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from samples collected between January 24 and March 24, 2020 from infected patients in France. Phylogenetic analysis identified several early independent SARS-CoV-2 introductions without local transmission, highlighting the efficacy of the measures taken to prevent virus spread from symptomatic cases. In parallel, our genomic data reveals the later predominant circulation of a major clade in many French regions, and implies local circulation of the virus in undocumented infections prior to the wave of COVID-19 cases. This study emphasizes the importance of continuous and geographically broad genomic sequencing and calls for further efforts with inclusion of asymptomatic infections.", "qid": 37, "docid": "gyr8k4j2", "rank": 97, "score": 11.826199531555176}, {"content": "Title: Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.", "qid": 37, "docid": "z14rf85c", "rank": 98, "score": 11.774200439453125}, {"content": "Title: SARS-CoV-2 spread across the Colombian-Venezuelan border Content: Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuelan ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region. We sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages Pangolin tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference. We found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. An additional three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome. Conclusions: Genomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region.", "qid": 37, "docid": "umoowoa2", "rank": 99, "score": 11.732999801635742}, {"content": "Title: Wild animal surveillance for coronavirus HKU1 and potential variants of other coronaviruses. Content: 1. Although CoV-HKU1 was not identified in any of the studied animals, a coronavirus closely related to SARS-CoV (bat-SARS-CoV) was identified in 23 (19%) of 118 wild Chinese horseshoe bats by reverse transcriptase polymerase chain reaction (RT-PCR). 2. Complete genome sequencing and phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b coronaviruses, distantly related to known group 2 coronaviruses. 3. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike gene. The presence of a29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. 4. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats using an enzyme immunoassay.Neutralising antibody to human SARS-CoV was also detected in those with lower viral loads.5. This study also revealed a previously unknown diversity of coronaviruses in bats, which are important natural reservoir for coronaviruses including SARS-CoV-like viruses.", "qid": 37, "docid": "ere58jal", "rank": 100, "score": 11.72249984741211}]}
{"query": "What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases?", "hits": [{"content": "Title: Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy? Content: In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In \"chronic inflammatory diseases\", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.", "qid": 38, "docid": "xhr9i6gw", "rank": 1, "score": 9.871999740600586}, {"content": "Title: COVID-19 Hyperinflammation: What about Neutrophils? Content: COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.", "qid": 38, "docid": "9l5ajo4q", "rank": 2, "score": 9.845000267028809}, {"content": "Title: A dynamic immune response shapes COVID-19 progression Content: The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic Patient throat swabs were tested daily for SARS-CoV-2 with the virus persisting for 3-4 weeks in all three patients Cytokine analyses of whole blood revealed increased cytokine expression in the single more severe case However, most inflammatory gene expression peaked after respiratory function nadir, except those in the IL1 pathway Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T-cell activation that could exacerbate disease or prolong the infection Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19 This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies", "qid": 38, "docid": "uxehz43v", "rank": 3, "score": 9.840800285339355}, {"content": "Title: A Dynamic Immune Response Shapes COVID-19 Progression Content: The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.", "qid": 38, "docid": "xm0n9iu4", "rank": 4, "score": 9.840799331665039}, {"content": "Title: Dupilumab and COVID\u201019: What should we expect? Content: Coronavirus disease 2019 (COVID\u201019) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL\u20104 and IL\u201013, used for adult atopic dermatitis. The pathogenesis of COVID\u201019 is complex, characterized by an immune response mainly Th1/Th17. The hyper\u2010activation of these cells may cause the release of pro\u2010inflammatory cytokines that may result in lung impairment. IL\u20104 and IL\u201013 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID\u201019 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID\u201019.", "qid": 38, "docid": "7i6wnto5", "rank": 5, "score": 9.668000221252441}, {"content": "Title: Dupilumab and COVID-19: What should we expect? Content: Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL-4 and IL-13, used for adult atopic dermatitis. The pathogenesis of COVID-19 is complex, characterized by an immune response mainly Th1/Th17. The hyper-activation of these cells may cause the release of pro-inflammatory cytokines that may result in lung impairment. IL-4 and IL-13 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID-19 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID-19.", "qid": 38, "docid": "rn1t7612", "rank": 6, "score": 9.667999267578125}, {"content": "Title: Inflammatory and Coagulative Considerations for the Management of Orthopaedic Trauma Patients With COVID-19: A Review of the Current Evidence and Our Surgical Experience Content: Mounting evidence suggests that the pathogenesis of coronavirus disease 2019 (COVID-19) involves a hyperinflammatory response predisposing patients to thromboembolic disease and acute respiratory distress. In the setting of severe blunt trauma, damaged tissues induce a local and systemic inflammatory response through similar pathways to COVID-19. As such, patients with COVID-19 sustaining orthopaedic trauma injuries may have an amplified response to the traumatic insult because of their baseline hyperinflammatory and hypercoagulable states. These patients may have compromised physiological reserve to withstand the insult of surgical intervention before reaching clinical instability. In this article, we review the current evidence regarding pathogenesis of COVID-19 and its implications on the management of orthopaedic trauma patients by discussing a case and the most recent literature.", "qid": 38, "docid": "41gth6o0", "rank": 7, "score": 9.265399932861328}, {"content": "Title: Inflammatory and Coagulative Considerations for the Management of Orthopaedic Trauma Patients with COVID-19: A Review of the Current Evidence and Our Surgical Experience Content: Mounting evidence suggests that the pathogenesis of coronavirus disease 2019 (COVID-19) involves a hyperinflammatory response predisposing patients to thromboembolic disease and acute respiratory distress. In the setting of severe blunt trauma, damaged tissues induce a local and systemic inflammatory response through similar pathways to COVID-19. As such, patients with COVID-19 sustaining orthopaedic trauma injuries may have an amplified response to the traumatic insult due to their baseline hyperinflammatory and hypercoagulable state. These patients may have compromised physiological reserve to withstand the insult of surgical intervention before reaching clinical instability. Herein, we review the current evidence regarding pathogenesis of COVID-19 and its implications on the management of orthopaedic trauma patients by discussing a case and the most recent literature.", "qid": 38, "docid": "ldjqczvr", "rank": 8, "score": 9.265398979187012}, {"content": "Title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms Content: At the end of 2019, the entire world has witnessed the birth of a new member of coronavirus family in Wuhan, China. Ever since, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has swiftly invaded every corner on the planet. By the end of April 2020, almost 3.5 million cases have been reported worldwide, with a death toll of about 250000 deaths. It is currently well-recognized that patient\u2019s immune response plays a pivotal role in the pathogenesis of Coronavirus Disease 2019 (COVID-19). This inflammatory element was evidenced by its elevated mediators that, in severe cases, reach their peak in a cytokine storm. Together with the reported markers of liver injury, such hyperinflammatory state may trigger significant derangements in hepatic cytochrome P450 metabolic machinery, and subsequent modulation of drug clearance that may result in unexpected therapeutic/toxic response. We hypothesize that COVID-19 patients are potentially vulnerable to a significant disease-drug interaction, and therefore, suitable dosing guidelines with therapeutic drug monitoring should be implemented to assure optimal clinical outcomes.", "qid": 38, "docid": "v95pf3eg", "rank": 9, "score": 9.081899642944336}, {"content": "Title: Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019. Content: Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "qid": 38, "docid": "1zq0aels", "rank": 10, "score": 9.071599960327148}, {"content": "Title: Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019 Content: Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "qid": 38, "docid": "5ad4rm3y", "rank": 11, "score": 9.071599006652832}, {"content": "Title: COVID\u201019: a collision of complement, coagulation and inflammatory pathways Content: COVID\u201019 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical ARDS seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical haemolytic uraemic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID\u201019, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5 respectively. C5a is a potent cell signalling protein that activates a cytokine storm \u2013 a hyper\u2010inflammatory phenomenon \u2013 within hours of infection and the innate immune response. However, excess C5a can result in a pro\u2010inflammatory environment orchestrated through a plethora of mechanisms, that propagates lung injury, lymphocyte exhaustion and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro\u2010coagulant state in the microvasculature of critical organs. Fatal COVID\u201019 has been associated with a systemic inflammatory response accompanied by a pro\u2010coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID\u201019. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID\u201019.", "qid": 38, "docid": "gkjb1y83", "rank": 12, "score": 9.025899887084961}, {"content": "Title: COVID-19: a collision of complement, coagulation and inflammatory pathways Content: COVID-19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical ARDS seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical haemolytic uraemic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID-19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5 respectively. C5a is a potent cell signalling protein that activates a cytokine storm - a hyper-inflammatory phenomenon - within hours of infection and the innate immune response. However, excess C5a can result in a pro-inflammatory environment orchestrated through a plethora of mechanisms, that propagates lung injury, lymphocyte exhaustion and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro-coagulant state in the microvasculature of critical organs. Fatal COVID-19 has been associated with a systemic inflammatory response accompanied by a pro-coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID-19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19.", "qid": 38, "docid": "oj0zthe9", "rank": 13, "score": 9.025898933410645}, {"content": "Title: Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state. Content: For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.", "qid": 38, "docid": "e445bj0e", "rank": 14, "score": 8.935999870300293}, {"content": "Title: Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state Content: For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.", "qid": 38, "docid": "li7f5x0g", "rank": 15, "score": 8.935998916625977}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 38, "docid": "fqlv35vo", "rank": 16, "score": 8.9350004196167}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 38, "docid": "iaatjew2", "rank": 17, "score": 8.934999465942383}, {"content": "Title: Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections Content: Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by viral infections is less prevalent in the literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphaviruses and flaviviruses.", "qid": 38, "docid": "qjpownkg", "rank": 18, "score": 8.925100326538086}, {"content": "Title: Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins Content: Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.", "qid": 38, "docid": "rs0dj55s", "rank": 19, "score": 8.754799842834473}, {"content": "Title: Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases? Content: BACKGROUND: COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a \u201ccytokine storm\u201d). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure. MAIN TEXT: The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection. CONCLUSION: The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.", "qid": 38, "docid": "x1g9u1j2", "rank": 20, "score": 8.703800201416016}, {"content": "Title: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract Content: Abstract MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1\u03b1 and IL-1\u03b2 and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.", "qid": 38, "docid": "ku4z34lu", "rank": 21, "score": 8.649700164794922}, {"content": "Title: Severe COVID-19: A Review of Recent Progress With a Look Toward the Future Content: The novel coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the World Health Organization has confirmed that COVID-19 is a global infectious disease pandemic. This is the third acute infectious disease caused by coronavirus infection in this century, after sudden acute respirator syndrome and Middle East respiratory syndrome. The damage mechanism of SARS-CoV-2 is still unclear. It is possible that protein S binds to angiotensin-converting enzyme 2 receptors and invades alveolar epithelial cells, causing direct toxic effects and an excessive immune response. This stimulates a systemic inflammatory response, thus forming a cytokine storm, which leads to lung tissue injury. In severe cases, the disease can lead to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Patients with severe COVID-19 have a relatively high mortality rate. Currently, there are no specific antiviral drugs for the treatment of COVID-19. Most patients need to be admitted to the intensive care unit for intensive monitoring and supportive organ function treatments. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment methods of severe COVID-19 and puts forward some tentative ideas, aiming to provide some guidance for the diagnosis and treatment of severe COVID-19.", "qid": 38, "docid": "lyx7mnnz", "rank": 22, "score": 8.63539981842041}, {"content": "Title: Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis Content: The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-\u041aB repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.", "qid": 38, "docid": "zbp8jzbe", "rank": 23, "score": 8.599100112915039}, {"content": "Title: Suppressive myeloid cells are a hallmark of severe COVID-19 Content: 'Severe Acute Respiratory Syndrome - Coronavirus-2' (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46 + n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DR high CD11c high inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DR low monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.", "qid": 38, "docid": "8qml9rrb", "rank": 24, "score": 8.536600112915039}, {"content": "Title: Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic Content: Coronavirus disease-2019 (COVID-19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin-converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS-CoV-2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS-CoV-2 in COVID-19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID-19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS-CoV-2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.", "qid": 38, "docid": "dnjsohzk", "rank": 25, "score": 8.500900268554688}, {"content": "Title: Hyperglycemia, hydroxychloroquine, and the COVID\u201019 pandemic Content: Coronavirus disease\u20102019 (COVID\u201019) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102) viral particles in the lung epithelium, the concentration of glycosylated angiotensin\u2010converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS\u2010CoV\u20102 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS\u2010CoV\u20102 in COVID\u201019 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID\u201019 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS\u2010CoV\u20102 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.", "qid": 38, "docid": "ub7s6yz6", "rank": 26, "score": 8.500899314880371}, {"content": "Title: The Heart and COVID-19: What Cardiologists Need to Know. Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 38, "docid": "7icw3be3", "rank": 27, "score": 8.490799903869629}, {"content": "Title: Inflammation: A bridge between Diabetes and COVID-19, and possible management with sitagliptin Content: Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.", "qid": 38, "docid": "8p5chz08", "rank": 28, "score": 8.431599617004395}, {"content": "Title: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.", "qid": 38, "docid": "etaa9a1v", "rank": 29, "score": 8.383299827575684}, {"content": "Title: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS: Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.", "qid": 38, "docid": "ou7hpqjd", "rank": 30, "score": 8.383298873901367}, {"content": "Title: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes Content: SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30\u201350,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.", "qid": 38, "docid": "f783oobv", "rank": 31, "score": 8.381999969482422}, {"content": "Title: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes Content: SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30-50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.", "qid": 38, "docid": "l9f7g2l4", "rank": 32, "score": 8.381999015808105}, {"content": "Title: O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ The Heart and COVID-19: What Cardiologists Need to Know Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 38, "docid": "tp2tm0vn", "rank": 33, "score": 8.345100402832031}, {"content": "Title: A Case of Cytokine Hemofiltration and ECLS as Treatment of COVID-19 Respiratory Failure Content: Abstract Background Discovery of the novel severe acute respiratory syndrome coronavirus 2 (n-SARS-CoV-2) in late 2019 has brought with it a renewed interest in methods of inflammatory mitigation, particularly due to reports of a cytokine release syndrome playing a pathogenic role [1]. One method of decreasing inflammation is through hemofiltration in combination with a dialysis membrane that has a large cutoff for protein permeability (high-cutoff/HCO), thereby capturing inflammatory cytokines and attenuating their harmful side effects. The authors report a patient with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 infection, requiring Veno-Venous Extracorporeal Life Support (VV-ECLS) who was treated with cytokine hemofiltration and showed clinical improvement. Case Summary Our patient is a 53 year-old female who presented with coronavirus infection and respiratory failure culminating in hypoxemia refractory to conventional mechanical ventilation. She was cannulated onto veno-venous extra-corporeal life support and treated with cytokine hemofiltration using a high-cutoff filter. Following treatment, inflammatory markers improved along with compliance and oxygenation. She was decannulated from ECLS shortly thereafter. IRB approval was waived due to the single case report nature. Consent was obtained for use of images and case data. Discussion Inflammatory modulation has been theorized to be beneficial in the management of organ failure secondary to coronavirus infection. A cytokine release syndrome (CRS) has been implicated in this disease\u2019s pathogenesis. Cytokine hemofiltration is one modality to mitigate harmful inflammation. Our patient demonstrated remarkable improvement with treatment and to our knowledge represents the first report of cytokine hemofiltration as management of COVID-19 respiratory failure in conjunction with VV-ECLS. This therapy warrants further evaluation as a treatment option.", "qid": 38, "docid": "izq70z47", "rank": 34, "score": 8.339799880981445}, {"content": "Title: Targeting the NLRP3 Inflammasome in Severe COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within the family Coronaviridae. It is an enveloped single-stranded positive-sense RNA virus. Since December of 2019, a global expansion of the infection has occurred with widespread dissemination of coronavirus disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe disease with complications occurs in 15% of cases. Respiratory failure occurs in severe disease that can be accompanied by a systemic inflammatory reaction characterized by inflammatory cytokine release. In severe cases, fatality is caused by the rapid development of severe lung injury characteristic of acute respiratory distress syndrome (ARDS). Although ARDS is a complication of SARS-CoV-2 infection, it is not viral replication or infection that causes tissue injury; rather, it is the result of dysregulated hyperinflammation in response to viral infection. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1\u03b2. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.", "qid": 38, "docid": "ehcqey3f", "rank": 35, "score": 8.309599876403809}, {"content": "Title: Pulmonary Angiotensin-Converting Enzyme 2 (ACE2) and Inflammatory Lung Disease. Content: In response to infectious and, in some instances, noninfectious insults, the affected tissues/cells of the host undergo inflammation. However, uncontrolled inflammation could be detrimental to the host, resulting in inflammatory disease, such as inflammatory lung disease. Although the etiology of the disease is well defined, the underling pathogenesis is still incompletely understood. The renin-angiotensin system (RAS), one of the primary cardiovascular regulatory systems, has been proposed to be involved in the pathogenesis of inflammatory lung disease. In particular, the RAS has been implicated as advances in the understanding of the multifunctionality of individual components of the system have been made, and by the fact that the RAS acts not only systemically, but also locally in a variety of tissues, including the lung. Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease. Nevertheless, the mechanism through which ACE2 plays a role in inflammatory lung disease has not been clearly identified. In an attempt to summarize current literature findings and progress made in uncovering the role of ACE2 in inflammatory lung disease, this review will focus on recent studies examining pulmonary ACE2 biology, its roles in inflammatory lung disease pathogenesis and possible underlying mechanisms. Finally, we will discuss pulmonary ACE2 as a potential therapeutic target for inflammatory lung disease.", "qid": 38, "docid": "jcezc9ue", "rank": 36, "score": 8.297599792480469}, {"content": "Title: The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics Content: Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (\u03b2), IL-8, and tumor necrosis factor-alpha (TNF-\u03b1), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.", "qid": 38, "docid": "8leknnvc", "rank": 37, "score": 8.284700393676758}, {"content": "Title: SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men's health and fertility.", "qid": 38, "docid": "tpoi31e7", "rank": 38, "score": 8.263299942016602}, {"content": "Title: SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men\u2019s health and fertility.", "qid": 38, "docid": "uju5m2zz", "rank": 39, "score": 8.263298988342285}, {"content": "Title: Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation Content: Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens. Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections. Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization. Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD. The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed. As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus. Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy. Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.", "qid": 38, "docid": "a577evo0", "rank": 40, "score": 8.225600242614746}, {"content": "Title: Covid-19: A systemic disease treated with a wide-ranging approach: A case report. Content: At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hospital, his breathing was normal. The nasopharyngeal swab specimen turned out positive. High-resolution computed tomography (HRCT) showed mild interstitial pneumonia. The patient was admitted to our department and treated with hydroxychloroquine, ritonavir, darunavir, azithromycin and enoxaparin. On day seven of the disease, the patient's respiratory condition got worse as he was developing acute respiratory distress syndrome (ARDS). He was given tocilizumab and corticosteroids and was immediately treated with non-invasive mechanical ventilation (NIMV). His condition improved, and in the ensuing days, the treatment gradually switched to a high-flow nasal cannula (HFNC); after 18 days, the patient's clinical condition was good.The successful results we have been able to obtain are closely associated with avoidance of invasive ventilation that may lead to intensive care unit (ICU)-related superinfections. In our opinion, it is fundamental to understand that COVID-19 is a systemic disease that is a consequence of an overwhelming inflammatory response, which can cause severe medical conditions, even in young patients.", "qid": 38, "docid": "shsnrhop", "rank": 41, "score": 8.209500312805176}, {"content": "Title: Covid-19: A systemic disease treated with a wide-ranging approach: A case report Content: At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hospital, his breathing was normal. The nasopharyngeal swab specimen turned out positive. High-resolution computed tomography (HRCT) showed mild interstitial pneumonia. The patient was admitted to our department and treated with hydroxychloroquine, ritonavir, darunavir, azithromycin and enoxaparin. On day seven of the disease, the patient's respiratory condition got worse as he was developing acute respiratory distress syndrome (ARDS). He was given tocilizumab and corticosteroids and was immediately treated with non-invasive mechanical ventilation (NIMV). His condition improved, and in the ensuing days, the treatment gradually switched to a high-flow nasal cannula (HFNC); after 18 days, the patient's clinical condition was good.The successful results we have been able to obtain are closely associated with avoidance of invasive ventilation that may lead to intensive care unit (ICU)-related superinfections. In our opinion, it is fundamental to understand that COVID-19 is a systemic disease that is a consequence of an overwhelming inflammatory response, which can cause severe medical conditions, even in young patients.", "qid": 38, "docid": "yolut5q9", "rank": 42, "score": 8.20949935913086}, {"content": "Title: Immuno-pathogenesis of nCOVID-19 and a possible host-directed therapy including anti-inflammatory and anti-viral prostaglandin (PG J(2)) for effective treatment and reduce the death toll Content: Coronaviruses including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also known as 2019-nCoV especially in China) replicate and divide in host cell. During this they are partly hidden from the innate immune responses although inflammatory consequences of viral replication still occur. We propose that anti-inflammatory antiviral prostaglandins may not only restrict viral replication but can also prevent inflammatory responses in the lungs and other vital organs that are known to be part of the immuno-pathogenesis of coronavirus disease-19 (COVID-19). The combination of anti-inflammatory antiviral prostaglandins with interferons may lead to the clearance of viruses inside the growth-restricted infected cells. However, further experimental studies and clinical trials should be conducted to evaluate the safety and efficacy of these possible therapies.", "qid": 38, "docid": "1hebq65a", "rank": 43, "score": 8.152299880981445}, {"content": "Title: New spectrum of COVID-19 manifestations in children: Kawasaki-like syndrome and hyperinflammatory response Content: Since late April 2020, data regarding Kawasaki-like syndrome and hyperinflammatory response in children associated with COVID-19 has rapidly emerged. Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is rare and early recognition is crucial though no standardized treatment guideline have been established. Worldwide collaboration will be important as more cases are recognized going forward.", "qid": 38, "docid": "5oijah15", "rank": 44, "score": 8.145600318908691}, {"content": "Title: New spectrum of COVID-19 manifestations in children: Kawasaki-like syndrome and hyperinflammatory response. Content: Since late April 2020, data regarding Kawasaki-like syndrome and hyperinflammatory response in children associated with COVID-19 has rapidly emerged. Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is rare and early recognition is crucial though no standardized treatment guideline have been established. Worldwide collaboration will be important as more cases are recognized going forward.", "qid": 38, "docid": "zdh1kvdj", "rank": 45, "score": 8.145599365234375}, {"content": "Title: Pathophysiology of viral-induced exacerbations of COPD Content: Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation.", "qid": 38, "docid": "hioh2s35", "rank": 46, "score": 8.138899803161621}, {"content": "Title: A close-up on COVID-19 and cardiovascular diseases Content: AIMS: To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. DATA SYNTHESIS: COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia, stress response, and so on; all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. CONCLUSION: In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, and maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis.", "qid": 38, "docid": "9xci72v0", "rank": 47, "score": 8.13860034942627}, {"content": "Title: COVID-19: pathogenesis, genetic polymorphism, clinical features and laboratory findings Content: COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (acute respiratory distress syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine these verity and prognosis of the disease, along with the condition and exposure of the affected systems during thecourse of COVID-19.", "qid": 38, "docid": "6hzlbpxg", "rank": 48, "score": 8.108799934387207}, {"content": "Title: COVID-19: Pathogenesis, Genetic Polymorphism, Clinical Features and Laboratory Findings. Content: COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE-2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (Acute Respiratory Distress Syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine the severity and prognosis of the disease, along with the condition and exposure of the affected systems during the course of COVID-19.", "qid": 38, "docid": "ot5v8n0c", "rank": 49, "score": 8.10879898071289}, {"content": "Title: Operation of mitochondrial machinery in viral infection-induced immune responses Content: Abstract Mitochondria have been recognized as ancient bacteria that contain evolutionary endosymbionts. Metabolic pathways and inflammatory signals interact within mitochondria in response to different stresses, such as viral infections. In this commentary, we address several interesting questions, including (1) how do mitochondrial machineries participate in immune responses; (2) how do mitochondria mediate antiviral immunity; (3) what mechanisms involved in mitochondrial machinery, including the downregulation of mitochondrial DNA (mtDNA), disturbances of mitochondrial dynamics, and the induction of mitophagy and regulation of apoptosis, have been adopted by viruses to evade antiviral immunity; (4) what mechanisms involve the regulation of mitochondrial machineries in antiviral therapeutics; and (5) what are the potential challenges and perspectives in developing mitochondria-targeting antiviral treatments? This commentary provides a comprehensive review of the roles and mechanisms of mitochondrial machineries in immunity, viral infections and related antiviral therapeutics.", "qid": 38, "docid": "zb98grls", "rank": 50, "score": 8.090999603271484}, {"content": "Title: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response Content: The most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is known about the initial responses of human lung alveoli to SARS-CoV-2 infection due in part to inability to access these cells from patients, particularly at early stages of disease. Here we present an in vitro human model that simulates the initial apical infection of the distal lung epithelium with SARS-CoV-2, using AT2s that have been adapted to air-liquid interface culture after their derivation from induced pluripotent stem cells (iAT2s). We find that SARS-CoV-2 induces a rapid global transcriptomic change in infected iAT2s characterized by a shift to an inflammatory phenotype predominated by the secretion of cytokines encoded by NF-kB target genes, delayed epithelial interferon responses, and rapid loss of the mature lung alveolar epithelial program. Over time, infected iAT2s exhibit cellular toxicity that can result in the death of these key alveolar facultative progenitors, as is observed in vivo in COVID-19 lung autopsies. Importantly, drug testing using iAT2s confirmed the efficacy of TMPRSS2 protease inhibition, validating putative mechanisms used for viral entry in human alveolar cells. Our model system reveals the cell-intrinsic responses of a key lung target cell to infection, providing a platform for further drug development and facilitating a deeper understanding of COVID-19 pathogenesis.", "qid": 38, "docid": "ulb3vy01", "rank": 51, "score": 8.088700294494629}, {"content": "Title: Identification and Analysis of Shared Risk Factors in Sepsis and High Mortality Risk COVID-19 Patients Content: BACKGROUND Coronavirus disease 2019 (COVID-19) is a novel coronavirus strain disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is highly transmissible and severe disease including viral sepsis has been reported in up to 16% of hospitalized cases. The admission characteristics associated with increased odds of hospital mortality among confirmed cases of COVID-19 include severe hypoxia, low platelet count, elevated bilirubin, hypoalbuminemia and reduced glomerular filtration rate. These symptoms correlate highly with severe sepsis cases. The diseases also share similar co-morbidity risks including dementia, type 2 diabetes mellitus, coronary heart disease, hypertension and chronic renal failure. Sepsis has been observed in up to 59% of hospitalized COVID-19 patients. It is highly desirable to identify risk factors and novel therapy/drug repurposing avenues for late-stage severe COVID-19 patients. This would enable better protection of at-risk populations and clinical stratification of COVID-19 patients according to their risk for developing life threatening disease. METHODS As there is currently insufficient data available for confirmed COVID-19 patients correlating their genomic profile, disease severity and outcome, co-morbidities and treatments as well as epidemiological risk factors (such as ethnicity, blood group, smoking, BMI etc.), a direct study of the impact of host genomics on disease severity and outcomes is not yet possible. We therefore ran a study on the UK Biobank sepsis cohort as a surrogate to identify sepsis associated signatures and genes, and correlated these with COVID-19 patients. Sepsis is itself a life-threatening inflammatory health condition with a mortality rate of approximately 20%. Like the initial studies for COVID-19 patients, standard genome wide association studies (GWAS) have previously failed to identify more than a handful of genetic variants that predispose individuals to developing sepsis. RESULTS We used a combinatorial association approach to analyze a sepsis population derived from UK Biobank. We identified 70 sepsis risk-associated genes, which provide insights into the disease mechanisms underlying sepsis pathogenesis. Many of these targets can be grouped by common mechanisms of action such as endothelial cell dysfunction, PI3K/mTOR pathway signaling, immune response regulation, aberrant GABA and neurogenic signaling. CONCLUSION This study has identified 70 sepsis related genes, many of them for the first time, that can reasonably be considered to be potentially relevant to severe COVID-19 patients. We have further identified 59 drug repurposing candidates for 13 of these targets that can be used for the development of novel therapeutic strategies to increase the survival rate of patients who develop sepsis and potentially severe COVID-19.", "qid": 38, "docid": "b8ce35l4", "rank": 52, "score": 8.087800025939941}, {"content": "Title: Natural killer cell activation related to clinical outcome of COVID-19 Content: Understanding innate immune responses in COVID-19 is important for deciphering mechanisms of host responses and interpreting disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections, but might also contribute to immune pathology. Here, using 28-color flow cytometry, we describe a state of strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients, a pattern mirrored in scRNA-seq signatures of lung NK cells. Unsupervised high-dimensional analysis identified distinct immunophenotypes that were linked to disease severity. Hallmarks of these immunophenotypes were high expression of perforin, NKG2C, and Ksp37, reflecting a high presence of adaptive NK cell expansions in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed in course of COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This provides a detailed map of the NK cell activation-landscape in COVID-19 disease.", "qid": 38, "docid": "727e1m3f", "rank": 53, "score": 8.081600189208984}, {"content": "Title: No indications for overt innate immune suppression in critically ill COVID-19 patients Content: At the end of March 2020, there were in excess of 800.000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide. Several reports suggest that, in severe cases, COVID-19 may cause a hyperinflammatory 'cytokine storm'. However, unlike SARS-CoV infection, high levels of anti-inflammatory mediators have also been reported in COVID-19 patients. One study reported that 16% of COVID-19 patients who died developed secondary infection, which might indicate an immune-suppressed state. We explored kinetics of mHLA-DR expression, the most widely used marker of innate immune suppression in critically ill patients, in COVID-19 patients admitted to the ICU. Twenty-four confirmed COVID-19 patients were included, of which 75% was male and 79% had comorbidities. All patients were mechanically ventilated and exhibited large high levels of inflammatory parameters such as CRP and PCT. mHLA-DR expression levels were mostly within the normal range of 15000 - 45000 mAb/cell and showed no change over time. COVID-19 patients displayed notably higher mHLA-DR expression levels compared with bacterial septic shock patients. None of the COVID-19 patients developed a secondary infection. In conclusion, despite a pronounced inflammatory response, mHLA-DR expression kinetics indicate no overt innate immune suppression in COVID-19 patients. These data signify that innate immune suppression as a negative feedback mechanism following PAMP-induced inflammation appears not to be present in COVID-19.", "qid": 38, "docid": "3ngrtmb0", "rank": 54, "score": 8.041600227355957}, {"content": "Title: Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway Content: Abstract SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients. Graphical Abstract", "qid": 38, "docid": "9gdi5447", "rank": 55, "score": 8.02299976348877}, {"content": "Title: Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy Content: In December 2019, Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, occurred in China and has currently led to a global pandemic. In addition to respiratory involvement, COVID-19 was also associated with significant multiple organ dysfunction syndrome (MODS). Cardiovascular impairment has been observed and is now drawing growing attention. Cardiovascular protective strategies are urgent and of great significance to the overall prognosis of COVID-19 patients. Direct viral infection, cytokine storm, and aggravation of existing cardiovascular diseases were recognized as possible mechanisms of cardiovascular impairment in COVID-19. Hyperactivated inflammation plays an important role in all three mechanisms and is considered to be fundamental in the development of cardiovascular impairment and MODS in COVID-19. Therefore, in addition to conventional cardiovascular treatment, anti-inflammatory therapy is a reasonable strategy for severe cases to further enhance cardiovascular protection and potentially mitigate MODS. We reviewed the inflammatory features and current promising treatments of COVID-19 as well as cardiovascular anti-inflammatory therapies that have been verified in previous clinical trials with positive outcomes. We believe that targeting the central pathway (IL-1\u03b2, TNF-\u03b1, IL-6), balancing the Th1 and Th2 response, and administering long-term anti-inflammatory therapy might be promising prospects to reduce cardiovascular impairment and even MODS during the acute and recovery phases of COVID-19. The cardiovascular anti-inflammatory therapies might be of great application value to the management of COVID-19 patients and we further propose an algorithm for the selection of anti-inflammatory therapy for COVID-19 patients with or at high risk of cardiovascular impairment. We recommend to take the experiences in cardiovascular anti-inflammatory therapy as references in the management of COVID-19 and conduct related clinical trials, while the clinical translation of novel treatments from preclinical studies or in vitro drug screening should proceed with caution due to unguaranteed efficacy and safety profiles.", "qid": 38, "docid": "ca82o6do", "rank": 56, "score": 7.989699840545654}, {"content": "Title: An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes? Content: Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.", "qid": 38, "docid": "sgw0iaz4", "rank": 57, "score": 7.973299980163574}, {"content": "Title: Hepatic involvement in COVID-19 patients: pathology, pathogenesis and clinical implications [Review]. Content: During the clinical course of COVID-19, it has been observed that hepatic injury occurs in a significant proportion of patients, particularly in those with severe or critical illness. Mild increase in sinusoidal lymphocytic infiltration and multifocal hepatic necrosis are the main pathologic changes. Direct viral induced cellular injuries and potential hepatotoxicity from therapeutic drugs are two likely underlying mechanisms. In addition, preexisting chronic liver disease exacerbated during COVID-19, and COVID-19-related hyper-inflammatory reactions may contribute to liver injury as well. Further studies of additional autopsy cases will help clarifying these possibilities. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "dskymg3e", "rank": 58, "score": 7.967599868774414}, {"content": "Title: Role of Regulatory T Cells in Pathogenesis and Biological Therapy of Multiple Sclerosis Content: Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. It is caused by an autoimmune response to self-antigens in a genetically susceptible individual induced by unknown environmental factors. Principal cells of the immune system that drive the immunopathological processes are T cells, especially of T(H)1 and T(H)17 subsets. However, in recent years, it was disclosed that regulatory T cells took part in, too. Subsequently, there was endeavour to develop ways how to re-establish their physiological functions. In this review, we describe known mechanisms of action, efficacy, and side-effects of contemporary and emerging MS immunotherapeutical agents on Treg cells and other cells of the immune system involved in the immunopathogenesis of the disease. Furthermore, we discuss how laboratory immunology can offer physicians its help in the diagnosis process and decisions what kind of biological therapy should be used.", "qid": 38, "docid": "gkbeqifb", "rank": 59, "score": 7.938799858093262}, {"content": "Title: COVID-19. Immunothrombosis and the gastrointestinal tract Content: M\u00f6nkem\u00fcller et al. brilliantly describe the pathogenesis of SARS-CoV-2 (COVID-19) in the gastrointestinal tract. Their findings highlight the local and systemic inflammatory response generated by the coronavirus. After having the opportunity to observe three cases of severe colonic ischemia and elevation of D-dimer levels in patients with COVID-19 and severe acute respiratory distress syndrome (SARS) due to SARS-CoV-2, we would like to highlight the thromboembolic complications in COVID-19, which are related to those reported by M\u00f6nkem\u00fcller and which have been mentioned by other authors.", "qid": 38, "docid": "kyq9mouj", "rank": 60, "score": 7.926000118255615}, {"content": "Title: COVID-19. Immunothrombosis and the gastrointestinal tract. Content: M\u00f6nkem\u00fcller et al. brilliantly describe the pathogenesis of SARS-CoV-2 (COVID-19) in the gastrointestinal tract. Their findings highlight the local and systemic inflammatory response generated by the coronavirus. After having the opportunity to observe three cases of severe colonic ischemia and elevation of D-dimer levels in patients with COVID-19 and severe acute respiratory distress syndrome (SARS) due to SARS-CoV-2, we would like to highlight the thromboembolic complications in COVID-19, which are related to those reported by M\u00f6nkem\u00fcller and which have been mentioned by other authors.", "qid": 38, "docid": "l3ju3w3r", "rank": 61, "score": 7.925999164581299}, {"content": "Title: Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement Content: INTRODUCTION: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options. CASES: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). DISCUSSION: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium. CONCLUSIONS: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.", "qid": 38, "docid": "hhzcxu92", "rank": 62, "score": 7.887899875640869}, {"content": "Title: The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge Content: The filoviruses, ebolavirus (EBOV) and marburgvirus (MARV), are highly lethal zoonotic agents of concern as emerging pathogens and potential bioweapons. Antigen-presenting cells (APCs), particularly macrophages and dendritic cells, are targets of filovirus infection in vivo. Infection of these cell types has been proposed to contribute to the inflammation, activation of coagulation cascades and ineffective immune responses characteristic of filovirus hemorrhagic fever. However, many aspects of filovirus-APC interactions remain to be clarified. Among the unanswered questions: What determines the ability of filoviruses to replicate in different APC subsets? What are the cellular signaling pathways that sense infection and lead to production of copious quantities of cytokines, chemokines and tissue factor? What are the mechanisms by which innate antiviral responses are disabled by these viruses, and how may these mechanisms contribute to inadequate adaptive immunity? A better understanding of these issues will clarify the pathogenesis of filoviral hemorrhagic fever and provide new avenues for development of therapeutics.", "qid": 38, "docid": "ymd5zt37", "rank": 63, "score": 7.850100040435791}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 38, "docid": "afx2wv9d", "rank": 64, "score": 7.843400001525879}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin. Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 38, "docid": "rx1k9hu5", "rank": 65, "score": 7.8433990478515625}, {"content": "Title: Pathogenesis of virus-induced immune-mediated demyelination Content: Theiler's murine encephalomyelitis virus-induced demyelinating disease has been extensively studied as an attractive infectiousmodel for human multiple sclerosis. Virus-specific inflammatory Th1 cell responses followed by autoimmune responses to myelin antigens play a crucial role in the pathogenic processes leading to demyelination. Antibody and cytotoxic T cells (CTL) responses to virus appears to be primarily protective from demyelinating disease. Although the role of Th1 and CTL responses in the induction of demyelinating disease is controversial, assessment of cytokine sproduced locally in the central nervous system (CNS) during the course of disease and the effects of altered inflammatory cytokine levels strongly support the importance of Th1 responses in this virus-induced demyelinating disease. Induction of various chemokines and cytokines in different glial and antigen presenting cells upon viral infection appears to be an important initiation mechanism for inflammatory Th1 responses in the CNS. Coupled with the initial inflammatory responses, viral persistence in the CNS may be acritical factor for sustaining inflammatory responses and consequent immune-mediated demyelinating disease.", "qid": 38, "docid": "3bi75xn8", "rank": 66, "score": 7.838799953460693}, {"content": "Title: The case of complement activation in COVID-19 multiorgan impact Content: The novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation, and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review, we discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multiorgan damage.", "qid": 38, "docid": "0mien60n", "rank": 67, "score": 7.826099872589111}, {"content": "Title: The case of Complement activation in COVID-19 multiorgan impact Content: The novel coronavirus disease COVID-19 originates in the lungs, but may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review we will discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multi-organ damage.", "qid": 38, "docid": "ynze6yaz", "rank": 68, "score": 7.826098918914795}, {"content": "Title: Pulmonary Toxicity and Inflammatory Response of E-Cigarette Vape Cartridges Containing Medium-Chain Triglycerides Oil and Vitamin E Acetate: Implications in the Pathogenesis of EVALI. Content: Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT), may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig vape cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of e-cig vape cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig vape cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined SARS-CoV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig vape cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated proinflammatory markers in the pathogenesis of EVALI.", "qid": 38, "docid": "vpcaa8u0", "rank": 69, "score": 7.81850004196167}, {"content": "Title: Attenuated interferon and pro-inflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation Content: Clinical manifestations of COVID-19 vary from asymptomatic virus shedding, non-specific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of SARS and MERS. However, the interplay between SARS-CoV-2 and these cell types remains unknown. Herein, we investigated the infection and host response of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. We demonstrated that moDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types. Additionally, SARS-CoV-2 triggered significant pro-inflammatory cytokine/chemokine expression in MDMs but not in moDCs. Further investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings on pathogenesis may explain the mild and insidious course of COVID-19 till late deterioration.", "qid": 38, "docid": "fwtohhe2", "rank": 70, "score": 7.799699783325195}, {"content": "Title: Immunological and inflammatory profiles in mild and severe cases of COVID-19 Content: COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.", "qid": 38, "docid": "j6jb4j3b", "rank": 71, "score": 7.798900127410889}, {"content": "Title: Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment Content: COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-&#945; agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "qid": 38, "docid": "57qod8v1", "rank": 72, "score": 7.795199871063232}, {"content": "Title: Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment Content: COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-\u03b1 agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "qid": 38, "docid": "r3a3xr8b", "rank": 73, "score": 7.795198917388916}, {"content": "Title: Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach Content: The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.", "qid": 38, "docid": "1evug4fr", "rank": 74, "score": 7.782299995422363}, {"content": "Title: Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach Content: The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present review looks to highlight the differences in genomic, proteomic, pathogenesis, and therapeutic strategies of SARS-CoV-2. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV-1 and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins was performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.", "qid": 38, "docid": "dfydh7sf", "rank": 75, "score": 7.782299041748047}, {"content": "Title: Coronavirus Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages Content: Coronaviruses encode multiple interferon antagonists that modulate the host response to virus replication. Here, we evaluated pathogenesis and host transcription in response to infection with murine coronaviruses encoding independent mutations in two different viral antagonists: the deubiquitinase (DUB) within nonstructural protein 3 and the endoribonuclease (EndoU) within nonstructural protein 15. The virus with reduced ability to deubiquitinate proteins, herein termed the DUBmut virus, was engineered via X-ray structure-guided mutagenesis and activates an earlier interferon response than the wild type virus. However, the replication kinetics of DUBmut in cultured cells are similar to wild type virus and pathogenesis in mice is also similar to what was observed during infection with wild type virus. On the other hand, we previously reported that an EndoUmut virus containing an inactivated endoribonuclease activity elicited rapid and robust activation of type I interferon, which limited virus replication and pathogenesis. Here, using a transcriptomics approach, we compared the scope and kinetics of the host response to the wild type, DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response, predominantly involving type I interferons and a subset of interferon-responsive genes, within 12 hours after infection. In contrast, the wild type and DUBmut viruses stimulate upregulation of over 2,800 genes, including activation of unfolded protein response (UPR) pathways and a proinflammatory profile associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivation of a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages and the disease process. Author Summary Macrophages are an important cell type during coronavirus infections because they \u201cnotice\u201d the infection and respond by activating type I interferons, which then act to establish antiviral defenses and limit virus replication. In turn, coronaviruses encode proteins that mitigate the cell\u2019s ability to detect virus replication or amplify the interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses: one with a reduced deubiquitinating activity (DUBmut), and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-stimulated genes. These results indicate that coronaviruses utilize EndoU activity for preventing early activation of interferon in macrophages, thereby allowing for viral replication. In contrast, DUBmut elicited a transient interferon response and ultimately activated over 2,800 genes, including many well-known players in pro-inflammatory pathways and the unfolded protein response. These DUBmut-induced pathways are associated with development and progression of significant disease, similar to what is observed during wild type virus infection. This study demonstrates the distinct consequences of mutating different viral interferon antagonists and reveals that intact coronaviral EndoU activity substantially contributes to the ability of coronaviruses to replicate in macrophages.", "qid": 38, "docid": "l3qp0n9f", "rank": 76, "score": 7.759200096130371}, {"content": "Title: Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19. Content: Eosinophils were discovered more than 140 years ago. This polymorphonuclear leukocyte has a very active metabolism, containing numerous intracellular secretory granules that allow it exerts multiple functions in both health and disease status. Classically, eosinophils have been considered as important immune cells in the pathogenesis of inflammatory processes such as parasitic helminth infections and allergic or pulmonary diseases like asthma, being always associated to a type 2 immune response; furthermore, in the last years, it has been linked to immune response conferring host protection against fungi, bacteria, and viruses, recognizing them through several molecules such as toll-like receptors (TLRs) or retinoic acid-inducible gene 1 (RIG-1)-like receptor (RLR). The immune protection is exerted through multiple mechanisms and properties of these cells. They contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines and other molecules that contribute to their functions. In addition to their competence as effectors cells, its capabilities like antigen-presenting cell allow them to act in multiple situations promoting diverse aspects of the immune response. This review summarizes diverse aspects of eosinophil biology and mainly, it goes over the mechanisms and roles carried out by eosinophils in host defence against virus infections and vaccines response, focusing the attention in respiratory viruses like the new coronavirus, SARS-CoV-2.", "qid": 38, "docid": "pmxc9u82", "rank": 77, "score": 7.739099979400635}, {"content": "Title: Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19 Content: Eosinophils were discovered more than 140 years ago. This polymorphonuclear leukocyte has a very active metabolism, containing numerous intracellular secretory granules that allow it exerts multiple functions in both health and disease status. Classically, eosinophils have been considered as important immune cells in the pathogenesis of inflammatory processes such as parasitic helminth infections and allergic or pulmonary diseases like asthma, being always associated to a type 2 immune response; furthermore, in the last years, it has been linked to immune response conferring host protection against fungi, bacteria, and viruses, recognizing them through several molecules such as toll-like receptors (TLRs) or retinoic acid-inducible gene 1 (RIG-1)-like receptor (RLR). The immune protection is exerted through multiple mechanisms and properties of these cells. They contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines and other molecules that contribute to their functions. In addition to their competence as effectors cells, its capabilities like antigen-presenting cell allow them to act in multiple situations promoting diverse aspects of the immune response. This review summarizes diverse aspects of eosinophil biology and mainly, it goes over the mechanisms and roles carried out by eosinophils in host defence against virus infections and vaccines response, focusing the attention in respiratory viruses like the new coronavirus, SARS-CoV-2.", "qid": 38, "docid": "pv6sqk4j", "rank": 78, "score": 7.739099025726318}, {"content": "Title: Immunopathology of highly virulent pathogens: insights from Ebola virus Content: Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus\u2013infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus.", "qid": 38, "docid": "ekmuz4ug", "rank": 79, "score": 7.734799861907959}, {"content": "Title: Elevated serum levels of decoy receptor 3 are associated with disease severity in patients with hemorrhagic fever with renal syndrome Content: Hemorrhagic fever with renal syndrome (HFRS) is an acute viral infectious disease characterized by fever, hemorrhage and renal failure. HFRS has become a serious public health problem in China. Unfortunately, the pathogenesis of HFRS has not been completely clarified. The aim of this study is to investigate the changes of decoy receptor 3 (DcR3) and to further explore its potential roles in HFRS. The levels of serum DcR3 were measured by sandwich ELISA. We found serum DcR3 levels increased significantly, which reached peak value during the oliguric phase and in the critical group. Moreover, serum DcR3 levels were closely related to the levels of pro-inflammatory cytokines tumor necrosis factor-\u03b1 (TNF-\u03b1) and parameters reflecting kidney injury including BUN, creatinine (Cr) and proteinuria. This study indicates that high levels of serum DcR3 have associations with the disease stages, severity and degree of kidney damage. Meanwhile, our results suggest that DcR3 may play a dual role in HFRS pathogenesis. First, DcR3 is involved in the inflammatory cascade response resulting in capillary permeability and kidney injury in the early stage. Secondly, HTNV infection induced DcR3 expression at the convalescent phase may act as a feed-back mechanism in anti-inflammatory response. Thus, a study of DcR3 is essential for a better understanding of HFRS pathogenesis.", "qid": 38, "docid": "d35uzf45", "rank": 80, "score": 7.70550012588501}, {"content": "Title: Expression of inflammation-related genes in the lung of BALB/c mice response to H7N9 influenza A virus with different pathogenicity Content: H7N9 influenza A virus (IAV)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. Host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced \u201ccytokine storm\u201d also leads to pathological lesions. However, what inflammation-related response of the host for H7N9 influenza A virus infection to survival from injures of exuberant cytokine release is still obscure. In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1\u03b2, TNF-\u03b1, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 residue 627 difference were investigated, as well as the histopathological injury of the lung. Results showed that significantly higher expression level of NLRP3, RIP3, IL-1\u03b2 and TNF-\u03b1 in H7N9-infected groups compared with the control would play a key role in driving lung pathological lesion. While the expression level of Slit2 and Robo4 in H7N9 rV(K627E) group had significantly increased trend than V(K627) which might be the main factor to inhibit the interstitial pneumonia and infiltration. Also, H7N9 induced the histopathological changes in the lung of infected mice, and RIP3, NLRP3, IL-1\u03b2, TNF-\u03b1, Slit2 and Robo4 showed cell-specific distribution in the lung. The results will provide basic data for further research on the mechanism of inflammatory response and understanding of the role of site 627 in PB2 in H7N9 IAVs infection. In addition, enhancing the resilience of the host vascular system to the inflammatory response by regulation of Slit2\u2013Robo4 signaling pathway might provide a novel strategy for H7N9 IAVs infection.", "qid": 38, "docid": "pyrfgggz", "rank": 81, "score": 7.689799785614014}, {"content": "Title: Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients Content: Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1, 2 Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported at December 2019 in the city Wuhan, Hubei province, China3, 4, 5, which was also named as pneumonia-associated respiratory syndrome (PARS)6 and can cause coronavirus disease 2019 (COVID-19) to seriously endanger human health Up to 24th of February 2020, at least 77779 cases have been reported with 2666 fatal cases according to the report from China CDC However, the immune mechanism that potential orchestrated acute mortality from COVID-19 patients is still unknown Here we show that after the SARS-CoV-2 infection, CD4+ T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerate the inflammation Given that large amount of inflammatory cells infiltrations have been observed in lungs from severe COVID-19 patients7, 8, these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology Thus, we suggest that monoclonal antibodies targeting GM-CSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients", "qid": 38, "docid": "iqx0rxun", "rank": 82, "score": 7.689300060272217}, {"content": "Title: Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients Content: Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients\u2019 lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.", "qid": 38, "docid": "0daf0i75", "rank": 83, "score": 7.68720006942749}, {"content": "Title: Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients Content: Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.", "qid": 38, "docid": "5nx2l9kf", "rank": 84, "score": 7.687199115753174}, {"content": "Title: Inflammatory responses relate to distinct bronchoalveolar lavage lipidome in community-acquired pneumonia patients: a pilot study Content: BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the \u201clipidomic phenotype\u201d can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. METHODS: Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS). Principal component analysis (PCA) was applied to identify possible sources of variations among samples. Partitioning clustering analysis (k-means) was employed to evaluate the existence of distinct lipidomic clusters. RESULTS: PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases. Lactosylceramides were the most prominently elevated lipid constituent in CAP. Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p < 0.05). In addition, SM (d34:1) was negatively related to macrophage (adjusted r = \u2212 0.462, p < 0.0001) and PE (18:1p/20:4) was positively correlated with polymorphonuclear neutrophil (PMN) percentages of BALF (adjusted r = 0.541, p < 0.0001). The 30-day mortality did not differ amongst three clusters (p < 0.05). CONCLUSIONS: Our data suggest that specific lower airway lipid composition is related to different intensities of host inflammatory responses, and may contribute to functionally relevant shifts in disease pathogenesis in CAP individuals. These findings argue for the need to tailor therapy based on specific lipid profiles and related inflammatory status. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03093220). Registered on 28 March 2017 (retrospectively registered). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1028-8) contains supplementary material, which is available to authorized users.", "qid": 38, "docid": "bdcjw336", "rank": 85, "score": 7.685800075531006}, {"content": "Title: Harnessing resolving\u2010based therapeutics to treat pulmonary viral infections: What can the future offer to COVID\u201019? Content: Inflammation is generally believed to be a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Multiple mediators that drive the resolution of inflammation have been described. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro\u2010resolving molecules or strategies that promote their increase tend to decrease inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti\u2010inflammatory, pro\u2010resolving, anti\u2010thrombogenic and anti\u2010microbial effects of pro\u2010resolution mediators may be useful in the treatment of the late stages of disease in patients with COVID\u201019.", "qid": 38, "docid": "ntd3yve7", "rank": 86, "score": 7.660999774932861}, {"content": "Title: Harnessing inflammation resolving-based therapeutic agents to treat pulmonary viral infections: What can the future offer to COVID-19? Content: Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro-resolution molecules, or strategies that promote their increase, tend to suppress inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti-inflammatory, pro-resolving, anti-thrombogenic and anti-microbial effects of such endogenous mediators of resolution may be useful in the treatment of the late stages of the disease in patients with COVID-19.", "qid": 38, "docid": "z5z7db0b", "rank": 87, "score": 7.660998821258545}, {"content": "Title: Microglia Are Essential to Protective Antiviral Immunity: Lessons From Mouse Models of Viral Encephalitis Content: Viral encephalitis is a rare but clinically serious consequence of viral invasion of the brain and insight into its pathogenesis is urgently needed. Important research questions concern the involvement of the host innate immune response in pathogenesis, key to which is the role played by microglia, resident macrophages of the brain parenchyma. Do microglia have a protective function, by coordinating the innate immune response to viral infection, or do they drive pathogenic neuroinflammation? Here we synthesize recent data from mouse models of acute viral encephalitis, which reveal an unambiguously protective role for microglia. Depletion of microglia, via blockade of colony-stimulating factor 1 receptor (CSF1R) signaling, led to increased viral replication accompanied by more severe neurological disease and heightened mortality. Whilst the underlying mechanism(s) remain to be defined, microglial interactions with T cells and phagocytosis of infected neurones appear to play a role. Paradoxically, the production of inflammatory cytokines was increased in several instances following viral infection in microglia-depleted brains, suggesting that: (i) cells other than microglia mediate inflammatory responses and/or (ii) microglia may exert a regulatory function. Under certain circumstances the microglial antiviral response might contribute negatively to longer-term neurological sequelae, although fewer studies have focused on this aspect in encephalitis models. Understanding regulation of the microglial response, and how it contributes to disease is therefore a priority for future studies. Collectively, these findings demonstrate the central role of microglia in pathogenesis, suggesting the exciting possibility that defects of microglial function might contribute to encephalitis susceptibility and/or outcome in humans.", "qid": 38, "docid": "ti2fr0uh", "rank": 88, "score": 7.655200004577637}, {"content": "Title: COVID 19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Content: Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID\u201019) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID\u201019 with higher percentages, 25%\u201335% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by the exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID\u201019. A key role may be that of the renin\u2013angiotensin\u2010aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infects human cells binding to angiotensin\u2010converting\u2010enzyme 2 (ACE2), an enzyme responsible of the cleavage of angiotensin II into angiotensin 1\u20137, which has vasodilating and anti\u2010inflammatory effects. Virus\u2010mediated downregulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper\u2010inflammatory reaction of COVID\u201019. On the other hand, ACE2 may be upregulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 upregulation may increase the susceptibility to COVID\u201019 but may be also protective versus angiotensin II mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID\u201019 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "17hyh3n5", "rank": 89, "score": 7.653800010681152}, {"content": "Title: COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Content: Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.", "qid": 38, "docid": "5svfhlzh", "rank": 90, "score": 7.653799057006836}, {"content": "Title: Neuropilin-1 modulates interferon-\u03b3-stimulated signaling in brain microvascular endothelial cells. Content: Inflammatory response of blood-brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-\u03b3 (IFN\u03b3)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner. Moreover, endothelial-specific NRP1-knockout mice, VECadherin-Cre-ERT2/NRP1flox/flox mice, showed attenuated disease progression during experimental autoimmune encephalomyelitis, a mouse neuroinflammatory disease model. Detailed analysis utilizing histological staining, quantitative PCR, flow cytometry and magnetic resonance imaging demonstrated that deletion of endothelial NRP1 suppressed neuron demyelination, altered lymphocyte infiltration, preserved BBB function and decreased activation of the STAT1-CXCL10 pathway. Furthermore, increased expression of NRP1 was observed in endothelial cells of acute multiple sclerosis lesions. Our data identify a new molecular mechanism of brain microvascular endothelial inflammatory response through NRP1-IFN\u03b3 crosstalk that could be a potential target for intervention of endothelial cell dysfunction in neuroinflammatory diseases.", "qid": 38, "docid": "f7isruy0", "rank": 91, "score": 7.64709997177124}, {"content": "Title: Differential diagnosis and clinical management of a case of COVID-19 in a stage III lung cancer patient treated with radio-chemotherapy and durvalumab. Content: BACKGROUND: pneumonitis is common in NSCLC and can be a consequence of the disease itself, super-infection, or side effects of the treatment. Recently Covid-19 added to the list of possible causes, emerging as a concrete threat for already frail patients. CASE REPORT: a 75-years-old stage-III NSCLC patient underwent radical radio-chemotherapy followed by consolidation durvalumab at our Institution. After four cycles, immunotherapy was suspended due to symptomatic pneumonitis responsive to oral steroids. Nevertheless, he suddenly developed fever and severe dyspnea. Chest radiography described diffuse alveolar and interstitial infiltrates and RT-PCR confirmed the diagnosis of Covid-19. His clinical conditions worsened despite antiviral therapy and supplemental oxygen and the patient died three days after admission. DISCUSSION: this paper highlights the remarkable clinical and radiological similarity of pneumonitis causated by Covid-19 and immunotherapy, hampering differential diagnosis and corroborating the hypothesis that inflammatory molecules, and possibly PD-L1, play a central role in Covid-19 pathogenesis.", "qid": 38, "docid": "k9hut687", "rank": 92, "score": 7.640600204467773}, {"content": "Title: COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies Content: The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.", "qid": 38, "docid": "hmpmm9k8", "rank": 93, "score": 7.615099906921387}, {"content": "Title: Transcriptomic profiling of disease severity in patients with COVID-19 reveals role of blood clotting and vasculature related genes Content: COVID-19 caused by SARS-CoV-2 manifests as a range of symptoms. Understanding the molecular mechanisms responsible for immuno-pathogenesis of disease is important for treatment and management of COVID-19. We examined host transcriptomes in moderate and severe COVID-19 cases with a view to identifying pathways that affect its progression. RNA extracted from whole blood of COVID-19 cases was analysed by microarray analysis. Moderate and severe cases were compared with healthy controls and differentially regulated genes (DEGs) categorized into cellular pathways. DEGs in COVID-19 cases were mostly related to host immune activation and cytokine signaling, pathogen uptake, host defenses, blood and vasculature genes, and SARS-CoV-2- and other virus- affected pathways. The DEGs in these pathways were increased in severe compared with moderate cases. In a severe COVID-19 patient with an unfavourable outcome we observed dysregulation of genes in platelet homeostasis and cardiac conduction and fibrin clotting with disease progression.", "qid": 38, "docid": "yrelcfx9", "rank": 94, "score": 7.608099937438965}, {"content": "Title: Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis Content: Abstract Crimean Congo hemorrhagic fever virus (CCHFV) causes an acute disease with the potential of a fatal outcome. The virus is prevalent in about 30 countries. Clinical symptoms of infection commonly include fever, myalgia, and hemorrhages. Levels of liver enzymes are raised, and bleeding markers are often increased. A role of inflammatory cytokines in the pathogenesis has been suggested, and CCHFV employs a range of passive and active mechanisms to avoid induction of the antiviral type I interferons. Here, we review the most recent findings on the molecular pathogenesis and the interaction of CCHFV with the type I interferon and cytokine responses and discuss implications for pathogenesis.", "qid": 38, "docid": "zedd7ug4", "rank": 95, "score": 7.592100143432617}, {"content": "Title: Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy Content: The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.", "qid": 38, "docid": "040w9ba1", "rank": 96, "score": 7.5883002281188965}, {"content": "Title: COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Content: To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.", "qid": 38, "docid": "mg8uyeuh", "rank": 97, "score": 7.573999881744385}, {"content": "Title: COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis Content: To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.", "qid": 38, "docid": "zwsp463x", "rank": 98, "score": 7.573998928070068}, {"content": "Title: Contribution of Fc\u03b3 Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus Content: The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (Fc\u03b3Rs) expressed on the surface of immune cells. Furthermore, a role for Fc\u03b3Rs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that Fc\u03b3Rs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing Fc\u03b3Rs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and Fc\u03b3Rs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding Fc\u03b3Rs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.", "qid": 38, "docid": "yd2p1buu", "rank": 99, "score": 7.567999839782715}, {"content": "Title: Cancer Patients Have a Higher Risk Regarding COVID-19 - and Vice Versa? Content: The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19 However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection", "qid": 38, "docid": "udce22id", "rank": 100, "score": 7.565499782562256}]}
{"query": "What is the mechanism of cytokine storm syndrome on the COVID-19?", "hits": [{"content": "Title: [Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019] Content: Coronavirus disease 2019 (COVID-19) has seriously affected the safety of patients and social stability. Some COVID-19 patients in the later stage of disease may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanisms underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm with some progresses being achieved. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "zukc3lvq", "rank": 1, "score": 12.485899925231934}, {"content": "Title: [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies] Content: Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "3d04p4xp", "rank": 2, "score": 12.451299667358398}, {"content": "Title: [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]. Content: Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "urr5iuy2", "rank": 3, "score": 12.451298713684082}, {"content": "Title: Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review Content: COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic The disease continues to pose a major therapeutic challenge Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS) Cytokine release syndrome (or \"cytokine storm\") is likely to be a contributing factor to ARDS in many patients Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc) The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation Ultimately, the patient was downgraded from the ICU and discharged within days We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19 Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality-the cytokine storm This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19", "qid": 39, "docid": "jorwzkld", "rank": 4, "score": 12.278800010681152}, {"content": "Title: The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of \u201cinflame-aging\u201d Content: PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by \u201cinflamm-aging\u201d. It is highly likely that \u201cinflamm-aging\u201d is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of \u201cinflamm-aging\u201d, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.", "qid": 39, "docid": "7ak53hto", "rank": 5, "score": 12.003299713134766}, {"content": "Title: The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of \"inflame-aging\" Content: PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by \"inflamm-aging\". It is highly likely that \"inflamm-aging\" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of \"inflamm-aging\", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.", "qid": 39, "docid": "w6b1h1of", "rank": 6, "score": 12.00329875946045}, {"content": "Title: Tocilizumab: A Therapeutic Option for the Treatment of Cytokine Storm Syndrome in COVID-19 Content: Abstract Presently, we need more therapeutic molecules for this COVID-19 outbreak. The severity and mortality of the disease is associated with a high level of release of cytokine in the patients which is known as CRS (cytokine release syndrome) or cytokine storm syndrome. IL-6 is a type of pro-inflammatory cytokine which release in the severe COVID-19 patients. This cytokine initiates CRS the JAK-STAT pathway. Tocilizumab, a humanized monoclonal antibody, is designed to bind both mIL-6R (membrane bound receptor for IL-6) and sIL-6R (soluble receptor for IL-6) and inhibit the JAK-STAT signaling pathway. It finally stops the cytokine storm syndrome. However, we need to understand that how tocilizumab is bound with mIL-6R or sIL-6R. Similarly, we also need to understand more about the real molecular mechanism of activity of tocilizumab.", "qid": 39, "docid": "5c9f4m2f", "rank": 7, "score": 11.957099914550781}, {"content": "Title: Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia Content: Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that \u2053 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and \u201cDiagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)\u201d in China, so as to provide reference for the treatment of COVID-19.", "qid": 39, "docid": "nqprluto", "rank": 8, "score": 11.873499870300293}, {"content": "Title: Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment Content: COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-&#945; agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "qid": 39, "docid": "57qod8v1", "rank": 9, "score": 11.866800308227539}, {"content": "Title: Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment Content: COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-\u03b1 agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "qid": 39, "docid": "r3a3xr8b", "rank": 10, "score": 11.866799354553223}, {"content": "Title: Cytokine Storm Induced by SARS-CoV-2 Content: A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.", "qid": 39, "docid": "fozglfc8", "rank": 11, "score": 11.850000381469727}, {"content": "Title: Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia Content: Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that \u00e2\u0081\u0093 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and \"Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)\" in China, so as to provide reference for the treatment of COVID-19.", "qid": 39, "docid": "yaov2osz", "rank": 12, "score": 11.814200401306152}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \"cytokine storm\" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 39, "docid": "ete5n5pw", "rank": 13, "score": 11.721199989318848}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \u201ccytokine storm\u201d induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 39, "docid": "ne1qvf5g", "rank": 14, "score": 11.721199035644531}, {"content": "Title: The cytokine storm and COVID-19 Content: Coronavirus disease 2019 (COVID-19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of May 11, 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "hqzkzupi", "rank": 15, "score": 11.65369987487793}, {"content": "Title: The cytokine storm and COVID\u201019 Content: Coronavirus disease 2019 (COVID\u201019), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID\u201019, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), have been confirmed as of May 11, 2020. SARS\u2010CoV\u20102 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID\u201019 severity and is also a crucial cause of death from COVID\u201019. In the absence of antivirals and vaccines for COVID\u201019, there is an urgent need to understand the cytokine storm in COVID\u201019. Here, we have reviewed the current understanding of the features of SARS\u2010CoV\u20102 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID\u201019. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "rvrgcugn", "rank": 16, "score": 11.653698921203613}, {"content": "Title: Weather the Cytokine Storm: A Report of Successful Management of a Colon Cancer Survivor and a Critically Ill Patient with COVID-19 Content: Patients with novel corona virus infection (COVID-19) can develop acute respiratory failure secondary to acute respiratory distress syndrome. Cytokine storm is suggested as one of underlying mechanisms for the rapid clinical decline. Immunocompromised patients and cancer patients are at particular risk for poor outcomes due to COVID-19 infection. This case report describes the presentation and clinical course of a cancer survivor who became critically ill and required mechanical ventilation. The patient was treated with hydroxychloroquine, azithromycin, and ceftriaxone; however, he remained febrile, hypoxemic, continued to require full mechanical ventilator support and his chest X-ray showed increased bilateral infiltrates. The patient was treated with tocilizumab, after which he improved and was successfully extubated. This report illustrates a possible role of tocilizumab in management of cytokine storm in critically ill patients with COVID-19 infection.", "qid": 39, "docid": "a8jt6rth", "rank": 17, "score": 11.521100044250488}, {"content": "Title: Cytokine storm induced by SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.", "qid": 39, "docid": "bxfyse59", "rank": 18, "score": 11.458600044250488}, {"content": "Title: Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications Content: The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.", "qid": 39, "docid": "o9xh6bqz", "rank": 19, "score": 11.373100280761719}, {"content": "Title: Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 39, "docid": "1w7g6dkq", "rank": 20, "score": 11.352999687194824}, {"content": "Title: Immune response to SARS\u2010CoV\u20102 and mechanisms of immunopathological changes in COVID\u201019 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID\u201019) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to detoriating clinical conditions such as, cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute phase reactants and serum biochemistry in COVID\u201019. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals.In the majority of the patients, a one\u2010week, self\u2010limiting viral respiratory disease typically occurs, which ends with the development of neutralizing anti\u2010viral T cell and antibody immunity. The IgM, IgA and IgG type virus\u2010specific antibodies levels are important measurements to predict population immunity against this disease and whether cross\u2010reactivity with other coronaviruses is taking place.High viral\u2010load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID\u201019 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine\u2010secreting cells with innate and adaptive immune mechanisms both of with contribute to a poor prognosis. Elevated levels of acute phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome and novel approachs to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 39, "docid": "fczf3lzc", "rank": 21, "score": 11.352998733520508}, {"content": "Title: COVID-19 cytokine storm: The anger of inflammation Content: Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.", "qid": 39, "docid": "s82qv18v", "rank": 22, "score": 11.344099998474121}, {"content": "Title: Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts Content: Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL-6, IL-1\u00df, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-3, and IL-1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID-19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID-19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID-19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "qid": 39, "docid": "nmdko4nl", "rank": 23, "score": 11.31350040435791}, {"content": "Title: Cytokine storm and leukocyte changes in mild versus severe SARS\u2010CoV\u20102 infection: Review of 3939 COVID\u201019 patients in China and emerging pathogenesis and therapy concepts Content: Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome\u2010coronavirus\u20102 infection often results from alveolar injury that impedes airway capacity and multi\u2010organ failure\u2014both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL\u20106, IL\u20101\u03b2, IL\u201010, TNF, GM\u2010CSF, IP\u201010 (IFN\u2010induced protein 10), IL\u201017, MCP\u20103, and IL\u20101ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID\u201019) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID\u201019 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID\u201019, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "qid": 39, "docid": "r4vobu5w", "rank": 24, "score": 11.313499450683594}, {"content": "Title: Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19 Content: In December 2019, a novel coronavirus pneumonia (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly broke out in China and rapidly spread all over the world. Recently, a cell surface protein, known as angiotensin-converting enzyme II (ACE2), has been identified to be involved in receptor-mediated endocytosis for SARS-CoV-2 entry to the cells. Many studies have reported the clinical characteristics of COVID-19: sudden deterioration of disease around 1-2 weeks after onset; much lower level of lymphocytes, especially natural killer (NK) cells in peripheral blood; extremely high pro-inflammatory cytokines and C reactive protein (CRP). About 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. Baricitinib intracellularly inhibits the proinflammatory signal of several cytokines by suppressing Janus kinase (JAK) JAK1/JAK2. It has been demonstrated clinical benefits for the patients with rheumatoid arthritis (RA), active systemic lupus erythematosus and atopic dermatitis with good efficacy and safety records. Baricitinib is expected to interrupt the passage and intracellular assembly of SARS-CoV-2 into the target cells mediated by ACE2 receptor, and treat cytokine storm caused by COVID-19. Several clinical trials are currently investigating the drug, and one of which has been completed with encouraging results. In this paper, we will elaborate the role of cytokine storm mediated by JAK-STAT pathway in severe COVID-19, the possible mechanisms of baricitinib on reducing the viral entry into the target cells and cytokine storm, the key points of pharmaceutical care based on the latest research reports, clinical trials progress and drug instruction from the US FDA, so as to provide reference for the treatment of severe COVID-19.", "qid": 39, "docid": "8mei3fqy", "rank": 25, "score": 11.20989990234375}, {"content": "Title: Traditional Chinese medicine for treatment of COVID-19 based on literature mining of targeting cytokine storm/ \u57fa\u4e8e\u5e72\u9884\u7ec6\u80de\u56e0\u5b50\u98ce\u66b4\u6587\u732e\u6316\u6398\u7684\u4e2d\u533b\u836f\u6cbb\u7597\u91cd\u75c7\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u63a2\u8ba8 Content: The primary clinical manifestations of coronavirus disease 2019 (COVID-19) are fever, fatigue and dry cough. Several clinical studies reported that some patients with low or medium fever, or even without obvious symptom, rapidly progressed to severe or critical illness, including severe acute respiratory syndrome, septic shock, coagulation disorders and intractable metabolic acidosis. These patients were usually associated with significant elevated serum levels of a profile of cytokines, which is similar to SARS-2003 and MERS-2015, indicating the occurrence of cytokine storm. In the present review, we summarized previous advances in the treatment of severe cases of SARS by using traditional Chinese medicines (TCM), especially those TCM targeting cytokine storm, based on literature mining. By using data mining and network pharmacology, we also investigated underlying mechanisms and biological pathways involved in the inhibitory effects of TCM against cytokine storm. This review not only provides novel insights in the precise application of TCM, appropriate integrative use of TCM in combination with western medicine, but also contributes to the discovery of novel drugs or new therapeutic strategies targeting cytokine storm to suppress progression of COVID-19 and to improve clinical prognosis and outcomes.", "qid": 39, "docid": "ph3z1ha4", "rank": 26, "score": 11.111000061035156}, {"content": "Title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. KEY MESSAGES: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "qid": 39, "docid": "lnltoj1n", "rank": 27, "score": 11.059900283813477}, {"content": "Title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "qid": 39, "docid": "re7ar8b1", "rank": 28, "score": 11.05989933013916}, {"content": "Title: Potential for jaktinib hydrochloride to treat cytokine storms in patients with COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a serious public health threat to the whole world, and the number of infected is still rising dramatically at this moment. Several studies have confirmed that cytokine storms play a critical role in causing a case to worsen from mild to severe or critical. The current treatment for cytokine storms is limited, so the international medical community is focusing on a specific and effective remedy. Jaktinib hydrochloride is a broad spectrum JAK inhibitor. It can inhibit cytokine-induced immune activation by multiple mechanisms and also slow viral proliferation by inhibiting AAK1 without causing unacceptable toxicity. Jaktinib hydrochloride has great potential for the treatment of patients with coronavirus disease 2019 (COVID-19).", "qid": 39, "docid": "69884505", "rank": 29, "score": 11.002599716186523}, {"content": "Title: Potential for jaktinib hydrochloride to treat cytokine storms in patients with COVID-19. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a serious public health threat to the whole world, and the number of infected is still rising dramatically at this moment. Several studies have confirmed that cytokine storms play a critical role in causing a case to worsen from mild to severe or critical. The current treatment for cytokine storms is limited, so the international medical community is focusing on a specific and effective remedy. Jaktinib hydrochloride is a broad spectrum JAK inhibitor. It can inhibit cytokine-induced immune activation by multiple mechanisms and also slow viral proliferation by inhibiting AAK1 without causing unacceptable toxicity. Jaktinib hydrochloride has great potential for the treatment of patients with coronavirus disease 2019 (COVID-19).", "qid": 39, "docid": "a1m11gx9", "rank": 30, "score": 11.002598762512207}, {"content": "Title: Pirfenidone: A novel hypothetical treatment for COVID-19 Content: Cytokine storm, multiorgan failure, and particularly acute respiratory distress syndrome (ARDS) is the leading cause of mortality and morbidity in patients with COVID-19. A fulminant ARDS kills the majority of COVID-19 victims. Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), is a novel anti-fibrotic agent with trivial adverse effects. Pirfenidone is approved for the treatment of Idiopathic Pulmonary Fibrosis (IPF) for patients with mild to moderate disease. Pirfenidone could inhibit apoptosis, downregulate ACE receptors expression, decrease inflammation by several mechanisms and ameliorate oxidative stress and hence protect pneumocytes and other cells from COVID-19 invasion and cytokine storm simultaneously. Based on the pirfenidone mechanism of action and the known pathophysiology of COVID-19, I believe that pirfenidone has the potential for the treatment of COVID-19 patients.", "qid": 39, "docid": "ru2mxne1", "rank": 31, "score": 10.934900283813477}, {"content": "Title: COVID-19: Consider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS-CoV-2 infected patients Content: COVID-19 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. To reduce the cytokine storm, we would like to propose the interleukin (IL) 6 receptor (IL-6R) antagonist therapy for the COVID-19 patients. Two humanized monoclonal antibodies are in clinical trial following IL-6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL-6R antagonists for the therapy of cytokine storm syndrome severe acute respiratory syndrome coronavirus 2 infected persons to enhance the therapeutic options for cytokine storm.", "qid": 39, "docid": "wbk2q4aj", "rank": 32, "score": 10.882499694824219}, {"content": "Title: Recovery of COVID-19 acute respiratory distress syndrome with tocilizumab: successful outcome in two critically ill patients Content: Background: Severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 is a challenge for nowadays medical practice. Although there is no clarity in the principal mechanism of lung damage and ARDS development, it has been suggested that one of the main reasons of this pathology is the hyperactivation of the immune system, better known as cytokine storm syndrome. Tocilizumab has been proposed to treat COVID-19 severe cases associated to ARDS. Results & methodology: Here we present two successful cases of tocilizumab administration in two COVID-19 patients with prior administration of antiviral therapy (hydroxychloroquine, azithromycin, lopinavir and ritonavir) with adequate response and resolution of ARDS, septic shock and severe pneumonia within the first 72 h. Discussion & conclusion: This case supports the usage of tocilizumab as an effective therapy in COVID-19 associated cytokine storm syndrome. Further studies should be done in order to assess its effectiveness and security.", "qid": 39, "docid": "6lr8i54a", "rank": 33, "score": 10.864299774169922}, {"content": "Title: Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 Content: Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.", "qid": 39, "docid": "2u5zxc2i", "rank": 34, "score": 10.804100036621094}, {"content": "Title: COVID\u201019: Consider IL6 receptor antagonist for the therapy of cytokine storm syndrome in SARS\u2010CoV\u20102 infected patients Content: COVID\u201019 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. In order to reduce the cytokine storm, we would like to propose the IL6 receptor antagonist therapy for the COVID\u201019 patients. Two humanized monoclonal antibodies are in clinical trial following IL6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL6 receptor antagonists for the therapy of cytokine storm syndrome SARS\u2010CoV\u20102 infected persons to enhance the therapeutic options for cytokine storm. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "b30nkhcs", "rank": 35, "score": 10.74590015411377}, {"content": "Title: Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients. Content: COVID-19, the illness caused by infection with the novel coronavirus SARS-CoV-2, is a rapidly spreading global pandemic in urgent need of effective treatments. Here we present a comprehensive examination of the host- and virus-targeted functions of the flavonolignan silibinin, a potential drug candidate against COVID-19/SARS-CoV-2. As a direct inhibitor of STAT3-a master checkpoint regulator of inflammatory cytokine signaling and immune response-silibinin might be expected to phenotypically integrate the mechanisms of action of IL-6-targeted monoclonal antibodies and pan-JAK1/2 inhibitors to limit the cytokine storm and T-cell lymphopenia in the clinical setting of severe COVID-19. As a computationally predicted, remdesivir-like inhibitor of RNA-dependent RNA polymerase (RdRp)-the central component of the replication/transcription machinery of SARS-CoV-2-silibinin is expected to reduce viral load and impede delayed interferon responses. The dual ability of silibinin to target both the host cytokine storm and the virus replication machinery provides a strong rationale for the clinical testing of silibinin against the COVID-19 global public health emergency. A randomized, open-label, phase II multicentric clinical trial (SIL-COVID19) will evaluate the therapeutic efficacy of silibinin in the prevention of acute respiratory distress syndrome in moderate-to-severe COVID-19-positive onco-hematological patients at the Catalan Institute of Oncology in Catalonia, Spain.", "qid": 39, "docid": "ci7eybs8", "rank": 36, "score": 10.708600044250488}, {"content": "Title: On the Alert for Cytokine Storm: Immunopathology in COVID-19 Content: Poor outcomes in COVID-19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID-19.", "qid": 39, "docid": "6io0zd0z", "rank": 37, "score": 10.701499938964844}, {"content": "Title: On the Alert for Cytokine Storm: Immunopathology in COVID\u201019 Content: Poor outcomes in COVID\u201019 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID\u201019.", "qid": 39, "docid": "y26r9g3m", "rank": 38, "score": 10.701498985290527}, {"content": "Title: Favorable COVID-19 course despite significant comorbidities in a ruxolitinib-treated patient with primary myelofibrosis Content: COVID-19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID-19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental \"cytokine storm\", such as Janus-activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55-yo patient with proven COVID-19 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in-label for co-existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID-19. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient\u00b4s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS-CoV-2 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID-19 pneumonia, preventing cytokine storm and ARDS.", "qid": 39, "docid": "q5eor7hh", "rank": 39, "score": 10.660699844360352}, {"content": "Title: Favorable COVID\u201019 course despite significant comorbidities in a ruxolitinib\u2010treated patient with primary myelofibrosis Content: COVID\u201019 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID\u201019 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental \u201ccytokine storm\u201d, such as Janus\u2010activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55\u2010yo patient with proven COVID\u201019 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in\u2010label for co\u2010existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID\u201019. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient\u00b4s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS\u2010CoV\u20102 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID\u201019 pneumonia, preventing cytokine storm and ARDS.", "qid": 39, "docid": "udyfm2bn", "rank": 40, "score": 10.660698890686035}, {"content": "Title: COVID-19 and the Heart Content: Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 39, "docid": "dn41mqmb", "rank": 41, "score": 10.61299991607666}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 39, "docid": "fqlv35vo", "rank": 42, "score": 10.603699684143066}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 39, "docid": "iaatjew2", "rank": 43, "score": 10.60369873046875}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection. Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 39, "docid": "5rc9x979", "rank": 44, "score": 10.561300277709961}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 39, "docid": "vt56yqel", "rank": 45, "score": 10.561299324035645}, {"content": "Title: Amelioration of COVID\u201019 related cytokine storm syndrome: Parallels to chimeric antigen receptor\u2010T cell cytokine release syndrome Content: Coronavirus disease\u20102019 (COVID\u201019) severity appears to parallel the host immune response, with a subset of patients developing COVID\u201019 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID\u201019,(2\u20135) and interleukin (IL)\u20106 appears to play a central role in COVID\u201019 related CSS.(6\u20138) Based on the success of IL\u20106 receptor blockade for chimeric antigen receptor T\u2010cell therapy associated cytokine release syndrome (CAR T\u2010cell CRS), similar strategies using tocilizumab are being investigated in COVID\u201019.", "qid": 39, "docid": "i757oxb6", "rank": 46, "score": 10.456700325012207}, {"content": "Title: Amelioration of COVID-19 related cytokine storm syndrome: Parallels to chimeric antigen receptor-T cell cytokine release syndrome Content: Coronavirus disease-2019 (COVID-19) severity appears to parallel the host immune response, with a subset of patients developing COVID-19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID-19,(2-5) and interleukin (IL)-6 appears to play a central role in COVID-19 related CSS.(6-8) Based on the success of IL-6 receptor blockade for chimeric antigen receptor T-cell therapy associated cytokine release syndrome (CAR T-cell CRS), similar strategies using tocilizumab are being investigated in COVID-19.", "qid": 39, "docid": "jxsj3lg6", "rank": 47, "score": 10.45669937133789}, {"content": "Title: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin Content: Some of the articles being published during the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined 'hyperferritinemic syndrome', which already includes adult-onset Still's disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.", "qid": 39, "docid": "l95x70ab", "rank": 48, "score": 10.45479965209961}, {"content": "Title: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin Content: Some of the articles being published during the severe acute respiratory syndrome\u2013coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined \u2018hyperferritinemic syndrome\u2019, which already includes adult-onset Still\u2019s disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.", "qid": 39, "docid": "qth1y88o", "rank": 49, "score": 10.454798698425293}, {"content": "Title: Immune Status of COVID-19 Patients with Reference to SARS and MERS Content: During this global pandemic of COVID-19 infection, it became well known that morbidity and mortality is especially high at the extreme of life especially in certain racial or ethnic groups like Americans and Africans This is presumed due to low immunity associated with other comorbid conditions like diabetes, hypertension, cardiovascular disease, obesity and metabolic syndrome But the information available on the immune status of COVID-19 patients is limited Attempts must be made to enhance our understanding of the immune status of COVID-19 patients by revisiting our knowledge on the immune mechanisms of already known coronaviruses such as SARS-CoV and MERS-CoV Early elevation of the serum levels of pro-inflammatory cytokines observed in SARS and MERS infection suggests a possible same type of cytokine storm-mediated lung damage in COVID-19 patients too Dysregulation of interferon-1 response and downstream cascade in initial innate immune response at virus entry point has been related to lethal pneumonia in COVID-19 patients Adaptive response of increased CD8+ levels in COVID-19 patients seems to be useful in mild cases where it causes deteriorating effects in progressed severe disease patients resulting in destruction of type 2 pneumocytes hence inability to regenerate the alveolar epithelium A phenomenon called cytokine storm activates violent immunological reactions in the lung tissue resulting in ARDS followed by multiple organ system damages in COVID-19 patients Several immune evading mechanisms are thought to be employed by severe respiratory syndrome virus-2 (SARS-CoV-2) that might have resulted in its extremely increased contagiousness probably related with its frequent RNA mutations Failure to develop adequate virus limiting immune reactions by some cured patients warrant monitoring of all recovered patients This rapid mini review is aimed to enhance our knowledge of the immune status of COVID-19 infected patients with reference to SARS-CoV and MERS-CoV", "qid": 39, "docid": "f37cp6j3", "rank": 50, "score": 10.449399948120117}, {"content": "Title: SARS-CoV-2: Viral Mechanisms and Possible Therapeutic Targets - What to learn from Rheumatologists? Content: It was with great interest that we read the letter from Randy Cron and collaborators (1) linking the cytokine storm syndrome (CSS) seen in macrophage activation syndrome, common in the rheumatological setting, with the CSS postulated to be a background in the novel coronavirus (SARS-CoV-2) infection. Amid the high contagiousness of the virus, science was also infected by an infodemia, compelled to enter a race to find effective therapies studying mechanisms molecular aspects of SARS-CoV-2 concomitant to urgent bedside manage of patients.", "qid": 39, "docid": "55n1ttz4", "rank": 51, "score": 10.434000015258789}, {"content": "Title: Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic Content: Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: \"hemophagocytic syndrome\" OR \"macrophage activation syndrome\" OR \"hemophagocytic lymphohistiocytosis\", OR \"cytokine storm\". Finally, AND \"COVID-19\" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of \"Hemophagocytic syndrome\" OR \"Macrophage activation syndrome\" OR \"Hemophagocytic lymphohistiocytosis\" OR \"Cytokine storm\" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND \"COVID-19\") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.", "qid": 39, "docid": "azy3uf6m", "rank": 52, "score": 10.42959976196289}, {"content": "Title: Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic Content: Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: \u201chemophagocytic syndrome\u201d OR \u201cmacrophage activation syndrome\u201d OR \u201chemophagocytic lymphohistiocytosis\u201d, OR \u201ccytokine storm\u201d. Finally, AND \u201cCOVID-19\u201d was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of \u201cHemophagocytic syndrome\u201d OR \u201cMacrophage activation syndrome\u201d OR \u201cHemophagocytic lymphohistiocytosis\u201d OR \u201cCytokine storm\u201d yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND \u201cCOVID-19\u201d) resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.", "qid": 39, "docid": "fqobpo47", "rank": 53, "score": 10.429598808288574}, {"content": "Title: Severe COVID-19 and aging: are monocytes the key? Content: The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation\u2013related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.", "qid": 39, "docid": "ch7pjb70", "rank": 54, "score": 10.347200393676758}, {"content": "Title: Severe COVID-19 and aging: are monocytes the key? Content: The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation-related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.", "qid": 39, "docid": "uiffwx65", "rank": 55, "score": 10.347199440002441}, {"content": "Title: COVID-19 and the Heart. Content: Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 39, "docid": "d4h49d8b", "rank": 56, "score": 10.340999603271484}, {"content": "Title: Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome Content: The mortality of Coronavirus disease 2019 (COVID-19) appears to be driven by acute respiratory distress syndrome (ARDS) and a dysregulated immune response to SARS-CoV-2. Emerging evidence suggests that a subset of COVID-19 is characterized by the development of a cytokine storm syndrome (CSS), and interleukin (IL)-6 levels are predictors of COVID-19 severity and in-hospital mortality. Targeting hyper-inflammation in COVID-19 may be critical for reducing mortality. Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (\u03b11-AR) signaling. Prophylactic inhibition of catecholamine synthesis with the \u03b11-AR antagonist prazosin reduced catecholamines and cytokine responses in mice, and resulted in markedly increased survival following various hyper-inflammatory stimuli. These findings offer a rationale for studying \u03b11-AR antagonists in the prophylaxis of patients with COVID-19-CSS and ARDS. As high infection rates threaten to overwhelm hospital capacity during this pandemic, preventative approaches that ameliorate COVID-19 severity and reduce excessive mortality are desperately needed. We hypothesize that treatment with prazosin of individuals who test positive for SARS-CoV-2 could reduce catecholamine surges, secondary cytokine dysregulation, and mortality. To investigate a potential role for \u03b11-AR antagonists in preventing poor outcomes in ARDS, we conducted a retrospective analysis of hospitalized patients diagnosed with ARDS. Using data from the Truven Health MarketScan Research Database (2010-2017), we identified 13,125 men (age 45-64) with ARDS, of whom 655 patients (5.0%) were prescribed \u03b11-AR antagonists in the previous year. Applying logistic regression models, we found that patients with prior use of \u03b11-AR antagonists had lower odds of invasive mechanical ventilation compared to non-users (adjusted OR=0.75, 95% CI 0.59-0.95, p=0.019). Perhaps more importantly, those patients had a ~36% lower incidence of both being ventilated and dying in the hospital (adjusted OR=0.59, 95% CI 0.34-0.95, p=0.042). By contrast, prior use of beta-adrenergic receptor (\u03b2-AR) antagonists was not correlated with either outcome. We extended these analyses to patients admitted with pneumonia. Of 108,956 subjects in this cohort, 5,498 patients (5.0%) were taking \u03b11-AR antagonist. Similar to ARDS, patients with pneumonia on \u03b11-AR antagonists (but no \u03b2-AR antagonists) had a lower odds of mechanical ventilation (adjusted OR=0.83, 95% CI 0.75-0.92, p<0.001) and of both being ventilated and dying in the hospital (adjusted OR=0.77, 95% CI 0.62-0.94, p=0.014) compared to non-users. Mirroring findings from pre-clinical models, these data support a clinical rationale to study \u03b11-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19. Prospective, randomized clinical trials of alpha-1 receptor antagonists (e.g. prazosin) administered prior to the onset of severe symptoms are needed to assess their efficacy in preventing CSS and reducing mortality in COVID-19.", "qid": 39, "docid": "0lwmzjxz", "rank": 57, "score": 10.331399917602539}, {"content": "Title: The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the \u201ccytokine storm\u201d in COVID-19 patients: a hypothesis Content: BACKGROUND: A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a \u201ccytokine storm\u201d. While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm. PRESENTATION OF THE HYPOTHESIS: A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures. TESTING THE HYPOTHESIS: A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration. IMPLICATIONS OF HYPOTHESIS: If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit. CONCLUSIONS: In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.", "qid": 39, "docid": "uxuvirv7", "rank": 58, "score": 10.32289981842041}, {"content": "Title: Posterior Reversible Encephalopathy Syndrome: A Manifestation of COVID-19 Cytokine Storm Content: Neuroimaging manifestations of COVID-19 are being reported with increasing frequency with recent reports of associated atypical leukoencephalopathies. We add to this literature by describing a COVID-19 + patient who demonstrated imaging findings typical for posterior reversible encephalopathy syndrome (PRES). The inflammatory syndrome associated with novel corona virus infection has shown markedly increased levels of cytokines and inflammatory markers. This has also been described in a proposed mechanism for PRES, where elevated inflammatory markers result in endothelial injury causing interstitial fluid extravasation typical of PRES. We expect that other cases of PRES will be observed in this population given the scope of the Covid-19 pandemic.", "qid": 39, "docid": "3tdj1yy5", "rank": 59, "score": 10.313400268554688}, {"content": "Title: 2019 Novel Coronavirus Pandemic: What Do We Know? Content: The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome It may be complicated by septic shock and subsequent multi-organ failure Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines", "qid": 39, "docid": "8lnb2tnz", "rank": 60, "score": 10.251399993896484}, {"content": "Title: 2019 Novel Coronavirus Pandemic: What Do We Know? Content: The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.", "qid": 39, "docid": "k3w39apy", "rank": 61, "score": 10.251399040222168}, {"content": "Title: Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19 Content: The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called \u201ccytokine storm\u201d. Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-\u03b1, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-\u03b1, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.", "qid": 39, "docid": "brmmpwls", "rank": 62, "score": 10.24470043182373}, {"content": "Title: Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19 Content: The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called \"cytokine storm\". Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-&#945;, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-&#945;, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.", "qid": 39, "docid": "gf0p6g7w", "rank": 63, "score": 10.244699478149414}, {"content": "Title: Adjunct immunotherapies for the management of severely ill COVID-19 patients Content: Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has infected millions with more than 181,000 fatal cases as of 22nd April 2020. Currently, there are no specific COVID-19 therapies. Most patients depend on mechanical ventilation. Current COVID-19 data clearly highlight that cytokine storm and activated immune cell migration to the lungs characterize the early immune response to COVID-19 that causes severe lung damage and development of acute respiratory distress syndrome. In view of uncertainty associated with immunosuppressive treatments such as corticosteroids and their possible secondary effects, including risks of secondary infections, we suggest immunotherapies as an adjunct therapy in severe COVID-19 cases. Such immunotherapies based on inflammatory cytokine neutralization, immunomodulation and passive viral neutralization, not only reduce inflammation, inflammation-associated lung damage, or viral load, but could also prevent intensive care unit hospitalization and dependency on mechanical ventilation both of which are limited resources.", "qid": 39, "docid": "3uodkrkp", "rank": 64, "score": 10.237500190734863}, {"content": "Title: Adjunct Immunotherapies for the Management of Severely Ill COVID-19 Patients Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has infected millions, with more than 275,000 fatal cases as of May 8, 2020. Currently, there are no specific COVID-19 therapies. Most patients depend on mechanical ventilation. Current COVID-19 data clearly highlight that cytokine storm and activated immune cell migration to the lungs characterize the early immune response to COVID-19 that causes severe lung damage and development of acute respiratory distress syndrome. In view of uncertainty associated with immunosuppressive treatments, such as corticosteroids and their possible secondary effects, including risks of secondary infections, we suggest immunotherapies as an adjunct therapy in severe COVID-19 cases. Such immunotherapies based on inflammatory cytokine neutralization, immunomodulation, and passive viral neutralization not only reduce inflammation, inflammation-associated lung damage, or viral load but could also prevent intensive care unit hospitalization and dependency on mechanical ventilation, both of which are limited resources.", "qid": 39, "docid": "7j7wiylq", "rank": 65, "score": 10.237499237060547}, {"content": "Title: COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons Content: The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic. Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome. Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality. To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients. This review evaluates several options that have been proposed to control SARS-CoV2 hyperinflammation and cytokine storm, eincluding antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).", "qid": 39, "docid": "y4kohxgy", "rank": 66, "score": 10.23169994354248}, {"content": "Title: Considerations for Statin Therapy in Patients with COVID\u201019 Content: Current coronavirus pandemic named coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is the third coronavirus outbreak during the current century after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses.1 Acute respiratory distress syndrome (ARDS) is an immunopathologic event and main cause of death following COVID-19. The main mechanism of ARDS is uncontrolled systemic inflammatory response and cytokine storm following release of proinflammatory cytokines (such as interferons (IFN), interleukines (IL), tumor necrosis factor (TNF)-\u03b1) and chemokines.2-3 So, some Chinese researchers proposed or used anti-inflammatory agents in the treatment regimen of patients with COVID-19.3-4.", "qid": 39, "docid": "3fp46sov", "rank": 67, "score": 10.221599578857422}, {"content": "Title: Covid-19 nephropathy: What could pathologist say? Content: Implication for health policy/practice/research/medical education: The pathogenetic mechanism of renal involvement in coronavirus disease 19 (COVID-19) is still unclear. It is supposed to result from a combination of several contributing factors, such as state of dehydration, leading to pre-renal failure with acute tubular necrosis, toxic tubular damage, induced by cytokine storm or rhabdomyolysis, cytopathic action induced by the virus that invades ACE2- expressing kidney cells and drug-induced nephrotoxicity.", "qid": 39, "docid": "6f2xb5m7", "rank": 68, "score": 10.206399917602539}, {"content": "Title: Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial Content: INTRODUCTION: The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19. METHODS AND ANALYSIS: The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04264533.", "qid": 39, "docid": "9eug7szt", "rank": 69, "score": 10.190600395202637}, {"content": "Title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy Content: Cytokine storms are drivers of pathology and mortality in myriad viral infections affecting the human population. In SARS-CoV-2-infected patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress syndrome, myocardial damage, and death. However, the therapeutic value of attenuating the cytokine storm in COVID-19 remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome (DS) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity, accompanying cytokine storm, and liver hyperinflammation are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic. One Sentence Summary Inhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice.", "qid": 39, "docid": "yabt72jf", "rank": 70, "score": 10.176199913024902}, {"content": "Title: Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19 Content: COVID-19 is rapidly spreading contagious disease spreading across the world. Patients at risk are elderly people and those with comorbidity. Early studies done on Chinese patients who suggest cytokine storm to be responsible for lung injury. We need to understand the mechanism of modulating such robust response of immunity and resultant cytokine storm. We suggest nicotinamide, a potential poly ADP ribose polymerase (PARP) inhibitor, as a supportive treatment for the prevention of cytokine storm from injuring the lung parenchyma. Nicotinamide supplementation albeit at high dose may modulate outcome in COVID-19. Nicotinamide was used previously to reduce ventilator-induced lung injury and lung injury due to hypoxia. Nicotinamide congeners are used to treat chronic lung disease like tuberculosis. Certainly, nicotinamide is effective pharmacotherapy in lung injury \u2013 whether acute or chronic. Other measures used in treating COVID-19 are focusing on targeting interleukin-6 \u2013 a cytokine responsible for mayhem, while few are targeting granulocyte-macrophage colony- stimulating factor. We suggest targeting PARP in addition to other measures to block cytokines. By inhibiting PARP course of COVID-19 may be altered. Understanding the pathophysiology of acute lung injury is crucial. PARP plays a pivotal role on cytokine release in response to any lung injury ranging from viral infection to hypoxia. Various antiviral defenses and immune response need to be studied in detail.", "qid": 39, "docid": "1kv12oj0", "rank": 71, "score": 10.116100311279297}, {"content": "Title: Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use Content: COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis 1. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.", "qid": 39, "docid": "aplbtvfd", "rank": 72, "score": 10.100299835205078}, {"content": "Title: Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use. Content: COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis\u20261. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.", "qid": 39, "docid": "e98a5ed5", "rank": 73, "score": 10.100298881530762}, {"content": "Title: Successful recovery of severe COVID-19 with cytokine storm treating with extracorporeal blood purification Content: COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.", "qid": 39, "docid": "zjxey3po", "rank": 74, "score": 10.087300300598145}, {"content": "Title: Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes Content: A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a \"Cytokine Storm Syndrome\" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "qid": 39, "docid": "2b6l1c0n", "rank": 75, "score": 10.086700439453125}, {"content": "Title: Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes Content: A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a \u201cCytokine Storm Syndrome\u201d (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "qid": 39, "docid": "9321dl89", "rank": 76, "score": 10.086699485778809}, {"content": "Title: Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy? Content: In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In \"chronic inflammatory diseases\", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.", "qid": 39, "docid": "xhr9i6gw", "rank": 77, "score": 10.062899589538574}, {"content": "Title: Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors Content: The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the \u2018cytokine storm\u2019, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1\u03b2, IL-6 and TNF-\u03b1 secretion via \u2018trained monocytes\u2019, which confers early protection against SARS-CoV2.", "qid": 39, "docid": "6dq6gm27", "rank": 78, "score": 10.059700012207031}, {"content": "Title: Lymphopenia in COVID-19: Therapeutic opportunities Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS-CoV-2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.", "qid": 39, "docid": "cmq2832d", "rank": 79, "score": 9.944100379943848}, {"content": "Title: Lymphopenia in COVID\u201019: Therapeutic opportunities Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS\u2010CoV\u20102, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.", "qid": 39, "docid": "ep9aqpfs", "rank": 80, "score": 9.944099426269531}, {"content": "Title: Cytokine storm in COVID\u201019 and parthenolide: preclinical evidence Content: A group of patients with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) were reported from China in December 2019. Although several antiviral drugs are widely tested, none of them has been approved as specific antiviral therapy for coronavirus disease 2019 (COVID\u201019). Accumulating evidence established a hyperinflammatory states or cytokine storm in COVID\u201019. Among these cytokines, IL\u20106 plays a key role in cytokine storm and can predict the adverse clinical outcomes and fatality in these patients. Based on the evidence of the significant role of IL\u20106 in cytokine storm, diabetes mellitus and cardiovascular diseases as principal comorbidities, it seems that anti\u2010cytokine therapy may be useful in patients with severe COVID\u201019 to reduce mortality. Recent studies demonstrated that herbal\u2010derived natural products had immunosuppressive and anti\u2010inflammatory properties and exhibited exceptional act on mediators of inflammation. Parthenolide is the principal sesquiterpene lactones and the main biologically active constituent Tanacetum parthenium (commonly known as feverfew) which has could significantly reduce IL\u20101, IL\u20102, IL\u20106, IL\u20108, and TNF\u2010\u03b1 production pathways established in several human cell line models in vitro and in vivo studies. Therefore, parthenolide may be one of the herbal candidates for clinical evaluation. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "0fgquau3", "rank": 81, "score": 9.943499565124512}, {"content": "Title: Cytokine storm in COVID-19 and parthenolide: Preclinical evidence Content: A group of patients with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported from China in December 2019. Although several antiviral drugs are widely tested, none of them has been approved as specific antiviral therapy for coronavirus disease 2019 (COVID-19). Accumulating evidence established a hyperinflammatory states or cytokine storm in COVID-19. Among these cytokines, IL-6 plays a key role in cytokine storm and can predict the adverse clinical outcomes and fatality in these patients. Based on the evidence of the significant role of IL-6 in cytokine storm, diabetes mellitus, and cardiovascular diseases as principal comorbidities, it seems that anti-cytokine therapy may be useful in patients with severe COVID-19 to reduce mortality. Recent studies demonstrated that herbal-derived natural products had immunosuppressive and anti-inflammatory properties and exhibited exceptional act on mediators of inflammation. Parthenolide is the principal sesquiterpene lactones and the main biologically active constituent Tanacetum parthenium (commonly known as feverfew) which has could significantly reduce IL-1, IL-2, IL-6, IL-8, and TNF-&#945; production pathways established in several human cell line models in vitro and in vivo studies. Therefore, parthenolide may be one of the herbal candidates for clinical evaluation.", "qid": 39, "docid": "qiy1tiga", "rank": 82, "score": 9.943498611450195}, {"content": "Title: Cytokine storm intervention in the early stages of COVID-19 pneumonia Content: Abstract Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.", "qid": 39, "docid": "5bmdzgla", "rank": 83, "score": 9.932600021362305}, {"content": "Title: Cytokine storm intervention in the early stages of COVID-19 pneumonia Content: Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.", "qid": 39, "docid": "8a0tmn90", "rank": 84, "score": 9.932599067687988}, {"content": "Title: Inflammation: A bridge between Diabetes and COVID-19, and possible management with sitagliptin Content: Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.", "qid": 39, "docid": "8p5chz08", "rank": 85, "score": 9.911100387573242}, {"content": "Title: Preventing cytokine storm syndrome in COVID-19 using \u03b1-1 adrenergic receptor antagonists. Content: Medications that target catecholamine-associated inflammation may prevent cytokine storm syndrome associated with COVID-19 and other diseases.", "qid": 39, "docid": "9408n63a", "rank": 86, "score": 9.892900466918945}, {"content": "Title: Alpha-1 adrenergic receptor antagonists for preventing acute respiratory distress syndrome and death from cytokine storm syndrome Content: In severe viral pneumonias, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists ($\\alpha$-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia (n = 13,125 and n = 108,956, respectively) from all causes; patients who were incidentally taking $\\alpha$-blockers had a reduced risk of requiring ventilation (by 35% and 16%, respectively), and a reduced risk of being ventilated and dying (by 56% and 20%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects. These results highlight the urgent need for prospective trials testing whether prophylactic $\\alpha$-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.", "qid": 39, "docid": "44ik4p7v", "rank": 87, "score": 9.864299774169922}, {"content": "Title: Alpha-1 adrenergic receptor antagonists for preventing acute respiratory distress syndrome and death from cytokine storm syndrome. Content: In severe viral pneumonias, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists ($\\alpha$-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia (n = 13,125 and n = 108,956, respectively) from all causes; patients who were incidentally taking $\\alpha$-blockers had a reduced risk of requiring ventilation (by 35% and 16%, respectively), and a reduced risk of being ventilated and dying (by 56% and 20%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects. These results highlight the urgent need for prospective trials testing whether prophylactic $\\alpha$-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.", "qid": 39, "docid": "metnu19r", "rank": 88, "score": 9.864298820495605}, {"content": "Title: Role of oxidized LDL-induced \"trained macrophages\" in the pathogenesis of COVID-19 and benefits of pioglitazone: A hypothesis Content: BACKGROUND AND AIMS: Older adults and people who have cardiovascular disorders (their common pathogenetic mechanism is progressive atherosclerosis) are at higher risk for severe illness from COVID-19 (coronavirus disease 2019). Their common pathogenetic mechanism is progressive atherosclerosis in which oxLDL (oxidized LDL) plays major role. Receptor-mediated uptake of oxLDL by the monocyte-derived macrophages activates the long-term epigenetic reprogramming of innate immunity, which is termed \"trained immunity.\" The aim of this work is to investigate the mechanisms and treatment possibilities that can control the activities of these specific macrophages. METHODS: Search in Medline and PubMed relevant articles on the trained immunity and cytokine storm of COVID-19. RESULTS AND CONCLUSIONS: When oxLDL-trained macrophages encounter SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the lung, it causes unregulated cytokine secretion, leading to the alveolar damage. Therefore, blocking macrophage training by pioglitazone, a thiazolidinedione, could control the hyperactivation that the virus would trigger.", "qid": 39, "docid": "f3ozq201", "rank": 89, "score": 9.862000465393066}, {"content": "Title: Role of oxidized LDL-induced \u201ctrained macrophages\u201d in the pathogenesis of COVID-19 and benefits of pioglitazone: A hypothesis Content: BACKGROUND AND AIMS: Older adults and people who have cardiovascular disorders (their common pathogenetic mechanism is progressive atherosclerosis) are at higher risk for severe illness from COVID-19 (coronavirus disease 2019). Their common pathogenetic mechanism is progressive atherosclerosis in which oxLDL (oxidized LDL) plays major role. Receptor-mediated uptake of oxLDL by the monocyte-derived macrophages activates the long-term epigenetic reprogramming of innate immunity, which is termed \u201ctrained immunity.\u201d The aim of this work is to investigate the mechanisms and treatment possibilities that can control the activities of these specific macrophages. METHODS: Search in Medline and PubMed relevant articles on the trained immunity and cytokine storm of COVID-19. CONCLUSIONS: When oxLDL-trained macrophages encounter SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the lung, it causes unregulated cytokine secretion, leading to the alveolar damage. Therefore, blocking macrophage training by pioglitazone, a thiazolidinedione, could control the hyperactivation that the virus would trigger.", "qid": 39, "docid": "pzex799x", "rank": 90, "score": 9.86199951171875}, {"content": "Title: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Content: The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term \"hyperferritinemic syndromes\" and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and \"hyperferritinemic syndromes\" are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and \"hyperferritinemic syndromes\" which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions.", "qid": 39, "docid": "qvpjci4y", "rank": 91, "score": 9.842100143432617}, {"content": "Title: Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19 Content: AIMS: SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.", "qid": 39, "docid": "7ilz0gus", "rank": 92, "score": 9.787199974060059}, {"content": "Title: Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19 Content: AIMS: SARS\u2013CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS\u2013CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS\u2013Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.", "qid": 39, "docid": "vbfdxoc2", "rank": 93, "score": 9.787199020385742}, {"content": "Title: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Content: Abstract The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term \u201chyperferritinemic syndrome\u201d and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and \u201chyperferritinemic syndromes\u201d are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and \u201chyperferritinemic syndromes\u201d which would allow considering this entity as the fifth member of the spectrum of inflammatory conditions.", "qid": 39, "docid": "v7wgb6mr", "rank": 94, "score": 9.779600143432617}, {"content": "Title: Understanding the COVID\u201019 coagulopathy spectrum Content: The SARS\u2010Cov\u20102 (COVID\u201019) pandemic has already claimed over 200,000 lives. Quite early on in this pandemic, it was recognised that the virus triggers the immune system leading to a cytokine storm in some severely ill patients [1]. This hyper\u2010responsiveness has been suggested to be the predominant aetiology for clinical deterioration and mortality in patients with this infection [2]. More recently, there have been several reports of increased thrombotic events in these patients [3\u20106]. From a laboratory perspective, this hypercoagulability is reflected in the marked elevation of the fibrinolytic marker, D\u2010dimer, in almost all hospitalised COVID\u201019 patients [7]. We must, therefore, ask ourselves what is the link between the extremes of the immune system, presenting as cytokine storm, and the extremes of coagulation, presenting as arterial and venous thromboembolism?", "qid": 39, "docid": "343y63e5", "rank": 95, "score": 9.765299797058105}, {"content": "Title: Rapid Radiological Worsening and Cytokine Storm Syndrome in COVID-19 Pneumonia Content: BACKGROUND: In June 2020, a large randomised controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe coronavirus disease 2019 (COVID-19). CASE DESCRIPTION: We describe a patient with rapid worsening of COVID-19 pneumonia and its dramatic improvement under corticosteroids. DISCUSSION: Corticosteroids could be useful in patients with an inflammatory profile, considering that acute respiratory distress syndrome may be the consequence of cytokine storm syndrome. LEARNING POINTS: One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is inappropriate immunological hyperactivation. Corticosteroid therapy may be useful in these patients.", "qid": 39, "docid": "gc8770l9", "rank": 96, "score": 9.745599746704102}, {"content": "Title: Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm Content: SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this \"cytokine storm\" and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (&#945;7nAchR). Nicotine, an exogenous &#945;7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.", "qid": 39, "docid": "8o5juhgc", "rank": 97, "score": 9.736599922180176}, {"content": "Title: Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm Content: SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this \u201ccytokine storm\u201d and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (\u03b17nAchR). Nicotine, an exogenous \u03b17nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.", "qid": 39, "docid": "i8y1kwul", "rank": 98, "score": 9.73659896850586}, {"content": "Title: Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review Content: Abstract Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF\u03b1), interleukin-6 (IL-6), and IL-1\u03b2 with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNF\u03b1 and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned.", "qid": 39, "docid": "cv8r9pbl", "rank": 99, "score": 9.709600448608398}, {"content": "Title: Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality Content: Since December 2019, a viral pneumonia, named coronavirus disease 2019 (COVID-19), from Wuhan, China, has swept the world. Although the case fatality rate is not high, the number of people infected is large and there is still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. Therefore, treatment of the cytokine storm has become an important part of rescuing severe COVID-19 patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome. If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19.", "qid": 39, "docid": "rcl425pz", "rank": 100, "score": 9.697699546813965}]}
{"query": "What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur?", "hits": [{"content": "Title: Overwhelming mutations or SNPs of SARS-CoV-2: A point of caution Content: The morbidity of SARS-CoV-2 (COVID-19) is reaching 3 Million landmark causing and a serious public health concern globally and it is enigmatic how several antiviral and antibody treatments were not effective in the different period across the globe. With the drastic increasing number of positive cases around the world WHO raised the importance in the assessment of the risk of spread and understanding genetic modifications that could have occurred in the SARS-CoV-2. Using all available deep sequencing data of complete genome from all over the world (NCBI repository), we identified several hundreds of point mutations or SNPs in SARS-CoV-2 all across the genome. This could be the cause for the constant change and differed virulence with an increase in mortality and morbidity. Among the 12 different countries (one sequence from each country) with complete genome sequencing data, we noted the 47 key point mutations or SNPs located along the entire genome that might have impact in the virulence and response to different antivirals against SARS-CoV-2. In this regard, key viral proteins of spike glycoprotein, Nsp1, RdRp and the ORF8 region got heavily mutated within these 3 months via person-to-person passage. We also discuss what could be the possible cause of this rapid mutation in the SARS-CoV-2.", "qid": 40, "docid": "j8sg5n5g", "rank": 1, "score": 18.243900299072266}, {"content": "Title: SARS-CoV-2 genome evolution exposes early human adaptations Content: The set of mutations observed at the outset of the SARS-CoV-2 pandemic may illuminate how the virus will adapt to humans as it continues to spread. Viruses are expected to quickly acquire beneficial mutations upon jumping to a new host species. Advantageous nucleotide substitutions can be identified by their parallel occurrence in multiple independent lineages and are likely to result in changes to protein sequences. Here we show that SARS-CoV-2 is acquiring mutations more slowly than expected for neutral evolution, suggesting purifying selection is the dominant mode of evolution during the initial phase of the pandemic. However, several parallel mutations arose in multiple independent lineages and may provide a fitness advantage over the ancestral genome. We propose plausible reasons for several of the most frequent mutations. The absence of mutations in other genome regions suggests essential components of SARS-CoV-2 that could be the target of drug development. Overall this study provides genomic insights into how SARS-CoV-2 has adapted and will continue to adapt to humans. SUMMARY In this study we sought signals of evolution to identify how the SARS-CoV-2 genome has adapted at the outset of the COVID-19 pandemic. We find that the genome is largely undergoing purifying selection that maintains its ancestral sequence. However, we identified multiple positions on the genome that appear to confer an adaptive advantage based on their repeated evolution in independent lineages. This information indicates how SARS-CoV-2 will evolve as it diversifies in an increasing number of hosts.", "qid": 40, "docid": "ttbur07i", "rank": 2, "score": 17.43549919128418}, {"content": "Title: Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions Content: The COVID-19 pandemic has spread across the globe at an alarming rate in the last four months. However, unlike any of the previous global outbreaks the availability of hundreds of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 480 full-length (>29000 nt) sequences from the 1575 SARS-CoV-2 sequences available and identified 37 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, two of the 37 substitutions occur within highly conserved secondary structures in the 5\u2019 and 3\u2019 untranslated regions that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define 3 mutually exclusive lineages (A1, B1 and C1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.", "qid": 40, "docid": "miujzgtd", "rank": 3, "score": 17.204999923706055}, {"content": "Title: How fast does the SARS-Cov-2 virus really mutate in heterogeneous populations? Content: We introduce the problem of determining the mutational support of genes in the SARS-Cov-2 virus and estimating the distribution of mutations within different genes using small sample sizes that do not allow for accurate maximum likelihood estimation. The mutational support refers to the unknown number of sites mutated across all strains and individual samples of the SARS-Cov-2 genome; given the high cost and limited availability of real-time polymerase chain reaction (RT-PCR) test kits, especially in early stages of infections when only a small number of genomic samples (\u223c 1000s) are available that do not allow for determining the exact degree of mutations in an RNA virus that comprises roughly 30, 000 nucleotides. Nevertheless, working with small sample sets is required in order to quickly predict the mutation rate of this and other viruses and get an insight into their transformational power. Furthermore, with the small number of samples available, it is hard to estimate the mutational landscape across different age/gender groups and geographical locations which may be of great importance in assessing different risk categories and factors influencing susceptibility to infection. To this end, we use our state-of-the art polynomial estimator techniques and the Good-Turing estimator to obtain estimates based on only roughly 1, 000 samples per category. Our analysis reveals an interesting finding: the mutational support appears to be statistically more significant in patients which appear to have lower infection rates and handle the exposure with milder symptoms, such as women and people of relatively young age (\u2264 55).", "qid": 40, "docid": "or0rfxuu", "rank": 4, "score": 16.555500030517578}, {"content": "Title: Rampant C\u00e2\u0086\u0092U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 \u00d7 10-4 substitutions/site/year. Almost one-half of sequence changes were C\u00e2\u0086\u0092U transitions, with an 8-fold base frequency normalized directional asymmetry between C\u00e2\u0086\u0092U and U\u00e2\u0086\u0092C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C\u00e2\u0086\u0092U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5' U/A and 3' U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U \u00e2\u0089\u00ab A > G \u00e2\u0089\u00ab C) and low G+C contents may represent long-term effects of prolonged C\u00e2\u0086\u0092U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations.IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C\u00e2\u0086\u0092U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "qid": 40, "docid": "14pgap3r", "rank": 5, "score": 16.534799575805664}, {"content": "Title: Rampant C\u2192U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 \u00d7 10(\u22124) substitutions/site/year. Almost one-half of sequence changes were C\u2192U transitions, with an 8-fold base frequency normalized directional asymmetry between C\u2192U and U\u2192C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C\u2192U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5\u2032 U/A and 3\u2032 U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U \u226b A > G \u226b C) and low G+C contents may represent long-term effects of prolonged C\u2192U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations. IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C\u2192U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "qid": 40, "docid": "jw6kh8os", "rank": 6, "score": 16.53479766845703}, {"content": "Title: No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2 Content: The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that some lineages of SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible candidate mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we developed a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a carefully curated set of recurrent mutations identified within a dataset of over 23,000 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent SARS-CoV-2 mutations currently in circulation appear to be evolutionary neutral. Recurrent mutations also seem primarily induced by the human immune system via host RNA editing, rather than being signatures of adaption to the novel human host. We find no evidence at this stage for the emergence of more transmissible lineages of SARS-CoV-2 due to recurrent mutations.", "qid": 40, "docid": "a51vkiei", "rank": 7, "score": 16.48080062866211}, {"content": "Title: Sarbecovirus comparative genomics elucidates gene content of SARS-CoV-2 and functional impact of COVID-19 pandemic mutations Content: Despite its overwhelming clinical importance for understanding and mitigating the COVID-19 pandemic, the protein-coding gene content of the SARS-CoV-2 genome remains unresolved, with the function and even protein-coding status of many hypothetical proteins unknown and often conflicting among different annotations, thus hindering efforts for systematic dissection of its biology and the impact of recent mutations. Comparative genomics is a powerful approach for distinguishing protein-coding versus non-coding functional elements, based on their characteristic patterns of change, which we previously used to annotate protein-coding genes in human, fly, and other species. Here, we use comparative genomics to provide a high-confidence set of SARS-CoV-2 protein-coding genes, to characterize their protein-level and nucleotide-level evolutionary constraint, and to interpret the functional implications for SARS-CoV-2 mutations acquired during the current pandemic. We select 44 complete Sarbecovirus genomes at evolutionary distances well-suited for protein-coding and non-coding element identification, create whole-genome alignments spanning all named and putative genes, and quantify their protein-coding evolutionary signatures using PhyloCSF and their overlapping constraint using FRESCo. We find strong protein-coding signatures for all named genes and for hypothetical ORFs 3a, 6, 7a, 7b, and 8, indicating protein-coding roles, and provide strong evidence of protein-coding status for a recently-proposed alternate-frame novel ORF within 3a. By contrast, ORF10 shows no protein-coding signatures but shows unusually-high nucleotide-level constraint, indicating it has important but non-coding functions, and ORF14 and SARS-CoV-1 ORF3b, which overlap other genes, lack evolutionary signatures expected for dual-coding regions, indicating they do not produce functional proteins. ORF9b has ambiguous protein-coding signatures, preventing us from resolving its protein-coding status. ORF8 shows extremely fast nucleotide-level evolution, lacks a known function, and was deactivated in SARS-CoV-1, but shows clear signatures indicating protein-coding function worthy of further investigation given its rapid evolution and potential role in replication. SARS-CoV-2 mutations are preferentially excluded from evolutionarily-constrained amino acid residues and synonymously-constrained nucleotides, indicating purifying constraint acting at both coding and non-coding levels. In contrast, we find a conserved region in the nucleocapsid that is enriched for recent mutations, which could indicate a selective signal, and find that several spike-protein mutations previously identified as candidates for increased transmission and several mutations in isolates found to generate higher viral load in-vitro disrupt otherwise-perfectly-conserved amino-acids, consistent with adaptations for human-to-human transmission.", "qid": 40, "docid": "pxllq02w", "rank": 8, "score": 16.121299743652344}, {"content": "Title: Quantification of Intra-Host Genomic Diversity of SARS-CoV-2 Allows a High-Resolution Characterization of Viral Evolution and Reveals Functionally Convergent Variants Content: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. our approach accounts for accumulation of clonal mutations and uncertainty in the data, by taking advantage of the achievements of research in cancer evolution, to deliver robust phylogenomic lineage models, and exploits intra-host variant frequency profiles to characterize the sublineage similarity among samples, which may derive from uncovered infection events. The application of our approach to RNA-sequencing data of 162 SARS-CoV-2 samples generates a high-resolution model of evolution and spread, which improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, revealing likely infection paths among hosts harboring the same viral lineage. The in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and identifies a number of variants that are transiting from minor to clonal state in the population. We also show that standard phylogenetic methods can produce unreliable results when handling datasets with noise and sampling limitations, as proven by the further application of VERSO to 12419 consensus sequences included in GISAID database. Notably, VERSO allows to pinpoint minor variants that might be positively or negatively selected across distinct lineages, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on independent samples, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. Finally, we here release the likely SARS-CoV-2 ancestral genome, obtained by resolving ambiguous SNPs that distinguish two widely-used reference genomes from human samples, by employing the Pangolin-CoV and the Bat-CoV-RaTG13 genomes. Our results show that the joint application of our framework and data-driven epidemiological models might allow to deliver a high-resolution platform for pathogen surveillance and analysis.", "qid": 40, "docid": "ea78sjcs", "rank": 9, "score": 15.945599555969238}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "qid": 40, "docid": "bawgldfi", "rank": 10, "score": 15.909600257873535}, {"content": "Title: Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco Content: COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "qid": 40, "docid": "zb1pzdd0", "rank": 11, "score": 15.892200469970703}, {"content": "Title: Snapshot of the evolution and mutation patterns of SARS-CoV-2 Content: The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.", "qid": 40, "docid": "5od0tegt", "rank": 12, "score": 15.655699729919434}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019\u201312/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "qid": 40, "docid": "59492sjb", "rank": 13, "score": 15.498100280761719}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "qid": 40, "docid": "vahud6o5", "rank": 14, "score": 15.498099327087402}, {"content": "Title: Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations Content: In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variant sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed certain genotypes specific to the geographic location. We also found co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.", "qid": 40, "docid": "5mh3ds6y", "rank": 15, "score": 15.454899787902832}, {"content": "Title: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome Content: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "qid": 40, "docid": "shn7vx3d", "rank": 16, "score": 15.349900245666504}, {"content": "Title: Mutations on COVID-19 diagnostic targets Content: Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-2 has the most devastating mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been unfortunately used by countries around the world to diagnose COVID-19. Our findings explain what has seriously gone wrong with a specific diagnostic reagent made in China. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation ratio and mutation $h$-index of all SARS-CoV genes, indicating that the N gene is the most non-conservative gene in the SARS-CoV-2 genome. Our findings enable researchers to target the most conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, preventive vaccines, and therapeutic medicines.", "qid": 40, "docid": "8l7hrany", "rank": 17, "score": 15.340100288391113}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.", "qid": 40, "docid": "86byq11c", "rank": 18, "score": 15.271900177001953}, {"content": "Title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant Content: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "qid": 40, "docid": "16lkzgtq", "rank": 19, "score": 15.216899871826172}, {"content": "Title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant Content: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann\u2013Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2\u20135], otherwise they have a median of 1 mutation [range: 0\u20133] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "qid": 40, "docid": "ow2aijmj", "rank": 20, "score": 15.216898918151855}, {"content": "Title: MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences Content: With the continued spread of SARS-CoV-2 virus around the world, researchers often need to quickly identify novel mutations in newly sequenced SARS-CoV-2 genomes for studying the molecular evolution and epidemiology of the virus. We have developed a Python package, MicroGMT, which takes either raw sequence reads or assembled genome sequences as input and compares against database sequences to identify and characterize indels and point mutations. Although our default setting is optimized for SARS-CoV-2 virus, the package can be also applied to any other microbial genomes. The software is freely available at Github URL https://github.com/qunfengdong/MicroGMT.", "qid": 40, "docid": "ypwo98k7", "rank": 21, "score": 15.172900199890137}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 40, "docid": "bsypo08l", "rank": 22, "score": 15.1181001663208}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 40, "docid": "msggi1p2", "rank": 23, "score": 15.118099212646484}, {"content": "Title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity Content: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "qid": 40, "docid": "t8q99tlq", "rank": 24, "score": 15.019000053405762}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: BACKGROUND: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. METHODS: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. FINDING: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 40, "docid": "su5tlg3l", "rank": 25, "score": 15.018500328063965}, {"content": "Title: Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp Content: Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much delayed or even non-existent for the \u201cmutant\u201d (MT) strain that harbored both 14408 C>T and 23403 A>G mutations. Although these differences were not limited to a few hotspots, it is intriguing that the MDe increase is most evident in two critical genes, S and Orf1ab, which are also the genes that harbor the defining mutations of the MT genotype. The nature of these unexpected relationships warrant further research.", "qid": 40, "docid": "fglghjy6", "rank": 26, "score": 14.946100234985352}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 40, "docid": "tldg8c94", "rank": 27, "score": 14.946099281311035}, {"content": "Title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity Content: To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, the deconvolution of the entire set of intra-host variants reveals the existence of mutually exclusive viral mutational signatures, which prove that distinct hosts differently respond to SARS-CoV-2 infections. In particular, two signatures are likely ruled by APOBEC and Reactive Oxygen Species (ROS), which induce hypermutation in a significant number of samples, and appear to be affected by severe purifying selection. Conversely, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new viral genotypes and to an increase of overall genomic diversity. Finally, we demonstrate that a high number of variants are observed in samples associated to independent lineages, likely due to signature-related mutational hotspots or to positive selection.", "qid": 40, "docid": "7se14455", "rank": 28, "score": 14.945599555969238}, {"content": "Title: SARS-CoV-2 mutations altering regulatory properties: deciphering host\u2019s and virus\u2019s perspectives Content: Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host\u2019s and virus\u2019s perspective by analyzing the host miRNA binding and virus\u2019s internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.", "qid": 40, "docid": "6f1y5hhv", "rank": 29, "score": 14.906000137329102}, {"content": "Title: Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure Content: The rapid development of SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for the effective antivirals. SARS-CoV-2 is an RNA virus that has an inherent high mutation rate. These mutations drive viral evolution and genome variability, thereby, facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and \u2018Wuhan wet sea food market virus\u2019 sequence to identify, if any, variation between them. We report seven mutations observed in Indian SARS-CoV-2 isolates and three unique mutations that showed changes in the secondary structure of the RdRp protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that these mutations alter the stability of RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.", "qid": 40, "docid": "3pribklz", "rank": 30, "score": 14.829700469970703}, {"content": "Title: Stability of SARS-CoV-2 Phylogenies Content: The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse. Foreword We wish to thank all groups that responded rapidly by producing these invaluable and essential sequence data. Their contributions have enabled an unprecedented, lightning-fast process of scientific discovery---truly an incredible benefit for humanity and for the scientific community. We emphasize that most lab groups with whom we associate specific suspicious alleles are also those who have produced the most sequence data at a time when it was urgently needed. We commend their efforts. We have already contacted each group and many have updated their sequences. Our goal with this work is not to highlight potential errors, but to understand the impacts of these and other kinds of highly recurrent mutations so as to identify commonalities among the suspicious examples that can improve sequence quality and analysis going forward.", "qid": 40, "docid": "aqkpnz0o", "rank": 31, "score": 14.825799942016602}, {"content": "Title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum Content: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.", "qid": 40, "docid": "8871aifz", "rank": 32, "score": 14.670499801635742}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario Content: Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 40, "docid": "2nvk7glh", "rank": 33, "score": 14.638500213623047}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario. Content: Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 40, "docid": "bcx51aci", "rank": 34, "score": 14.63849925994873}, {"content": "Title: Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets Content: To identify features in the genome of the SARS-CoV-2 pathogen responsible for the COVID-19 pandemic that may contribute to its viral replication, host pathogenicity, and vulnerabilities, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes. Our analyses suggest the presence of unique sequence signatures in the 3\u2019-untranslated region (UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2, SARS-CoV, as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host microRNA-mediated interaction between the 3\u2019-UTR and human microRNA hsa-miR-1307-3p based on predicted, yet extensive, complementary base-pairings and similar interactions involving the Influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3\u2019-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection, and the exploitation of conserved features in the 3\u2019-UTR as therapeutic targets warrant further investigation.", "qid": 40, "docid": "gu3a677i", "rank": 35, "score": 14.529199600219727}, {"content": "Title: Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry Content: The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the angiotensin-converting enzyme-2 (ACE2) receptor and is cleaved by transmembrane protease serine 2 (TMPRSS2). However, whether S mutations affect SARS-CoV-2 infectivity remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural observations. Nevertheless, the D614G mutant remains susceptible to neutralization by antisera against prototypic viruses. Taken together, these data indicate that the D614G mutation enhances viral infectivity while maintaining neutralization susceptibility.", "qid": 40, "docid": "9m3lc4y8", "rank": 36, "score": 14.460200309753418}, {"content": "Title: Mega-phylogeny sheds light on SARS-CoV-2 spatial phylogenetic structure Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid spread on the virus evolution are under investigation. In this work, we analyzed ca. 9,000 SARS-CoV-2 genomes from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different genetic variants that are unevenly distributed on Earth. Furthermore, we demonstrate that SARS-CoV-2 phylogeny is spatially structured. We hypothesize this could be the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. In light of our results, we discuss how dispersal may constitute an opportunity for the virus to fix otherwise rare, and/or develop new, mutations. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote. Relevance A cluster of pneumonia cases of unknown etiology was reported in December 2019 in Wuhan, Hubei province, China. Since then, hundreds of thousands of people have died all around the planet. Quickly after the pandemic onset, metagenomic studies showed the causative agent, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonged to the Betacoronavirus genus, responsible for spillover events in 2002 and 2012 (severe acute respiratory syndrome and Middle East respiratory syndrome, respectively). The zoonotic origins of these viruses (possibly bats, camelids, pangolins and/or palm civets) have received much attention. However, other evolutionary aspects, such as spatial variation, have received comparatively little attention. This study shows that SARS-CoV-2 variants, which we call virotypes, are heterogeneously distributed on Earth and demonstrates that the virus phylogeny is geographically structured. We explain how this may be due to founder effects combined with high mutation rates.", "qid": 40, "docid": "3k5lmawz", "rank": 37, "score": 14.378999710083008}, {"content": "Title: Genomic, geographic and temporal distributions of SARS-CoV-2 mutations Content: The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.", "qid": 40, "docid": "1vhxcbx7", "rank": 38, "score": 14.358799934387207}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility. Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.", "qid": 40, "docid": "02cfyuf4", "rank": 39, "score": 14.342499732971191}, {"content": "Title: Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the \u201cconfined virus\u201d? Content: The Coronavirus disease 19 (COVID-19) pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome. Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2. These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely.", "qid": 40, "docid": "xbn5ov9s", "rank": 40, "score": 14.327400207519531}, {"content": "Title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism Content: As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.", "qid": 40, "docid": "8ow952d8", "rank": 41, "score": 14.32390022277832}, {"content": "Title: Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing Content: Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.", "qid": 40, "docid": "6n4updwi", "rank": 42, "score": 14.199600219726562}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird\u2019s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.", "qid": 40, "docid": "6dsx7pey", "rank": 43, "score": 14.190400123596191}, {"content": "Title: A comparative analysis for SARS-CoV-2 Content: COVID-19 has affected the world tremendously. It is critical that biological experiments and clinical designs are informed by computational approaches for time- and cost-effective solutions. Comparative analyses particularly can play a key role to reveal structural changes in proteins due to mutations, which can lead to behavioural changes, such as the increased binding of the SARS-CoV-2 surface glycoprotein to human ACE2 receptors. The aim of this report is to provide an easy to follow tutorial for biologists and others without delving into different bioinformatics tools. More complex analyses such as the use of large-scale computational methods can then be utilised. Starting with a SARS-CoV-2 genome sequence, the report shows visualising DNA sequence features, deriving amino acid sequences, and aligning different genomes to analyse mutations and differences. The report provides further insights into how the SARS-CoV-2 surface glycoprotein mutated for higher binding affinity to human ACE2 receptors, compared to the SARS-CoV protein, by integrating existing 3D protein models.", "qid": 40, "docid": "nuqx3tv6", "rank": 44, "score": 14.187800407409668}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads. Whole-genome sequencing data offers a wide range of opportunities to study mutation dynamics. The advantage of an increasing amount of whole-genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity, and to investigate the implications of those mutations in protein stability and viral transmission. We have identified frequently mutated residues by aligning ~660 SARS-CoV-2 genomes and validated in 10,000 datasets available in GISAID Nextstrain. We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins. Among the 11 genes, surface glycoprotein, nucleocapsid, ORF1ab, and ORF8 showed frequent mutations, while envelop, membrane, ORF6, ORF7a and ORF7b showed conservation in terms of amino acid substitutions. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Some of the mutations across different proteins showed co-occurrences, suggesting their structural and/or functional interaction among different SARS-COV-2 proteins, and their involvement in adaptability and viral transmission. Analysis of protein structure stability of surface glycoprotein mutants indicated the viability of specific variants and are more prone to be temporally and spatially distributed across the globe. A similar empirical analysis of other proteins indicated the existence of important functional implications of several variants. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing, and containment of the disease.", "qid": 40, "docid": "q86nga34", "rank": 45, "score": 14.175000190734863}, {"content": "Title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation.", "qid": 40, "docid": "4e3cn50u", "rank": 46, "score": 14.171799659729004}, {"content": "Title: Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting. Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "qid": 40, "docid": "8cex7qi4", "rank": 47, "score": 14.171798706054688}, {"content": "Title: Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "qid": 40, "docid": "eri92ki6", "rank": 48, "score": 14.171797752380371}, {"content": "Title: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts Content: The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "qid": 40, "docid": "k4l759k2", "rank": 49, "score": 14.125}, {"content": "Title: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts. Content: The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "qid": 40, "docid": "ox7xetlq", "rank": 50, "score": 14.124999046325684}, {"content": "Title: COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data Content: COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.", "qid": 40, "docid": "r0gr0bhl", "rank": 51, "score": 14.109800338745117}, {"content": "Title: Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus. Content: BACKGROUND SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper. METHODS Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods. RESULTS There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals. CONCLUSION The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.", "qid": 40, "docid": "3n37dlt4", "rank": 52, "score": 14.06350040435791}, {"content": "Title: Structural and Functional Implications of Spike Protein Mutational Landscape in SARS-CoV-2 Content: SARS-CoV-2, the causative agent of COVID-19 pandemic, is an RNA virus prone to mutations. Interaction of SARS-CoV-2 Spike (S) protein with the host cell receptor, Angiotensin-I Converting Enzyme 2 (ACE2) is pivotal for attachment and entry of the virus. Yet, natural mutations acquired on S protein during the pandemic and their impact on viral infectivity, transmission dynamics and disease pathogenesis remains poorly understood. Here, we analysed 2952 SARS-CoV-2 genomes across the globe, and identified a total of 1815 non-synonymous mutations in the S-protein that fall into 54 different types. We observed that six of these distinct mutations were located in the Receptor Binding Domain (RBD) region that directly engages host ACE2. Molecular phylogenetic analysis revealed that these RBD mutations cluster into distinct phyletic clades among global subtypes of SARS-CoV-2 implying possible emergence of novel sublineages of the strain. Structure-guided homology modelling and docking analysis predicted key molecular rearrangements in the ACE2 binding interface of RBD mutants that could result in altered virus-host interactions. We propose that our findings could be significant in understanding disease dynamics and in developing vaccines, antibodies and therapeutics for COVID-19. Importance COVID-19 pandemic shows considerable variations in disease transmission and pathogenesis globally, yet reasons remain unknown. Our study identifies key S-protein mutations prevailing in SARS-CoV-2 strain that could alter viral attachment and infectivity. We propose that the interplay of these mutations could be one of the factors driving global variations in COVID-19 spread. In addition, the mutations identified in this study could be an important indicator in predicting efficacies of vaccines, antibodies and therapeutics that target SARS-CoV-2 RBD-ACE2 interface.", "qid": 40, "docid": "40xsypzt", "rank": 53, "score": 14.041500091552734}, {"content": "Title: High Throughput Designing and Mutational Mapping of RBD-ACE2 Interface Guide Non-Conventional Therapeutic Strategies for COVID-19 Content: Considering the current status of the SARS-CoV-2 pandemic, sequence variations and possibly structural changes in the rapidly evolving SARS-CoV-2 is highly expected in the coming months. The SARS-CoV-2 spike (S) protein is responsible for mediating viral attachment and fusion with cell membranes. Mutations in the receptor-binding domain (RBD) of the S-protein occur at the most variable part of the SARS-CoV-2 genome, and specific sites of S-protein have undergone positive selection impacting the viral pathogenicity. In the present work, we used high-throughput computation to design 100,000 mutants in RBD interfacial residues and identify novel affinity-enhancing and affinity-weakening mutations. Our data suggest that SARS-CoV-2 can establish a higher rate of infectivity and pathogenesis when it acquires combinatorial mutations at the interfacial residues in RBD. Mapping of the mutational landscape of the interaction site suggests that a few of these residues are the hot-spot residues with a very high tendency to undergo positive selection. Knowledge of the affinity-enhancing mutations may guide the identification of potential cold-spots for this mutation as targets for developing a possible therapeutic strategy instead of hot-spots, and vice versa. Understanding of the molecular interactions between the virus and host protein presents a detailed systems view of viral infection mechanisms. The applications of the present research can be explored in multiple antiviral strategies, including monoclonal antibody therapy, vaccine design, and importantly in understanding the clinical pathogenesis of the virus itself. Our work presents research directions for the exploitation of non-conventional solutions for COVID-19.", "qid": 40, "docid": "l7471mik", "rank": 54, "score": 14.002799987792969}, {"content": "Title: The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019 Content: The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.", "qid": 40, "docid": "5qn5h7p5", "rank": 55, "score": 13.995100021362305}, {"content": "Title: Patient-derived mutations impact pathogenicity of SARS-CoV-2 Content: The sudden outbreak of the severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. Here we report functional characterizations of 11 patient-derived viral isolates, all of which have at least one mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. We observed intrapersonal variation and 6 different mutations in the spike glycoprotein (S protein), including 2 different SNVs that led to the same missense mutation. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.", "qid": 40, "docid": "3eu9umx5", "rank": 56, "score": 13.970499992370605}, {"content": "Title: Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003 Content: BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 \u00d7 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' \u2013 most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.", "qid": 40, "docid": "0gmtnkbh", "rank": 57, "score": 13.959600448608398}, {"content": "Title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Content: The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.", "qid": 40, "docid": "fw4pmaoc", "rank": 58, "score": 13.943400382995605}, {"content": "Title: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 Content: Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of \u201cgenome-type clusters\u201d and adaptive selection of \u201cL\u201d type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the \u201cmajor group\u201d (52.2%) and the \u201cminor group\u201d (30.4%), harboring four and five co-existing mutations, respectively. The \u201cmajor group\u201d mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.", "qid": 40, "docid": "915srotp", "rank": 59, "score": 13.93529987335205}, {"content": "Title: Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China Content: A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of husband and wife without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of S genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37x10-3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.", "qid": 40, "docid": "m9k6upe4", "rank": 60, "score": 13.904600143432617}, {"content": "Title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates Content: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL(pro)) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL(pro) enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.", "qid": 40, "docid": "d25qfq0f", "rank": 61, "score": 13.870100021362305}, {"content": "Title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates Content: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.", "qid": 40, "docid": "qc5bhxgj", "rank": 62, "score": 13.870099067687988}, {"content": "Title: The Novel Coronavirus SARS\u2010CoV\u20102: From a Zoonotic Infection to Coronavirus Disease\u201019 (COVID19) Content: OBJECTIVE: The novel coronavirus, SARS\u2010CoV\u20102 is an international public health emergency. Until now, the intermediate host and mechanisms of interspecies jump of this virus are unknown. METHODS: Phylogenetic analysis of all available bat coronavirus (CoV) complete genomes was performed in order to analyze the relationships between bat CoV and SARS\u2010CoV\u20102. In order to suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals which were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions which may have permitted the adaptation of SARS\u2010CoV\u20102 to the human host. RESULTS: The phylogenetic analysis demonstrated that SARS\u2010CoV\u20102 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS\u2010CoV\u20102, bat RaTG13 and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS\u2010CoV\u20102 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS\u2010CoV\u20102 tropism to human cells. CONCLUSIONS: Our analysis shows the tight relationship between SARS\u2010CoV\u20102 and bat SARS\u2010like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function. This article is protected by copyright. All rights reserved.", "qid": 40, "docid": "4ze0mfxp", "rank": 63, "score": 13.853500366210938}, {"content": "Title: Anti-frameshifting ligand active against SARS coronavirus-2 is resistant to natural mutations of the frameshift-stimulatory pseudoknot Content: The coronavirus SARS-CoV-2 causing the COVID-19 pandemic uses \u22121 programmed ribosomal frameshifting (\u22121 PRF) to control the expression levels of key viral proteins. Because modulating \u22121 PRF can attenuate viral propagation, ligands binding to the viral RNA pseudoknot that stimulates \u22121 PRF may prove useful as therapeutics. Mutations in the pseudoknot have been observed over the course of the pandemic, but how they affect \u22121 PRF and the activity of inhibitors is unknown. Cataloguing natural mutations in all parts of the SARS-CoV-2 pseudoknot, we studied a panel of 6 mutations in key structural regions. Most mutations left the \u22121 PRF efficiency unchanged, even when base-pairing was disrupted, but one led to a remarkable three-fold decrease, suggesting that SARS-CoV-2 propagation may be less sensitive to modulation of \u22121 PRF efficiency than some other viruses. Examining the effects of one of the few small-molecule ligands known to suppress \u22121 PRF significantly in SARS-CoV, we found that it did so by similar amounts in all SARS-CoV-2 mutants tested, regardless of the basal \u22121 PRF efficiency, indicating that the activity of anti-frameshifting ligands can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of \u22121 PRF.", "qid": 40, "docid": "iinpkixn", "rank": 64, "score": 13.819999694824219}, {"content": "Title: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13 Content: The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3\u2019-to-5\u2019 exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.", "qid": 40, "docid": "3h1o0oz3", "rank": 65, "score": 13.804699897766113}, {"content": "Title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "qid": 40, "docid": "fujejfwb", "rank": 66, "score": 13.796099662780762}, {"content": "Title: SARS-CoV-2 spread across the Colombian-Venezuelan border Content: Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuelan ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region. We sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages Pangolin tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference. We found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. An additional three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome. Conclusions: Genomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region.", "qid": 40, "docid": "umoowoa2", "rank": 67, "score": 13.793299674987793}, {"content": "Title: [Follow up study on viruses associated with SARS among the SARS patients]. Content: BACKGROUND To study the existence status of the SARS-CoV, retrovirus, and the poliovirus in the bodies of the patients with SARS and the possible relationship between the three viruses and SARS. METHODS The clinical specimens of the nasopharyngeal swabs, sputum (or saliva), urine, fecal specimens were collected on three consecutive days from 8 patients with SARS 2 years after the recovery from SARS. SARS-CoV, reovirus and poliovirus RNA was detected by using reverse transcription (RT)-PCR; IgG antibody to the poliovirus type 1 and 3 and the antibody to SARS-CoV were determined using enzyme linked immunosorbent assay (ELISA). RESULTS All the specimens were negative for SARS-CoV and reovirus by RT-PCR, but the fecal specimens from 4 persons were positive for poliovirus. The sequences of these poliovirus were highly homologous to that of human poliovirus type 1 strain sabin 1 genome at nucleotide level, but back mutations have occurred in the primary attenuating mutation sites at nucleotide position 480 (G --> A) in the 5' UTR and the nucleotide position 2795 (A --> G). No SARS-CoV, reovirus, and poliovirus were found in the normal controls. Three serum specimens were positive for the antibody to SARS-CoV. The IgG antibody to poliovirus were detected in 4 SARS patients and 23 healthy persons. No positive results for antibody to SARS-CoV were detected in the 25 healthy persons. CONCLUSION The positive rate of the poliovirus antibody in the serum of SARS patients 2 years after recovery was significantly different from that of the normal controls, and the positive rate of poliovirus in the fecal specimens was still very high, and more importantly back mutations have occurred in the attenuating mutation sites at nucleotide position which plays an important role in the poliomyelitis.", "qid": 40, "docid": "trw1erpj", "rank": 68, "score": 13.748200416564941}, {"content": "Title: Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in Spike Glycoprotein Content: SARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isn\u2019t detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in the spike gene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.", "qid": 40, "docid": "jj0n81s9", "rank": 69, "score": 13.72089958190918}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 40, "docid": "mp3196kj", "rank": 70, "score": 13.693699836730957}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 40, "docid": "vjfquvlu", "rank": 71, "score": 13.69369888305664}, {"content": "Title: Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding Content: The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor, and is a major determinant of host range and a dominant target of neutralizing antibodies. Here we experimentally measure how all amino-acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD\u2019s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.", "qid": 40, "docid": "4xaounho", "rank": 72, "score": 13.676400184631348}, {"content": "Title: D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly Content: The iconic \u201cred crown\u201d of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made of its spike (S) glycoprotein. The S protein is the Trojan horse of coronaviruses, mediating their entry into the host cells. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On April 21st, the GISAID resource had collected 10,823 SARS-CoV-2 genomic sequences. We extracted from them all the complete S protein sequences and identified point mutations thereof. Six mutations were located on a 14-residue segment (929-943) in the \u201cfusion core\u201d of the heptad repeat 1 (HR1). Our modeling in the pre- and post-fusion S protein conformations revealed, for three of them, the loss of interactions stabilizing the post-fusion assembly. On May 29th, the SARS-CoV-2 genomic sequences in GISAID were 34,805. An analysis of the occurrences of the HR1 mutations in this updated dataset revealed a significant increase for the S929I and S939F mutations and a dramatic increase for the D936Y mutation, which was particularly widespread in Sweden and Wales/England. We notice that this is also the mutation causing the loss of a strong inter-monomer interaction, the D936-R1185 salt bridge, thus clearly weakening the post-fusion assembly.", "qid": 40, "docid": "iihgc5nr", "rank": 73, "score": 13.629199981689453}, {"content": "Title: Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. Content: SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.", "qid": 40, "docid": "pljeao4b", "rank": 74, "score": 13.627799987792969}, {"content": "Title: Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses \u2013 causes and consequences for their short and long evolutionary trajectories Content: The pandemic of SARS coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a dataset of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean 5.5-9.5 nucleotide differences from each other, commensurate with a mid-range coronavirus substitution rate of 3\u00d710\u22124 substitutions/site/year. Almost half of sequence changes were C->U transitions with an 8-fold base frequency normalised directional asymmetry between C->U and U->C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV and MERS-CoV) and to a decreasing degree in other human coronaviruses (HCoV-NL63, -OC43, -229E and -HKU1) proportionate to their increasing divergence. C->U transitions underpinned almost half of the amino acid differences between SARS-CoV-2 variants, and occurred preferentially in both 5\u2019U/A and 3\u2019U/A flanking sequence contexts comparable to favoured motifs of human APOBEC3 proteins. Marked base asymmetries observed in non-pandemic human coronaviruses (U>>A>G>>C) and low G+C contents may represent long term effects of prolonged C->U hypermutation in their hosts. Importance The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short and long term evolution. Repeated cycles of mutation and reversion in favoured mutational hotspots and the widespread occurrence of amino acid changes with no adaptive value for the virus represents a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks that are typically used in molecular epidemiology investigations.", "qid": 40, "docid": "rcv8sh22", "rank": 75, "score": 13.62339973449707}, {"content": "Title: Tracing two causative SNPs reveals SARS-CoV-2 transmission in North America population Content: During the COVID-19 pandemic, precisely tracing the route of the SARS-CoV-2 transmission in human population remains challenging. Because this RNA virus can mutate massively without a specifically tracing maker. Herein, using a geographic stratified genome-wide association study (GWAS) of 2599 full-genome sequences, we identified that two SNPs (i.e., 1059.C>T and 25563.G>T) of linkage disequilibrium were presented in approximately half of North America SARS-CoV-2 population (p = 2.44 x 10\u2212212 and p = 2.98 x 10\u2212261), resulting two missense mutations (i.e., Thr 265 Ile and Gln 57 His) in ORF1ab and ORF3a, respectively. Interestingly, these two SNPs exclusively occurred in the North America dominated clade 1, accumulated during mid to late March, 2020. We did not find any of these two SNPs by retrospectively tracing the two SNPs in bat and pangolin related SARS-CoV-2 and human SARS-CoV-2 from the first epicenter Wuhan or other regions of China mainland. This suggested that the SARS-CoV-2 population of Chinese mainland were different from the prevalent strains of North America. Time-dependently, we found that these two SNPs first occurred in Europe SARS-CoV-2 (26-Feb-2020) which was 3 days early than the occurring date of North America isolates and 17 days early for Asia isolates (Taiwan China dominated). Collectively, this population genetic analysis highlights a well-confidential transmission route of the North America isolates and the two SNPs we newly identified are possibly novel diagnosable or druggable targets for surveillance and treatment.", "qid": 40, "docid": "q38epuxa", "rank": 76, "score": 13.590299606323242}, {"content": "Title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis Content: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes", "qid": 40, "docid": "tjmx6msm", "rank": 77, "score": 13.589900016784668}, {"content": "Title: Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy Content: A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (\u00e2\u0088\u00bc82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (Mpro) or 3-chymotrypsin-like cysteine protease (3CLpro), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, Mpro is highly conserved among various CoVs, and a mutation in Mpro is often lethal to the virus. Thus, drugs targeting the Mpro enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV Mpro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV Mpro on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.", "qid": 40, "docid": "8bzu2gn0", "rank": 78, "score": 13.533900260925293}, {"content": "Title: Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified the H49Y amino acid change in the Spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 40, "docid": "1yf5y06o", "rank": 79, "score": 13.530200004577637}, {"content": "Title: Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico. Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified the H49Y amino acid change in the Spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 40, "docid": "i29eufyo", "rank": 80, "score": 13.53019905090332}, {"content": "Title: Population genomics insights into the recent evolution of SARS-CoV-2 Content: The current coronavirus disease 2019 (COVID-19) pandemic is caused by the SARS-CoV-2 virus and is still spreading rapidly worldwide. Full-genome-sequence computational analysis of the SARS-CoV-2 genome will allow us to understand the recent evolutionary events and adaptability mechanisms more accurately, as there is still neither effective therapeutic nor prophylactic strategy. In this study, we used population genetics analysis to infer the mutation rate and plausible recombination events that may have contributed to the evolution of the SARS-CoV-2 virus. Furthermore, we localized targets of recent and strong positive selection. The genomic regions that appear to be under positive selection are largely co-localized with regions in which recombination from non-human hosts appeared to have taken place in the past. Our results suggest that the pangolin coronavirus genome may have contributed to the SARS-CoV-2 genome by recombination with the bat coronavirus genome. However, we find evidence for additional recombination events that involve coronavirus genomes from other hosts, i.e., Hedgehog and Sparrow. Even though recombination events within human hosts cannot be directly assessed, due to the high similarity of SARS-CoV-2 genomes, we infer that recombinations may have recently occurred within human hosts using a linkage disequilibrium analysis. In addition, we employed an Approximate Bayesian Computation approach to estimate the parameters of a demographic scenario involving an exponential growth of the size of the SARS-CoV-2 populations that have infected European, Asian and Northern American cohorts, and we demonstrated that a rapid exponential growth in population size can support the observed polymorphism patterns in SARS-CoV-2 genomes.", "qid": 40, "docid": "1fxrmuzl", "rank": 81, "score": 13.528499603271484}, {"content": "Title: Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses Content: Within four months of the ongoing COVID-19 pandemic caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in the ORF1 of the virus isolated from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of nonsynonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerated sites towards uracil residues is seen in ORF1 of all the studied coronaviruses. A more substantial mutational U pressure is observed in ORF1a than in ORF1b owing to the translation of ORF1ab via programmed ribosomal frameshifting. Unlike other nucleotide mutations, mutational U pressure caused by cytosine deamination, mostly occurring in the RNA-plus strand, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the direction of mutational pressure during translation of viral RNA-plus strands has implications for vaccine and nucleoside analogue development for treating covid-19 and other coronavirus infections.", "qid": 40, "docid": "ug8xh52p", "rank": 82, "score": 13.525300025939941}, {"content": "Title: Genome-wide analysis of Indian SARS-CoV-2 genomes for the identification of genetic mutation and SNP Content: The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is build to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population.", "qid": 40, "docid": "lt0uo7q3", "rank": 83, "score": 13.505599975585938}, {"content": "Title: Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission Content: The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.", "qid": 40, "docid": "2nijfrn5", "rank": 84, "score": 13.496999740600586}, {"content": "Title: coronapp: A Web Application to Annotate and Monitor SARS-CoV-2 Mutations Content: The avalanche of genomic data generated from the SARS-CoV-2 virus requires the development of tools to detect and monitor its mutations across the World. Here, we present a webtool, coronapp, dedicated to easily processing user-provided SARS-CoV-2 genomic sequences, in order to detect and annotate protein-changing mutations. This results in an up-to-date status of SARS-CoV-2 mutations, both worldwide and in user-selected countries. The tool allows users to highlight and prioritize the most frequent mutations in specific protein regions, and to monitor their frequency in the population over time. The tool is available at http://giorgilab.dyndns.org/coronapp/ and the full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronapp", "qid": 40, "docid": "pfhfmck1", "rank": 85, "score": 13.4621000289917}, {"content": "Title: Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus Content: The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.", "qid": 40, "docid": "c4q5gtw2", "rank": 86, "score": 13.39490032196045}, {"content": "Title: Genotyping coronavirus SARS-CoV-2: methods and implications Content: The emerging global infectious COVID-19 coronavirus disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "qid": 40, "docid": "ulygq434", "rank": 87, "score": 13.38479995727539}, {"content": "Title: RdRp mutations are associated with SARS-CoV-2 genome evolution Content: COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.", "qid": 40, "docid": "i09lh5i6", "rank": 88, "score": 13.360600471496582}, {"content": "Title: Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy Content: [Image: see text] A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (\u223c82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M(pro)) or 3-chymotrypsin-like cysteine protease (3CL(pro)), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M(pro) is highly conserved among various CoVs, and a mutation in M(pro) is often lethal to the virus. Thus, drugs targeting the M(pro) enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M(pro) represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV M(pro) on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.", "qid": 40, "docid": "q044i7ym", "rank": 89, "score": 13.353099822998047}, {"content": "Title: Genotyping coronavirus SARS-CoV-2: Methods and implications Content: Abstract The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "qid": 40, "docid": "jujrazsr", "rank": 90, "score": 13.324999809265137}, {"content": "Title: Genotyping coronavirus SARS-CoV-2: methods and implications Content: The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "qid": 40, "docid": "leyqhma0", "rank": 91, "score": 13.32499885559082}, {"content": "Title: Time-series analyses of directional sequence changes in SARS-CoV-2 genomes and an efficient search method for advantageous mutations for growth in human cells Content: We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.", "qid": 40, "docid": "0d9hzmyk", "rank": 92, "score": 13.298299789428711}, {"content": "Title: Failure of the cobas(R) SARS-CoV-2 (Roche) E-gene assay is associated with a C-to-T transition at position 26340 of the SARS-CoV-2 genome Content: Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of RT-PCR tests have been developed to identify SARS-CoV-2, targeting multiple regions in the viral genome. In comparison to other RNA viruses the mutation rate of SARS-CoV-2 is moderate, however given the large number of transmission chains it is prudent to monitor circulating viruses for mutations that might compromise these tests. Here we report the identification of a C-to-T transition at position 26340 of the SARS-CoV-2 genome which is associated with failure of the cobas(R) SARS-CoV-2 E-gene assay. This variant was detected in four health care workers from the same team. Whole genome sequencing of SARS-CoV-2 showed all four to carry genetically identical viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently on three occasions. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect the RT-PCRs used in diagnostics. Additionally, it argues that two regions in the SARS-CoV-2 should be targeted in RT-PCRs to avoid false negatives.", "qid": 40, "docid": "vd62r8qu", "rank": 93, "score": 13.285599708557129}, {"content": "Title: Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic Content: Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5'UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10 percent of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50 percent of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.", "qid": 40, "docid": "h3ftgzqz", "rank": 94, "score": 13.280599594116211}, {"content": "Title: Genomic analysis of early SARS-CoV-2 strains introduced in Mexico Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 40, "docid": "le0ftbps", "rank": 95, "score": 13.242400169372559}, {"content": "Title: Complexity in SARS-CoV-2 genome data: Price theory of mutant isolates Content: SARS-CoV-2 is a highly virulent and deadly RNA virus causing the Covid-19 pandemic and several deaths across the world. The pandemic is so fast that any concrete theory of sudden widespread of this disease is still not known. In this work, we studied and analyzed a large number of publicly available SARS-CoV-2 genomes across the world using the multifractal approach. The mutation events in the isolates obey the Markov process and exhibit very high mutational rates, which occur in six specific genes and highest in orf1ab gene, leading to virulent nature. f (\u03b1) analysis indicated that the isolates are highly asymmetric (left-skewed), revealing the richness of complexity and dominance by large fluctuations in genome structure organization. The values of Hq and Dq are found to be significantly large, showing heterogeneous genome structure self-organization, strong positive correlation in organizing the isolates, and quite sensitive to fluctuations in and around it. We then present multiple-isolates hosts-virus interaction models, and derived Price equation for the model. The phase plane analysis of the model showed asymptotic stability type bifurcation. The competition among the mutant isolates drives the trade-off of the dominant mutant isolates, otherwise confined to the present hosts.", "qid": 40, "docid": "s0coelac", "rank": 96, "score": 13.236000061035156}, {"content": "Title: Multiple assays in a real-time RT-PCR SARS-CoV-2 panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak Content: OBJECTIVES: In this study, five SARS-CoV-2 PCR assay panels were evaluated against the accumulated genetic variability of the virus to assess the effect on sensitivity of the individual assays. DESIGN OR METHODS: As of week 21, 2020, the complete set of available SARS-CoV-2 genomes from GISAID and GenBank databases were used in this study. SARS-CoV-2 primer sequences from publicly available panels (WHO, CDC, NMDC, and HKU) and QIAstat-Dx were included in the alignment, and accumulated genetic variability affecting any oligonucleotide annealing was annotated. RESULTS: A total of 11,627 (34.38%) genomes included single mutations affecting annealing of any PCR assay. Variations in 8,773 (25.94%) genomes were considered as high risk, whereas additional 2,854 (8.43%) genomes presented low frequent single mutations and were predicted to yield no impact on sensitivity. In case of the QIAstat-Dx SARS-CoV-2 Panel, 99.11% of the genomes matched with a 100% coverage all oligonucleotides, and critical variations were tested in vitro corroborating no loss of sensitivity. CONCLUSIONS: This analysis stresses the importance of targeting more than one region in the viral genome for SARS-CoV-2 detection to mitigate the risk of loss of sensitivity due to the unknown mutation rate during this SARS-CoV-2 outbreak.", "qid": 40, "docid": "ydfe06ua", "rank": 97, "score": 13.218000411987305}, {"content": "Title: Large-Scale Phylogenetic Analysis of Emerging Infectious Diseases Content: Microorganisms that cause infectious diseases present critical issues of national security, public health, and economic welfare. For example, in recent years, highly pathogenic strains of avian influenza have emerged in Asia, spread through Eastern Europe, and threaten to become pandemic. As demonstrated by the coordinated response to Severe Acute Respiratory Syndrome (SARS) and influenza, agents of infectious disease are being addressed via large-scale genomic sequencing. The goal of genomic sequencing projects are to rapidly put large amounts of data in the public domain to accelerate research on disease surveillance, treatment, and prevention. However, our ability to derive information from large comparative genomic datasets lags far behind acquisition. Here we review the computational challenges of comparative genomic analyses, specifically sequence alignment and reconstruction of phylogenetic trees. We present novel analytical results on two important infectious diseases, Severe Acute Respiratory Syndrome (SARS) and influenza. SARS and influenza have similarities and important differences both as biological and comparative genomic analysis problems. Influenza viruses (Orthymxyoviridae) are RNA based. Current evidence indicates that influenza viruses originate in aquatic birds from wild populations. Influenza has been studied for decades via well-coordinated international efforts. These efforts center on surveillance via antibody characterization of the hemagglutinin (HA) and neuraminidase (N) proteins of the circulating strains to inform vaccine design. However, we still do not have a clear understanding of (1) various transmission pathways such as the role of intermediate hosts like swine and domestic birds and (2) the key mutation and genomic recombination events that underlie periodic pandemics of influenza. In the past 30 years, sequence data from HA and N loci has become an important data type. In the past year, full genomic data has become prominent. These data present exciting opportunities to address unanswered questions in influenza pandemics. SARS is caused by a previously unrecognized lineage of coronavirus, SARS-CoV, which like influenza has an RNA based genome. Although SARS-CoV is widely believed to have originated in animals, there remains disagreement over the candidate animal source that lead to the original outbreak of SARS. In contrast to the long history of the study of influenza, SARS was only recognized in late 2002 and the virus that causes SARS has been documented primarily by genomic sequencing. In the past, most studies of influenza were performed on a limited number of isolates and genes suited to a particular problem. Major goals in science today are to understand emerging diseases in broad geographic, environmental, societal, biological, and genomic contexts. Synthesizing diverse information brought together by various researchers is important to find out what can be done to prevent future outbreaks [JON03]. Thus comprehensive means to organize and analyze large amounts of diverse information are critical. For example, the relationships of isolates and patterns of genomic change observed in large datasets might not be consistent with hypotheses formed on partial data. Moreover when researchers rely on partial datasets, they restrict the range of possible discoveries. Phylogenetics is well suited to the complex task of understanding emerging infectious disease. Phylogenetic analyses can test many hypotheses by comparing diverse isolates collected from various hosts, environments, and points in time and organizing these data into various evolutionary scenarios. The products of a phylogenetic analysis are a graphical tree of ancestor\u2013descendent relationships and an inferred summary of mutations, recombination events, host shifts, geographic, and temporal spread of the viruses. However, this synthesis comes at a price. The cost of computation of phylogenetic analysis expands combinatorially as the number of isolates considered increases. Thus, large datasets like those currently produced are commonly considered intractable. We address this problem with synergistic development of heuristics tree search strategies and parallel computing.", "qid": 40, "docid": "cndb031c", "rank": 98, "score": 13.187600135803223}, {"content": "Title: Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin Content: The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.", "qid": 40, "docid": "hib30ct6", "rank": 99, "score": 13.169699668884277}, {"content": "Title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.", "qid": 40, "docid": "o9oxchq6", "rank": 100, "score": 13.110199928283691}]}
{"query": "What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population?", "hits": [{"content": "Title: The impact of COVID-19 on African American communities in the United States Content: IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.", "qid": 41, "docid": "80w0wu9e", "rank": 1, "score": 16.93869972229004}, {"content": "Title: Racial segregation, testing sites access, and COVID-19 incidence rate in Massachusetts, USA Content: The U.S. has merely 4% of the world population but 25% of the world's COVID-19 cases. Massachusetts has been in the leading position of total cases since the outbreak in the U.S. Racial residential segregation is a fundamental cause of racial disparities in health. Moreover, disparities of access to health care have a large impact on COVID-19 cases. Thus, this study estimates racial segregation and disparities in testing sites access and employs economic, demographic, and transportation variables at the city/town level in Massachusetts. Spatial regression models are applied to evaluate the relationships between COVID-19 incidence rate and related variables. This is the first study to apply spatial analysis methods across neighborhoods in the U.S. to examine the COVID-19 incidence rate. The findings are: 1) residential segregations of Hispanic and Non-Hispanic Black/African Americans have a significantly positive association with COVID-19 incidence rate, indicating the higher susceptibility of COIVD-19 infections among minority; 2) The Black has the shortest drive time to testing sites, followed by Hispanic, Asian, and Whites. The drive time to testing sites is significantly negatively associated with the COVID-19 incidence rate, implying the importance of testing location being accessed by all populations; 3) Poverty rate and road density are significant explanatory variables. Importantly, overcrowding represented by more than one person per room is a significant variable found to be positively associated with COVID-19 incidence rate, suggesting the effectiveness of social distancing for reducing infection; 4) Different from previous studies, elderly population rate is not statistically significant with incidence rate because the elderly population in Massachusetts is less distributed in the hot spot regions of COVID-19 infections. The findings in this study provide useful insights for policymakers to propose new strategies to contain the COVID-19 transmissions in Massachusetts.", "qid": 41, "docid": "gxjsv896", "rank": 2, "score": 15.091699600219727}, {"content": "Title: Racial and Ethnic Disparities in SARS-CoV-2 Pandemic: Analysis of a COVID-19 Observational Registry for a Diverse U.S. Metropolitan Population Content: Importance: Despite emerging reports of poor COVID-19 outcomes among African Americans, data on race and ethnic susceptibility to SARS-CoV-2 infection are limited. Objective: To determine socio-demographic factors associated with higher likelihood of SARS-CoV-2 infection. To explore mediating pathways for race disparities in the SARS-CoV-2 pandemic. Design: Cross sectional analysis of COVID-19 Surveillance and Outcomes Registry (CURATOR). Multivariable logistic regression models were fitted to provide likelihood estimates (adjusted Odds Ratios: aOR, 95% confidence intervals: CI) of positive SARS-CoV-2 test. Structural Equation Modeling (SEM) framework was utilized to explore three mediation pathways (low income, high population density, high comorbidity burden) for association between African American race and SARS-CoV-2 infection. Setting: A large healthcare system comprising of one central tertiary care, seven large community hospitals and an expansive ambulatory and emergency care network in the Greater Houston area. Participants: Individuals of all ages, races, ethnicities and sex tested for SARS-CoV-2. Exposure: Socio-demographic (age, sex, race, ethnicity, household income, residence population density) and comorbidity (hypertension, diabetes, obesity, cardiac disease) factors. Main Outcome: Positive reverse transcriptase polymerized chain reaction test for SARS-CoV-2. Results: Among 4,513 tested individuals, 754 (16.7%) tested positive. Overall mean (SD) age was 50.6 (18.9) years, 62% females and 26% were African American. African American race was associated with higher comorbidity burden, lower socio-economic status, and higher population density residence. In the fully adjusted model, African American race (vs. White; aOR, CI: 1.84, 1.49-2.27) and Hispanic ethnicity (vs. non-Hispanic; aOR, CI: 1.70, 1.35-2.14) had a higher likelihood of infection. Older individuals and males were also at a higher risk of SARS-CoV-2 infection. The SEM framework demonstrated a statistically significant (p = 0.008) indirect effect of African American race on SARS-CoV-2 infection mediated via a pathway that included residence in densely populated zip code. Conclusions and Relevance: There is strong evidence of race and ethnic disparities in the SARS-CoV-2 pandemic potentially mediated through unique social determinants of health.", "qid": 41, "docid": "guvkeog0", "rank": 3, "score": 14.458399772644043}, {"content": "Title: Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett's esophagus: results from the U.S. RFA Registry. Content: BACKGROUND Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). OBJECTIVE We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. DESIGN The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. PATIENTS Patients enrolled with BE. INTERVENTIONS RFA. MAIN OUTCOME MEASUREMENTS We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. RESULTS Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. LIMITATIONS Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. CONCLUSION In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race.", "qid": 41, "docid": "3rhm9lb9", "rank": 4, "score": 14.432100296020508}, {"content": "Title: How bad is it? Suicidality in the middle of the COVID\u201019 pandemic Content: OBJECTIVE: The current paper examines the intersection between social vulnerability, individual risk, and social/psychological resources with adult suicidality during the COVID\u201019 pandemic. METHOD: Data come from a national sample (n = 10,368) of U.S. adults. Using an online platform, information was gathered during the third week of March 2020, and post\u2010stratification weighted to proportionally represent the U.S. population in terms of age, gender, race/ethnicity, income, and geography. RESULTS: Nearly 15 percent of sampled respondents were categorized as high risk, scoring 7+ on the Suicide Behaviors Questionnaire\u2010Revised (SBQ\u2010R). This level of risk varied across social vulnerability groupings: Blacks, Native Americans, Hispanics, families with children, unmarried, and younger respondents reported higher SBQ\u2010R scores than their counterparts (p < .000). Regression results confirm these bivariate differences and also reveal that risk factors (food insecurity, physical symptoms, and CES\u2010D symptomatology) are positive and significantly related to suicidality (p < .000). Additionally, resource measures are significant and negatively related to suicidality (p < .000). CONCLUSIONS: These results provide some insight on the impact COVID\u201019 is having on the general U.S. population. Practitioners should be prepared for what will likely be a significant mental health fall\u2010out in the months and years ahead.", "qid": 41, "docid": "jx8eb28j", "rank": 5, "score": 13.599900245666504}, {"content": "Title: How Bad Is It? Suicidality in the Middle of the COVID-19 Pandemic Content: OBJECTIVE: The current paper examines the intersection between social vulnerability, individual risk, and social/psychological resources with adult suicidality during the COVID-19 pandemic. METHOD: Data come from a national sample (n =10, 368) of U.S. adults. Using an online platform, information was gathered the third week of March 2020, and post-stratification weighted to proportionally represent the U.S. population in terms of age, gender, race/ethnicity, income, and geography. RESULTS: Nearly 15 percent of sampled respondents were categorized as high risk, scoring 7+ on the Suicide Behaviors Questionnaire-Revised (SBQ-R). This level of risk varied across social vulnerability groupings: Blacks, Native Americans, Hispanics, families with children, unmarried, and younger respondents reported higher SBQ-R scores than their counterparts (p < 0.000). Regression results confirm these bivariate differences, and also reveal that risk factors (food insecurity, physical symptoms, and CES-D symptomatology) are positive and significantly related to suicidality (p < 0.000). Additionally, resource measures are significant and negatively related to suicidality (p < 0.000). CONCLUSIONS: These results provide some insight on the impact COVID-19 is having on the general U.S. POPULATION: Practitioners should be prepared for what will likely be a significant mental health fall-out in the months and years ahead.", "qid": 41, "docid": "m00xtpmx", "rank": 6, "score": 13.599899291992188}, {"content": "Title: This Time Must Be Different: Disparities During the COVID-19 Pandemic Content: African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.", "qid": 41, "docid": "fsid4a39", "rank": 7, "score": 13.40149974822998}, {"content": "Title: Stay-at-Home Orders, African American Population, Poverty and State-level Covid-19 Infections: Are there associations? Content: Importance: To cope with the continuing COVID-19 pandemic, state and local health officials need information on the effectiveness of policies aimed at curbing contagion, as well as area-specific socio-demographic characteristics that can portend vulnerability to the disease. Objective: To investigate whether state-imposed stay-at-home orders, African American population in the state, state poverty and other state socio-demographic characteristics, were associated with the state-level incidence of COVID-19 infection. Design, Setting, Participants: State-level, aggregated, publicly available data on positive COVID-19 cases and tests were used. The period considered was March 1st -May 4th. All U.S. states except Washington were included. Outcomes of interest were daily cumulative and daily incremental COVID-19 infection rates. Outcomes were log-transformed. Log-linear regression models with a quadratic time-trend and random intercepts for states were estimated. Covariates included log-transformed test-rates, a binary indicator for stay-at-home, percentage of African American, poverty, percentage elderly, state population and prevalence of selected comorbidities. Binary fixed effects for date each state first started reporting test data were included. Results: Stay-at-home orders were associated with decreases in cumulative ({beta}:-1.23; T-stat: -6.84) and daily ({beta}:-0.46; T-stat: -2.56) infection-rates. Predictive analyses indicated that expected cumulative infection rates would be 3 times higher and expected daily incremental rates about 60% higher in absence of stay-at-home orders. Higher African American population was associated with higher cumulative ({beta}: 0.08; T-stat: 4.01) and daily ({beta}: 0.06; T-stat: 3.50) rates. State poverty rates had mixed results and were not robust to model specifications. There was strong evidence of a quadratic daily trend for cumulative and daily rates. Results were largely robust to alternate specifications. Conclusions: We find evidence that stay-at-home orders, which were widely supported by public-health experts, helped to substantially curb COVID-19 infection-rates. As we move to a phased re-opening, continued precautions advised by public-health experts should be adhered to. Also, a larger African American population is strongly associated with incidence of COVID-19 infection. Policies and resources to help mitigate African American vulnerability to COVID-19 is an urgent public health and social justice issue, especially since the ongoing mass protests against police brutality may further exacerbate COVID-19 contagion in this community.", "qid": 41, "docid": "csujgaae", "rank": 8, "score": 13.258299827575684}, {"content": "Title: Racial Disparity of Coronavirus Disease 2019 (COVID-19) in African American Communities Content: The COVID-19 pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new, but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (Black) community, and suggest a multifaceted approach to addressing these healthcare disparities. Of note, terminology from survey data cited for this article varied from Blacks, African Americans or both; for consistency, we use African Americans throughout.", "qid": 41, "docid": "bgpep5lc", "rank": 9, "score": 13.189800262451172}, {"content": "Title: Differential expression of COVID-19-related genes in European Americans and African Americans Content: The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington\u2019s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.", "qid": 41, "docid": "miayce9l", "rank": 10, "score": 13.096699714660645}, {"content": "Title: Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study Content: Background The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. Methods We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. Results We predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R 0 . The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. Discussion In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.", "qid": 41, "docid": "xtpa84h2", "rank": 11, "score": 13.066100120544434}, {"content": "Title: Socioeconomic Correlates of Obesity in African-American and Caribbean-Black Men and Women Content: The high prevalence of obesity among Black Americans warrants additional investigation into its relationship with socioeconomic position (SEP), sex, and ethnicity. This cross-sectional study utilizes 2001\u20132003 data from the National Survey of American Life, a nationally representative sample of 3570 African-Americans and 1621 Caribbean-Blacks aged 18 years and older. Multivariate logistic regression models stratified by ethnicity and sex describe the independent associations between obesity and multilevel socioeconomic factors after adjustment for age, other SEP measures at the individual, family and neighborhood levels, and health behaviors such as physical activity, alcohol intake, and smoking. A positive relationship was observed between obesity and family income among African-American and Caribbean-Black men. Receipt of public assistance was a strongly associated factor for obesity in Caribbean-Black men and women. Among African-American women, inverse relationships were observed between obesity and education, occupation, and family income; residence within a neighborhood with a supermarket also decreased their odds of obesity. Residence in a neighborhood with a park decreased the odds of obesity only among African-American men, whereas residence in a neighborhood with a supermarket decreased the odds of obesity among Caribbean-Black men. The social patterning of obesity by individual, household, and neighborhood socioeconomic resources differs for African-American and Caribbean-Black men and women within these cross-sectional analyses; an appreciation of these differences may be a prerequisite for developing effective weight control interventions and policies for these two populations.", "qid": 41, "docid": "1xrq8cg9", "rank": 12, "score": 12.791600227355957}, {"content": "Title: Differences in race and other state\u2010level characteristics and associations with mortality from COVID\u201019 infection Content: As reporting of COVID\u201019 at the US state level has become more granular, many states have reported a higher proportion of deaths among African\u2010Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital\u2010beds/ventilators per\u2010capita), median household income and high\u2010school graduation rates. We report a higher death rate among states with a greater proportion of African\u2010American residents despite adjusting for case rates and state\u2010level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "rxgnrrx8", "rank": 13, "score": 12.726099967956543}, {"content": "Title: Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults Content: Importance: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Objective: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. Design, Setting, and Participants: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. Main Outcomes and Measures: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. Results: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19-related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning &#8805;$100\u00e2\u0080\u00af000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (-9.4 percentage points; 95% CI, -13.1 to -5.7 percentage points; P < .001), Hispanic respondents (-4.8 percentage points; 95% CI, -8.9 to -0.77 percentage points; P = .02), and people younger than 30 years (-10.3 percentage points; 95% CI, -14.1 to -6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. Conclusions and Relevance: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "0iy8stse", "rank": 14, "score": 12.471699714660645}, {"content": "Title: Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults Content: IMPORTANCE: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. OBJECTIVE: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. DESIGN, SETTING, AND PARTICIPANTS: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. MAIN OUTCOMES AND MEASURES: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. RESULTS: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19\u2013related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning \u2265$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (\u22129.4 percentage points; 95% CI, \u221213.1 to \u22125.7 percentage points; P < .001), Hispanic respondents (\u22124.8 percentage points; 95% CI, \u22128.9 to \u22120.77 percentage points; P = .02), and people younger than 30 years (\u221210.3 percentage points; 95% CI, \u221214.1 to \u22126.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. CONCLUSIONS AND RELEVANCE: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "zz299uk5", "rank": 15, "score": 12.471698760986328}, {"content": "Title: Are African American and Hispanics Disproportionately Affected by COVID-19 Because of Higher Obesity Rates? Content: INTRODUCTION: On March 13, 2020 the WHO declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in African American and Hispanics. The aim of this manuscript is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as it relates to the obesity rates to see whether this issue merits further evaluation. METHODS: COVID-19 data was obtained from the official New York (NY) authorities in relation to total number of cases in the different boroughs of NYC. Age adjusted COVID-19 related mortality rates of the different ethnic groups were also obtained. This data was cross compared to historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The two NYC boroughs that have the highest mortality rates are The Bronx (6%) and Brooklyn (5.4%). Both The Bronx and Brooklyn were also found to have the highest obesity rates 32% and 27% respectively. The two ethnic groups with the highest obesity rates (Hispanics and African Americans) were also found to have the highest age adjusted mortality rates per 100,000 compared to the other ethnic groups (22.8% and 19.8% respectively). CONCLUSION: Hispanics and African Americans in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.", "qid": 41, "docid": "fvkr77sf", "rank": 16, "score": 12.447999954223633}, {"content": "Title: The Influence of Contextual Factors on the Initial Phases of the COVID-19 Outbreak across U.S. Counties Content: Objectives: The COVID-19 pandemic in early 2020 poses an unprecedented threat to the health and economic prosperity of the world's population. Given incomplete reporting of contextual disaggregation in cumulative case data reported by health departments in the U.S., this research links county- and state-level characteristics to the COVID-19 outbreak. Methods: A statistical exponential growth model is estimated to describe the outbreak rate using publicly available county-level outbreak data. County- and state-level effects are simultaneously tested with a multilevel linear model using full maximum likelihood. Results: Mirroring findings from international cultural research, collectivism as a value is positively associated with the outbreak rate. The racial and ethnic composition of counties contributes to differences in the outbreak, with Black/African and Asian Americans being more affected. As expected, counties with a higher median age have a stronger outbreak, and so do counties with more people below the age of 18. Higher income, education, and personal health are generally associated with a lower outbreak. Contrariwise, obesity is negatively and significantly related to the outbreak, in agreement with the value expectancy concepts of the health belief model. Smoking is negatively related, but only directionally informative. Air pollution is another significant contributor to the outbreak, but population density does not give statistical significance. Conclusions: The results show that contextual factors influence the initial outbreak of COVID-19. Because of a high intrastate and intercounty variation in these factors, policy makers need to look at pandemics from the smallest subdivision possible, so that countermeasures can be implemented effectively.", "qid": 41, "docid": "ctg6waey", "rank": 17, "score": 12.415900230407715}, {"content": "Title: A DISSYMMETRY IN THE FIGURES RELATED TO THE COVID-19 PANDEMIC IN THE WORLD: WHAT FACTORS EXPLAIN THE DIFFERENCE BETWEEN AFRICA AND THE REST OF THE WORLD? Content: Humanity has experienced outbreaks for millennia, from epidemics limited to pandemics that have claimed many victims and changed the course of civilizations. The advent of vaccines has eradicated some of the serious pathogens and reduced many others. However, pandemics are still part of our modern world, as we continue to have pandemics as devastating as HIV and as alarming as severe acute respiratory syndrome, Ebola and the Middle East respiratory syndrome. The Covid-19 epidemic with 0-exponential contamination curves reaching 3 million confirmed cases should not have come as a surprise, nor should it have been the last pandemic in the world. In this article, we try to summarize the lost opportunities as well as the lessons learned, hoping that we can do better in the future. The objective of this study is to relate the situation of Covid-19 in African countries with those of the countries most affected by the pandemic. It also allows us to verify how, according to the observed situation, the African ecosystem seems to be much more resilient compared to that of other continents where the number of deaths is in the thousands. To verify this, the diagnosed morbidity and mortality reported for different states of the world are compared to the ages of life and the average annual temperature of these states. The results show that the less dramatic balance of the African continent compared to other continents is partly linked to the relatively high temperatures on the continent but also to the relatively young character of its population.", "qid": 41, "docid": "rozpps6v", "rank": 18, "score": 12.34529972076416}, {"content": "Title: Sickle cell trait and the potential risk of severe coronavirus disease 2019\u2014A mini\u2010review Content: Coronavirus Disease 2019 (COVID\u201019) pandemic is a rapidly evolving public health problem. The severity of COVID\u201019 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID\u201019 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub\u2010Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID\u201019 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.", "qid": 41, "docid": "ubkl52d0", "rank": 19, "score": 12.338500022888184}, {"content": "Title: Racial, Economic and Health Inequality and COVID-19 Infection in the United States Content: Abstract Background: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. Methods: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). Findings: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Interpretation: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access. Keywords: Healthcare Disparities, Health Status Disparities, Socioeconomic Factors, COVID-19, Economic Inequality, Racial Disparity, United States, Population-Based Analysis.", "qid": 41, "docid": "alrf67ep", "rank": 20, "score": 12.328100204467773}, {"content": "Title: Higher Obesity Trends Among African Americans Are Associated with Increased Mortality in Infected COVID-19 Patients Within the City of Detroit Content: As the city of Detroit raids itself of deaths by shifting from homicides, COVID-19 infection continues to harrow the city with more deaths. From March 19 to May 15, more Detroiters died in 2 months than were killed in 2 years of city homicides. African Americans or Blacks (highest-risk phenotypes) developing COVID-19 infection are more likely to die disproportionately. The confluence of diabetes, hypertension, cardiovascular disease, and the higher prevalence of obesity among Blacks have provided the needed environment for viruses like COVID-19 to thrive and cause serious infections. The purpose of this study is to connect mortality rates from COVID-19 infection to increasing obesity trends among African Americans within the city of Detroit. Statistical analyses were conducted using SPSS ver. 23. Results showed that the highest mortality rates among African Americans occurred more in the obese individuals infected with COVID-19 in the city of Detroit. Out of 1930 deaths from COVID-19 infections, 733 deaths were due to obesity alone in patients without reported comorbid conditions like diabetes, hypertension, and cardiovascular disease. Mortality rate for both male and female African Americans amounted to a total of 11.9%. Thirty-eight percent of reported COVID-19-infected African Americans were obese. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00385-y) contains supplementary material, which is available to authorized users.", "qid": 41, "docid": "753klfdp", "rank": 21, "score": 12.307999610900879}, {"content": "Title: Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States Content: Coronavirus disease 2019 (Covid-19) has devastated global populations and has had a large impact in the United States with the number of infections and deaths growing exponentially. Using a smooth generalized additive model with quasipoisson counts for total infections and deaths, we developed a county-level predictive model that included population demographics, social characteristics, social distancing, and testing data. This model strongly predicted the actual US distribution of Covid-19, accounting for 94.8% of spatial-temporal variation in total infections and 99.3% in Covid-19 related fatalities from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans had a higher number of confirmed infections adjusted for county population. Social distancing measured by the change in the rate of human encounter per km2 relative to pre-covid-19 national average was associated with slower rate of Covid-19 infections, whereas higher testing was associated with higher number of infections. The number of people infected was increasing, however, the rate of increase in new infections was starting to show signs of plateauing starting from the second week of April. Our model projects 2.11 million people to test positive for Covid-19 and 122,951 fatalities by June 1, 2020. Importantly, our model suggests strong social differences in the infections and deaths across US communities, and inequities in areas with larger African American minorities and higher poverty index expected to show higher rates of Covid-19 infections and deaths. Preventive steps including social distancing and community closures have been a cornerstone in stopping the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in the disease transmission is essential to understand current disease distribution, predict future distribution, and plan additional preventive steps.", "qid": 41, "docid": "6wqxcshu", "rank": 22, "score": 12.268500328063965}, {"content": "Title: Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be Content: African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system.", "qid": 41, "docid": "1lw5vbu9", "rank": 23, "score": 12.239299774169922}, {"content": "Title: African American children are at higher risk for COVID\u201019 infection Content: Infection by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), the viral etiology of the novel coronavirus disease 2019 (COVID\u201019), was first reported in Wuhan, China in late 2019. Peculiarly, the virus has not caused significant impact on pediatric populations, unlike other coronaviruses (1). Children comprise only 1.7% of COVID\u201019 positive cases in the United States (2). Furthermore, children are noted to have a milder disease course (3, 4). However, much is unknown about the age, gender and race risk factors of COVID\u201019 among children. There has been recent evidence suggestive of higher rates of COVID\u201019 and related fatality rates in African American adult communities around the United States(5). However, there is limited data, to our knowledge, whether any race or ethnicity group is at higher risk for COVID\u201019 infection in children.", "qid": 41, "docid": "b5lrwe3i", "rank": 24, "score": 12.208700180053711}, {"content": "Title: Disproportionate COVID-19 Related Mortality Amongst African Americans in Four Southern States in the United States Content: Background African American have been severely affected by COVID-19 noted with the rising mortality rates within the African American community. Health disparities, health inequities and issues with systemic health access are some of the pre-existing issues African American were subjected to within the southern states in the United States. Second, social distancing is a critical non-pharmacological intervention to reduce the spread of COVID-19. However, social distancing was not practical and presented a challenge within the African American community, specifically, in the southern states. Objective This article assesses the effect of COVID-19 on African American in the southern states. Methodology This short communication queried the publicly available Department of Health statistics on COVID-19 related mortality and underlying health conditions in four southern states (Alabama [AL], Georgia [GA], Louisiana [LA] and Mississippi [MS]) with a high proportion of African American residents. Second, unacast COVID-19 toolkit was used to derive a social distancing (SD) grade for any given state, based on three different metrics: (i) percent change in average distance travelled (ii) percent change in non-essential visits and (iii) decrease in human encounters (compared to national baseline). Results Across the four states, on average, as many as 54% of COVID-19 related deaths are in the African American community, although this minority group comprises only 32% of the population cumulatively. This article finds that all four southern states received a social distancing grade of F. COVID-19 have demonstrated that adverse outcomes are higher in individuals with underlying health conditions such as diabetes, cardiovascular diseases, or pre-existing pulmonary compromise. Conclusion Recognizing that there is a great need for African American representation or diversity in the health workforce would be able to better address the health disparities. In addition, the lack of diversity in the healthcare system causes the morbidity and mortality rates to increase in the African American communities because it is not able to address its primary obligations within the African American communities in the southern states during COVID-19 pandemic. These primary obligations are to restore, protect, improve health and to suppress health disparities and inequalities of COVID-19 within in the African American communities. Keywords: COVID-19; African American; Mortality", "qid": 41, "docid": "8yvu9xhw", "rank": 25, "score": 12.172699928283691}, {"content": "Title: Blacks/African Americans are 5 Times More Likely to Develop COVID-19: Spatial Modeling of New York City ZIP Code-level Testing Results Content: Introduction. The population and spatial characteristics of COVID-19 infections are poorly understood, but there is increasing evidence that in addition to individual clinical factors, demographic, socioeconomic and racial characteristics play an important role. Methods. We analyzed positive COVID-19 testing results counts within New York City ZIP Code Tabulation Areas (ZCTA) with Bayesian hierarchical Poisson spatial models using integrated nested Laplace approximations. Results. Spatial clustering accounted for approximately 32% of the variation in the data, with hot spots in all five boroughs. Spatial risk did not correspond precisely to population-based rates of positive tests. The strongest univariate association with positive testing rates was the proportion of residents in a ZIP Code Tabulation Area with Chronic Obstructive Pulmonary Disease (COPD). For every one unit increase in a scaled standardized measure of COPD in a community, there was an approximate 8-fold increase in the risk of a positive COVID-19 test in a ZCTA (Incidence Density Ratio = 8.2, 95% Credible Interval 3.7, 18.3). The next strongest association was with the proportion of Black and African American residents, for which there was a nearly five-fold increase in the risk of a positive COVID-19 test. (IDR = 4.8, 95% Cr I 2.4, 9.7). Increases in the proportion of residents older than 65, housing density and the proportion of residents with heart disease were each associated with an approximate doubling of risk. In a multivariable model including estimates for age, COPD, heart disease, housing density and Black/African American race, the only variables that remained associated with positive COVID-19 testing with a probability greater than chance were the proportion of Black/African American residents and proportion of older persons. Conclusions. The population and spatial patterns of COVID-19 infections differ by race, age, physical environment and health status. Areas with large proportions of Black/African American residents are at markedly higher risk that is not fully explained by characteristics of the environment and pre-existing conditions in the population.", "qid": 41, "docid": "crqvdk4k", "rank": 26, "score": 11.853899955749512}, {"content": "Title: Molecular mechanisms for thrombosis risk in Black people: a role in excess mortality from COVID\u201019 Content: We read with interest your recent article by Fogarty et al, in particular their conclusion that differences in thrombotic risk may contribute to ethnic disparities in mortality from Covid-19.(1) This is especially important in the UK, where age-sex adjusted hospital death rates for Covid-19 are 2.17 times higher for people with ethnicity recorded as black compared to those recorded as white, and 1.95 higher for those recorded as Asian.(2) This excess mortality persists after adjustment for deprivation, body mass index (BMI), smoking and comorbidities,(2) and despite correction for region, rural or urban living, deprivation, household composition, socioeconomic status, and health.(3) Similar data from the USA shows that in 14 states, African-Americans represent 33% of hospitalisations for Covid-19, despite only making up 14% of the catchment population.(4) Black ethnicity is a construct incorporating diverse populations of African descent. Studies from several communities labelled as black, in particular African-Americans, imply a common increase in thrombotic risk, which may contribute to unexplained ethnic disparities in the UK and USA in Covid-19.", "qid": 41, "docid": "ol2c7f3x", "rank": 27, "score": 11.744600296020508}, {"content": "Title: Impact of essential workers in the context of social distancing for epidemic control Content: Many governments have responded to the ongoing COVID-19 pandemic by imposing social policies that restrict interactions outside of the home, resulting in a large fraction of the workforce either working from home or not working. However, to maintain essential services, a substantial number of workers are not subject to these limitations, and maintain many of their pre-intervention interactions. To explore how interactions among such \"essential\" workers, and between essential workers and the rest of the population, impact disease risk and the effectiveness of pandemic control, we evaluated several models of essential worker interactions within a standard epidemiology framework. The models were designed to correspond to key characteristics of, respectively, cashiers, factory employees, and healthcare workers. We find in all three models that essential workers are at substantially elevated risk of infection compared to the rest of the population, and that increasing the numbers of essential workers necessitates the imposition of more stringent interaction controls on the rest of the population in order to manage the pandemic. However, different archetypes of essential workers differ in both their individual probability of infection and impact on the broader pandemic, highlighting the need to understand and target for intervention the specific risks faced by different groups of essential workers.", "qid": 41, "docid": "9q0b0nio", "rank": 28, "score": 11.706100463867188}, {"content": "Title: Reparations for Black American Descendants of Persons Enslaved in the U.S. and Their Estimated Impact on SARS-CoV-2 Transmission Content: Background In the United States, Black Americans are suffering from significantly disproportionate incidence and mortality rates of COVID-19. The potential for racial-justice interventions, including reparations payments, to ameliorate these disparities has not been adequately explored. Methods We compared the COVID-19 time-varying Rt curves of relatively disparate polities in terms of social equity (South Korea vs. Louisiana). Next, we considered a range of reproductive ratios to back-calculate the transmission rates {beta}i[->]j for 4 cells of the simplified next-generation matrix (from which R0 is calculated for structured models) for the outbreak in Louisiana. Lastly, we modeled the effect that monetary payments as reparations for Black American descendants of persons enslaved in the U.S. would have had on pre-intervention {beta}i[->]j. Results Once their respective epidemics begin to propagate, Louisiana displays Rt values with an absolute difference of 1.3 to 2.5 compared to South Korea. It also takes Louisiana more than twice as long to bring Rt below 1. We estimate that increased equity in transmission consistent with the benefits of a successful reparations program (reflected in the ratio {beta}b[->]b / {beta}w[->]w) could reduce R0 by 31 to 68%. Discussion While there are compelling moral and historical arguments for racial injustice interventions such as reparations, our study describes potential health benefits in the form of reduced SARS-CoV-2 transmission risk. As we demonstrate, a restitutive program targeted towards Black individuals would not only decrease COVID-19 risk for recipients of the wealth redistribution; the mitigating effects would be distributed across racial groups, benefitting the population at large.", "qid": 41, "docid": "y60yra4r", "rank": 29, "score": 11.630000114440918}, {"content": "Title: Genetic Ancestry for Sleep Research: Leveraging Health Inequalities to Identify Causal Genetic Variants. Content: Recent evidence has highlighted the health inequalities in sleep behaviors and sleep disorders that adversely affect outcomes in select populations, including African-American and Hispanic-American subjects. Race-related sleep health inequalities are ascribed to differences in multilevel and interlinked health determinants, such as sociodemographic factors, health behaviors, and biology. African-American and Hispanic-American subjects are admixed populations whose genetic inheritance combines two or more ancestral populations originating from different continents. Racial inequalities in admixed populations can be parsed into relevant groups of mediating factors (environmental vs genetic) with the use of measures of genetic ancestry, including the proportion of an individual's genetic makeup that comes from each of the major ancestral continental populations. This review describes sleep health inequalities in African-American and Hispanic-American subjects and considers the potential utility of ancestry studies to exploit these differences to gain insight into the genetic underpinnings of these phenotypes. The inclusion of genetic approaches in future studies of admixed populations will allow greater understanding of the potential biological basis of race-related sleep health inequalities.", "qid": 41, "docid": "7rc6d2gf", "rank": 30, "score": 11.604100227355957}, {"content": "Title: The potential effect of the African population age structure on COVID-19 mortality Content: Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.", "qid": 41, "docid": "vzmn6zep", "rank": 31, "score": 11.542499542236328}, {"content": "Title: Coronavirus Disease Health Care Delivery Impact on African Americans Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 1.5 million individuals and led to over 91, 000 deaths in the United States (US) alone as of May 20th, 2020. Minority populations, however, continue to be a high-risk population to contract the SARS-CoV-2 infection. While socioeconomic inequality may help to explain why minority ethnic populations are contracting the SARS-CoV-2 in larger proportions, the reason for elevated mortality rates in African Americans is still unknown. African Americans are less likely than whites to utilize high-quality hospitals, ambulatory care services, and regular primary care providers; this is most likely a result of barriers to accessing high quality treatment, as African Americans have substantially higher uninsured rates. However, previous reports have shown that regardless of insurance status, African Americans are more likely to be directed toward lower quality treatment plans compared to their white counterparts, and that physicians carry implicit biases that negatively impact treatment regimens for these minority populations. While income, education, and access to healthcare should be revised in due time, in the short term physicians should do everything possible to learn about implicit biases that may exist in healthcare, as the first step to minimize implicit biases is to recognize that they exist.", "qid": 41, "docid": "7k4reog4", "rank": 32, "score": 11.398200035095215}, {"content": "Title: COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection Content: Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy. Main Outcomes and Measure: Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death. Results: For the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123). Conclusions and Relevance: Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.", "qid": 41, "docid": "y69w57wq", "rank": 33, "score": 11.353899955749512}, {"content": "Title: Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan Content: The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "423uero3", "rank": 34, "score": 11.301600456237793}, {"content": "Title: Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan. Content: The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "zdmoifko", "rank": 35, "score": 11.301599502563477}, {"content": "Title: Optimized lockdown strategies for curbing the spread of COVID-19: A South African case study Content: To curb the spread of COVID-19, many governments around the world have implemented tiered lockdowns with varying degrees of stringency. Lockdown levels are typically increased when the disease spreads and reduced when the disease abates. A predictive control approach is used to develop optimized lockdown strategies for curbing the spread of COVID-19. These strategies are then applied to South African data. The South African case is of immediate interest as the number of confirmed infectious cases does not appear to have peaked yet (at the time of writing), while at the same time the South African government is busy reducing the degree of lockdown. An epidemiological model for the spread of COVID-19 in South Africa was previously developed, and is used in conjunction with a hybrid model predictive controller to optimize lockdown management under different policy scenarios. Scenarios considered include how flatten the curve to a level that the healthcare system can cope with, how to balance lives and livelihoods, and what impact the compliance of the population to the lockdown measures has on the spread of COVID-19.", "qid": 41, "docid": "8wpccy2y", "rank": 36, "score": 11.27929973602295}, {"content": "Title: Why African Americans Are a Potential Target for COVID-19 Infection in the United States Content: Since the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic, significant changes have occurred in the United States as the infection spread reached and passed its exponential phase. A stringent analysis of COVID-19 epidemiologic data requires time and would generally be expected to happen with significant delay after the exponential phase of the disease is over and when the focus of the health care system is diverted away from crisis management. Although much has been said about high-risk groups and the vulnerability of the elderly and patients with underlying comorbidities, the impact of race on the susceptibility of ethnic minorities living in indigent communities has not been discussed in detail worldwide and specifically in the United States. There are currently some data on disparities between African American and Caucasian populations for COVID-19 infection and mortality. While health care authorities are reorganizing resources and infrastructure to provide care for symptomatic COVID-19 patients, they should not shy away from protecting the general public as a whole and specifically the most vulnerable members of society, such as the elderly, ethnic minorities, and people with underlying comorbidities.", "qid": 41, "docid": "wwucpqin", "rank": 37, "score": 11.276900291442871}, {"content": "Title: Making sense of the U.S. COVID-19 pandemic response: A policy regime perspective Content: On March 26, 2020, 3 months after Chinese authorities admitted to a novel coronavirus outbreak and 10 weeks after the first infection was documented on American soil, the U.S. led the world in COVID-19 cases. While the State Department touted the U.S. as \u201cleading the world\u2019s humanitarian and health assistance response to the COVID-19 pandemic,\u201d media accounts more often applied terms like \u201cmuddled\u201d and \u201cconfused.\u201d In this essay, we step back to consider what it takes to bring about swift and coordinated action in pandemic response, and what has impeded such a response thus far in U.S. efforts to address COVID-19. Informed by a policy regime perspective, we argue that the response has been handicapped by deficient political commitment and unclear goals, dysfunctional institutional dynamics\u2014from bureaucratic silos to mismatched institutions, and inertia from partisan and economic interests. We conclude that the incoherence of the U.S. response to date has further eroded its already undermined legitimacy, and more importantly, has helped engender negative feedback that threatens the near-term durability of response measures, with grave consequences.", "qid": 41, "docid": "50njcfe6", "rank": 38, "score": 11.274299621582031}, {"content": "Title: E-SHOPPING changes and the state of E-grocery shopping in the U.S. evidence from national travel and time use surveys Content: Abstract In spite of the popularity of e-shopping, only 16% of US adults have ordered groceries online, and 7 out of 10 of those who currently buy groceries online do so at most twice a month. Understanding the determinants of e-grocery shopping is important for grocers, supply chain managers, and urban planners. In this context, we first explore how deliveries from online shopping have been changing over time. From our analysis of the 2009 and 2017 National Household Travel Surveys, we found that online shopping has been embraced by increasingly diverse households, although income, education, and some racial/ethnic differences persist. Our analysis of the 2017 American Time Use Survey shows that Americans are 24 times more likely to shop for groceries in stores than online. Moreover, in-store grocery shoppers are more likely to be female and unemployed, but less likely to belong to younger generations, to have less than a college degree, or to be African American. The gender imbalance in grocery shopping is larger online than in stores, but e-grocery shoppers do not otherwise differ from the general population. Future travel and e-shopping surveys (especially for e-grocery) should combine time use and travel questions with retrospective questions about online purchases.", "qid": 41, "docid": "mrace6ux", "rank": 39, "score": 11.215999603271484}, {"content": "Title: Pseudo-Likelihood Based Logistic Regression for Estimating COVID-19 Infection and Case Fatality Rates by Gender, Race, and Age in California Content: In emerging epidemics, early estimates of key epidemiological characteristics of the disease are critical for guiding public policy. In particular, identifying high risk population subgroups aids policymakers and health officials in combatting the epidemic. This has been challenging during the coronavirus disease 2019 (COVID-19) pandemic, because governmental agencies typically release aggregate COVID-19 data as marginal summary statistics of patient demographics. These data may identify disparities in COVID-19 outcomes between broad population subgroups, but do not provide comparisons between more granular population subgroups defined by combinations of multiple demographics. We introduce a method that overcomes the limitations of aggregated summary statistics and yields estimates of COVID-19 infection and case fatality rates --- key quantities for guiding public policy related to the control and prevention of COVID-19 --- for population subgroups across combinations of demographic characteristics. Our approach uses pseudo-likelihood based logistic regression to combine aggregate COVID-19 case and fatality data with population-level demographic survey data to estimate infection and case fatality rates for population subgroups across combinations of demographic characteristics. We illustrate our method on California COVID-19 data to estimate test-based infection and case fatality rates for population subgroups defined by gender, age, and race and ethnicity. Our analysis indicates that in California, males have higher test-based infection rates and test-based case fatality rates across age and race/ethnicity groups, with the gender gap widening with increasing age. Although elderly infected with COVID-19 are at an elevated risk of mortality, the test-based infection rates do not increase monotonically with age. LatinX and African Americans have higher test-based infection rates than other race/ethnicity groups. The subgroups with the highest 5 test-based case fatality rates are African American male, Multi-race male, Asian male, African American female, and American Indian or Alaska Native male, indicating that African Americans are an especially vulnerable California subpopulation.", "qid": 41, "docid": "4cz3nc4b", "rank": 40, "score": 11.172300338745117}, {"content": "Title: Clinical Characteristics and Outcomes of Community- and Hospital-Acquired Acute Kidney Injury with COVID-19 in a US Inner City Hospital System Content: INTRODUCTION: Emerging data have described poor clinical outcomes from infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) among African American patients and those from underserved socioeconomic groups. We sought to describe the clinical characteristics and outcomes of acute kidney injury (AKI) in this special population. METHODS: This is a retrospective study conducted in an underserved area with a predominance of African American patients with coronavirus disease 2019 (COVID-19). Descriptive statistics were used to characterize the sample population. The onset of AKI and relation to clinical outcomes were determined. Multivariate logistic regression was used to determine factors associated with AKI. RESULTS: Nearly half (49.3%) of the patients with COVID-19 had AKI. Patients with AKI had a significantly lower baseline estimated glomerular filtration rate (eGFR) and higher FiO2 requirement and D-dimer levels on admission. More subnephrotic proteinuria and microhematuria was seen in these patients, and the majority had a pre-renal urine electrolyte profile. Patients with hospital-acquired AKI (HA-AKI) as opposed to those with community-acquired AKI (CA-AKI) had higher rates of in-hospital death (52 vs. 23%, p = 0.005), need for vasopressors (42 vs. 25%, p = 0.024), and need for intubation (55 vs. 25%, p = 0.006). A history of heart failure was significantly associated with AKI after adjusting for baseline eGFR (OR 3.382, 95% CI 1.121-13.231, p = 0.032). CONCLUSION: We report a high burden of AKI among underserved COVID-19 patients with multiple comorbidities. Those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKI. A history of heart failure is an independent predictor of AKI in patients with COVID-19.", "qid": 41, "docid": "17kk4w0m", "rank": 41, "score": 11.13949966430664}, {"content": "Title: Clinical Characteristics and Outcomes of Community- and Hospital-Acquired Acute Kidney Injury with COVID-19 in a US Inner City Hospital System Content: INTRODUCTION: Emerging data have described poor clinical outcomes from infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) among African American patients and those from underserved socioeconomic groups. We sought to describe the clinical characteristics and outcomes of acute kidney injury (AKI) in this special population. METHODS: This is a retrospective study conducted in an underserved area with a predominance of African American patients with coronavirus disease 2019 (COVID-19). Descriptive statistics were used to characterize the sample population. The onset of AKI and relation to clinical outcomes were determined. Multivariate logistic regression was used to determine factors associated with AKI. RESULTS: Nearly half (49.3%) of the patients with COVID-19 had AKI. Patients with AKI had a significantly lower baseline estimated glomerular filtration rate (eGFR) and higher FiO2 requirement and D-dimer levels on admission. More subnephrotic proteinuria and microhematuria was seen in these patients, and the majority had a pre-renal urine electrolyte profile. Patients with hospital-acquired AKI (HA-AKI) as opposed to those with community-acquired AKI (CA-AKI) had higher rates of in-hospital death (52 vs. 23%, p = 0.005), need for vasopressors (42 vs. 25%, p = 0.024), and need for intubation (55 vs. 25%, p = 0.006). A history of heart failure was significantly associated with AKI after adjusting for baseline eGFR (OR 3.382, 95% CI 1.121\u201313.231, p = 0.032). CONCLUSION: We report a high burden of AKI among underserved COVID-19 patients with multiple comorbidities. Those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKI. A history of heart failure is an independent predictor of AKI in patients with COVID-19.", "qid": 41, "docid": "yb6to2ro", "rank": 42, "score": 11.139498710632324}, {"content": "Title: COVID-19 outcomes, risk factors and associations by race: a comprehensive analysis using electronic health records data in Michigan Medicine Content: Importance: Blacks/African-Americans are overrepresented in the number of COVID-19 infections, hospitalizations and deaths. Reasons for this disparity have not been well-characterized but may be due to underlying comorbidities or sociodemographic factors. Objective: To systematically determine patient characteristics associated with racial/ethnic disparities in COVID-19 outcomes. Design: A retrospective cohort study with comparative control groups. Setting: Patients tested for COVID-19 at University of Michigan Medicine from March 10, 2020 to April 22, 2020. Participants: 5,698 tested patients and two sets of comparison groups who were not tested for COVID-19: randomly selected unmatched controls (n = 7,211) and frequency-matched controls by race, age, and sex (n = 13,351). Main Outcomes and Measures: We identified factors associated with testing and testing positive for COVID-19, being hospitalized, requiring intensive care unit (ICU) admission, and mortality (in/out-patient during the time frame). Factors included race/ethnicity, age, smoking, alcohol consumption, healthcare utilization, and residential-level socioeconomic characteristics (SES; i.e., education, unemployment, population density, and poverty rate). Medical comorbidities were defined from the International Classification of Diseases (ICD) codes, and were aggregated into a comorbidity score. Results: Of 5,698 patients, (median age, 47 years; 38% male; mean BMI, 30.1), the majority were non-Hispanic Whites (NHW, 59.2%) and non-Hispanic Black/African-Americans (NHAA, 17.2%). Among 1,119 diagnosed, there were 41.2% NHW and 37.4% NHAA; 44.8% hospitalized, 20.6% admitted to ICU, and 3.8% died. Adjusting for age, sex, and SES, NHAA were 1.66 times more likely to be hospitalized (95% CI, 1.09-2.52; P=.02), 1.52 times more likely to enter ICU (95% CI, 0.92-2.52; P=.10). In addition to older age, male sex and obesity, high population density neighborhood (OR, 1.27 associated with one SD change [95% CI, 1.20-1.76]; P=.02) was associated with hospitalization. Pre-existing kidney disease led to 2.55 times higher risk of hospitalization (95% CI, 1.62-4.02; P<.001) in the overall population and 11.9 times higher mortality risk in NHAA (95% CI, 2.2-64.7, P=.004). Conclusions and Relevance: Pre-existing type II diabetes/kidney diseases and living in high population density areas were associated with high risk for COVID-19 susceptibility and poor prognosis. Association of risk factors with COVID-19 outcomes differed by race. NHAA patients were disproportionately affected by obesity and kidney disease.", "qid": 41, "docid": "zxb8zfep", "rank": 43, "score": 11.13599967956543}, {"content": "Title: Seizing the Moment: Policy Advocacy to End Mass Incarceration in the Time of COVID-19. Content: The mass human and economic casualties wrought by the COVID-19 pandemic laid bare the deep inequities at the base of the disproportionate losses and suffering experienced by diverse U.S. populations. But the urgency and enormity of unmet needs requiring bold policy action also provided a unique opportunity to learn from and partner with community-based organizations that often are at the frontlines of such work. Following a review of Kingdon's model of the policy-making process, we illustrate how a partnership in a large California county navigated the streams in the policy-making process and used the window of opportunity provided by the pandemic to address a major public health problem: the incarceration of over 2 million people, disproportionately African American and Latinx, in overcrowded, unsafe jails, prisons, and detention centers. We highlight tactics and strategies used, challenges faced, and implications for health educators as policy advocates during and beyond the pandemic.", "qid": 41, "docid": "fe1v252b", "rank": 44, "score": 11.074600219726562}, {"content": "Title: Seizing the Moment: Policy Advocacy to End Mass Incarceration in the Time of COVID-19 Content: The mass human and economic casualties wrought by the COVID-19 pandemic laid bare the deep inequities at the base of the disproportionate losses and suffering experienced by diverse U.S. populations. But the urgency and enormity of unmet needs requiring bold policy action also provided a unique opportunity to learn from and partner with community-based organizations that often are at the frontlines of such work. Following a review of Kingdon's model of the policy-making process, we illustrate how a partnership in a large California county navigated the streams in the policy-making process and used the window of opportunity provided by the pandemic to address a major public health problem: the incarceration of over 2 million people, disproportionately African American and Latinx, in overcrowded, unsafe jails, prisons, and detention centers. We highlight tactics and strategies used, challenges faced, and implications for health educators as policy advocates during and beyond the pandemic.", "qid": 41, "docid": "oo3u783z", "rank": 45, "score": 11.074599266052246}, {"content": "Title: COVID-19-related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids Content: Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity.Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma.Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects.Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to sex, race, and use of ICS.Conclusions: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity.", "qid": 41, "docid": "8re6k952", "rank": 46, "score": 11.006400108337402}, {"content": "Title: Disparities in premature deaths from heart disease--50 States and the District of Columbia, 2001. Content: In 2001, heart disease accounted for approximately 29.0% of deaths among U.S. residents; 16.8% of those deaths occurred among persons aged <65 years. Although mortality rates from heart disease have decreased, the decline has not been uniform for all populations. One of the two overall national health objectives for 2010 is to eliminate health disparities among different segments of the U.S. population. To better understand these disparities, CDC analyzed death certificate data for premature deaths from heart disease occurring in 2001. This report summarizes the results of that analysis, which indicated that the proportion of premature heart disease deaths varied by state and was higher among blacks, American Indians/Alaska Natives (AI/ANs), Asians/Pacific Islanders (A/PIs), and Hispanics. Reducing premature death from heart disease and eliminating disparities will require preventing, detecting, treating, and controlling risk factors for heart disease in young and middle-aged adults.", "qid": 41, "docid": "03q86e1d", "rank": 47, "score": 11.001899719238281}, {"content": "Title: Contemporary and Future Concepts on Hypertension in African Americans: COVID-19 and Beyond Content: BACKGROUND: Cardiovascular disease related mortality is the leading cause of death in the United States, with hypertension being the most prevalent and potent risk factor. For decades hypertension has disproportionately affected African Americans, who also have a higher burden of associated comorbidities including diabetes and heart failure. METHODS: Current literature including guideline reports and newer studies on hypertension in African Americans in PubMed were reviewed. We also reviewed newer publications on the relationship between COVID-19 and cardiovascular disease. FINDINGS: While APOL1 has been theorized in the epidemiology of hypertension, the increased prevalence and associated risks are primarily due to environmental and lifestyle factors. These factors include poor diet, adverse lifestyle, and social determinants. Hypertension control can be achieved by lifestyle modifications such as low sodium diet, weight loss, and adequate physical activity. When lifestyle modifications alone do not adequately control hypertension, a common occurrence among African Americans who suffer with greater prevalence of resistant hypertension, pharmacological intervention is indicated. The efficacy of renal denervation, and the use of sodium-glucose cotransporter 2 and aminopeptidase A inhibitors, have been studied for treatment of resistant hypertension. Furthermore, the recent COVID-19 crisis has been particularly devastating among African Americans who demonstrate increased incidence and poorer health outcomes related to the disease. CONCLUSION: The disparities in outcomes, which are largely attributable to a greater prevalence of comorbidities such as hypertension and obesity, in addition to adverse environmental and socioeconomic factors, highlight the necessity of specialized clinical approaches and programs for African Americans to address longstanding barriers to equitable care.", "qid": 41, "docid": "cn2j9ih4", "rank": 48, "score": 10.954000473022461}, {"content": "Title: Singapore COVID-19 Pandemic Response as a Successful Model Framework for Low-Resource Health Care Settings in Africa? Content: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to spread and evolve across the planet. The crosscutting impacts of the virus, individual country responses to the virus, and the state of preparedness of local public health systems greatly vary across the world. The ostensibly late arrival of the virus in Africa has allowed learning, innovation, and adaptation of methods that have been successful in the early-hit countries. This article analyzes how Singapore has responded to the COVID-19 pandemic and proposes that adaptations of the Singapore pandemic response model would bode well for Africa's response to the COVID-19 pandemic in ways that also take into account regional differences in health care infrastructures, socioeconomic resilience, poverty, and the vast population diversity in the African continent. As the pandemic evolves, the lessons learned in Asia, in particular, and the emerging new experiences in African countries should inform, ideally in real time, how best to steer the world populations into safety, including those in low-resource health care settings. Finally, we note that the current COVID-19 pandemic is also a test for our collective ability to scale and surge public health in response to future and likely equally challenging zoonosis infections that jump from animals to humans, not to mention climate change-related planetary health calamities in the 21st century. Hence, what we learn effectively from the current COVID-19 pandemic shall have broad, enduring, and intergenerational relevance for the future of planetary heath and society.", "qid": 41, "docid": "2y4sjdtm", "rank": 49, "score": 10.945300102233887}, {"content": "Title: Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation Content: Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics is that it disproportionately affects people from Black and African American backgrounds creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts, but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.", "qid": 41, "docid": "3lkahro8", "rank": 50, "score": 10.928799629211426}, {"content": "Title: COVID-19\u2013related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids Content: Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity. Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma. Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects. Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to sex, race, and use of ICS. Conclusions: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity.", "qid": 41, "docid": "x7lw525m", "rank": 51, "score": 10.85949993133545}, {"content": "Title: ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity Content: The susceptibility of different populations to the SARS-CoV-2 infection is not yet understood. A deeper analysis of the genomes of individuals from different populations might explain their risk for infection. In this study, a combined analysis of ACE2 coding variants in different populations and computational chemistry calculations are conducted in order to probe the potential effects of ACE2 coding variants on SARS-CoV-2/ACE2 binding affinity. Our study reveals novel interaction data on the variants and SARS-CoV-2. We could show that ACE2-K26R; which is more frequent in the Ashkenazi Jewish population decrease the electrostatic attraction between SARS-CoV-2 and ACE2. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R were found to increase the electrostatic attraction and increase the binding to SARS-CoV-2; ordered by the strength of binding from weakest to strongest. I468V, R219C, K341R, D206G and G211R were more frequent in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. SARS-CoV-2/ACE2 interface in the WT protein and corresponding variants is showed to be a dominated by van der Waals (vdW) interactions. All the mutations except K341R induce an increase in the vdW attractions between the ACE2 and the SARS-CoV-2. The largest increase of is observed for the R219C mutant.", "qid": 41, "docid": "qp3ianzf", "rank": 52, "score": 10.856900215148926}, {"content": "Title: Disparities in COVID-19 Reported Incidence, Knowledge, and Behavior Content: Abstract Background: Data from the COVID-19 pandemic in the United States show large differences in hospitalizations and mortality across race and geography. However, there is limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Methods: A sample of 5,198 respondents in the United States (80% population representative, 20% oversample of hotspot areas in New York City, Seattle, New Orleans, and Detroit) was conducted from March 29th to April 13th to measure differences in knowledge, beliefs and behavior regarding COVID-19. Linear regression was used to understand racial, geographic, political, and socioeconomic differences in COVID-19 reported incidence knowledge, and behaviors after adjusting for state-specific and survey date fixed effects. Results: The largest differences in COVID-19 knowledge and behaviors are associated with race/ethnicity, gender, and age. African-Americans, men, and people <55 years old are less likely to know how the disease is spread, less likely to know symptoms of COVID-19, wash their hands less frequently, and leave the home more often. Differences by income, political orientation, and living in a hotspot area are much smaller. Conclusions: There are wide gaps in COVID-19 reported incidence, knowledge regarding disease spread and symptoms, and in social distancing behavior. The findings suggest more effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "92o3dujh", "rank": 53, "score": 10.843299865722656}, {"content": "Title: Sickle Cell Trait and The Potential Risk of Severe Coronavirus Disease 2019- A Mini-Review Content: Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 amongst African Americans, although detailed epidemiological study data is pending. Sickle Cell Disease (SCD) disproportionately affect Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America) and some Mediterranean countries. The carrier frequency for SCD is high amongst African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.", "qid": 41, "docid": "7z5rkti3", "rank": 54, "score": 10.76509952545166}, {"content": "Title: Racial Variations in COVID\u201019 Deaths May Be Due to Androgen Receptor Genetic Variants Associated with Prostate Cancer and Androgenetic Alopecia. Are Anti\u2010Androgens a Potential Treatment for COVID\u201019? Content: Racial disparities in COVID\u201019 infection rates and disease severity are due to a multifactorial etiology that can include socioeconomic as well as other factors. Nevertheless, genetic factors in different ethnic groups often contribute to disease severity and treatment response. In particular, the frequency of genetic variations in the androgen receptor differs by ethnicity and gender. For example, the increased prevalence of prostate cancer and androgenetic alopecia among African Americans correlates with the frequency of these variants. In this communication, we propose that androgens may be implicated in COVID\u201019 disease severity. As such, special attention may need to be given to African Americans infected by the SARS\u2010CoV\u20102 virus. Finally, if a link to genetic variations in the androgen receptor and COVID\u201019 disease severity can be established, it would suggest new treatment options.", "qid": 41, "docid": "rk6h1vka", "rank": 55, "score": 10.75469970703125}, {"content": "Title: Trading Privacy for the Greater Social Good: How Did America React During COVID-19? Content: Digital contact tracing and analysis of social distancing from smartphone location data are two prime examples of non-therapeutic interventions used in many countries to mitigate the impact of the COVID-19 pandemic. While many understand the importance of trading personal privacy for the public good, others have been alarmed at the potential for surveillance via measures enabled through location tracking on smartphones. In our research, we analyzed massive yet atomic individual-level location data containing over 22 billion records from ten Blue (Democratic) and ten Red (Republican) cities in the U.S., based on which we present, herein, some of the first evidence of how Americans responded to the increasing concerns that government authorities, the private sector, and public health experts might use individual-level location data to track the COVID-19 spread. First, we found a significant decreasing trend of mobile-app location-sharing opt-out. Whereas areas with more Democrats were more privacy-concerned than areas with more Republicans before the advent of the COVID-19 pandemic, there was a significant decrease in the overall opt-out rates after COVID-19, and this effect was more salient among Democratic than Republican cities. Second, people who practiced social distancing (i.e., those who traveled less and interacted with fewer close contacts during the pandemic) were also less likely to opt-out, whereas the converse was true for people who practiced less social-distancing. This relationship also was more salient among Democratic than Republican cities. Third, high-income populations and males, compared with low-income populations and females, were more privacy-conscientious and more likely to opt-out of location tracking.", "qid": 41, "docid": "ihijerw1", "rank": 56, "score": 10.717000007629395}, {"content": "Title: Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans? Content: Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.", "qid": 41, "docid": "q0tu1pja", "rank": 57, "score": 10.691200256347656}, {"content": "Title: Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties Content: BACKGROUND: Recent news reports state that racial minority groups, such as African\u2013Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African\u2013Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian\u2013Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African\u2013Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "qid": 41, "docid": "58ye9c5a", "rank": 58, "score": 10.68179988861084}, {"content": "Title: Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties Content: BACKGROUND: Recent news reports state that racial minority groups, such as African-Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African-Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian-Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African-Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "qid": 41, "docid": "ne552y3i", "rank": 59, "score": 10.681798934936523}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Since the emergence of the COVID-19 pandemic in December 2019 in Wuhan, China, there have been nearly 6,663,304 confirmed cases of COVID-19, including 392,802 deaths, worldwide as of 10:00 CEST 06 June 2020. In Africa, 152,442 COVID-19 cases and 4334 deaths have been reported as of 02 June 2020. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, and the rest of world, has had to swiftly undertake the necessary measures to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting systems, and insufficient numbers of medical staff. The COVID-19 pandemic poses a great threat to most African countries, from cities to rural areas, and has created a strong demand on already scarce resources. Intense mobilization of additional resources is required to implement established emergency contingency measures. Measures to prevent the spread of COVID-19 include closure of borders and restricting movement of people within a country; this has resulted in the tourism sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 41, "docid": "h3czhqtt", "rank": 60, "score": 10.663000106811523}, {"content": "Title: What works and what does not work in response to COVID-19 prevention and control in Africa Content: Abstract Since the emergence of the pandemic in December 2019 in Wuhan, China, as of 10:00 CEST, June 6, 2020, there have been nearly 6,663,304 confirmed cases of COVID-19 including 392,802 deaths worldwide. In Africa, as of June 2, 2020, a total of 152,442 COVID-19 cases and 4334 deaths have been reported. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, together with the rest of world have had to swiftly undertake measures necessary to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting system and insufficient number of medical staff. The COVID-19 pandemic poses a great threat to most African countries from cities to rural areas and has created a strong demand on already scarce resources and requires an intense mobilization of additional resources to implement established emergency contingency measures. Closure of borders and movements of people restrictions within the country as measures to prevent the spread of COVID-19; this has resulted in the sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.", "qid": 41, "docid": "juvmabdq", "rank": 61, "score": 10.638699531555176}, {"content": "Title: Comorbidities and Disparities in Outcomes of COVID-19 Among African American and White Patients Content: Initial surveillance data suggests a disproportionately high number of deaths among Black patients with COVID-19. However, high-risk comorbidities are often over-represented in the Black population, and understanding whether the disparity is entirely secondary to them is essential. We performed a retrospective cohort study using real-time analysis of electronic medical records (EMR) of patients from multiple healthcare organizations in the United States. Our results showed that Black patients with COVID-19 have a significantly higher risk of mortality, hospitalization, and invasive mechanical ventilation compared to White patients. The incremental risk of poor outcomes in Blacks persists despite accounting for a higher prevalence of comorbidities. This may point to the disparities in socioeconomic determinants of health affecting Blacks and the need for an improvement in the care of this vulnerable population.", "qid": 41, "docid": "cuo7qdkj", "rank": 62, "score": 10.634400367736816}, {"content": "Title: Social Equity and COVID\u201019: The Case of African Americans Content: Emerging statistics demonstrate that COVID\u201019 disproportionately affects African Americans. The effects of COVID\u201019 for this population are inextricably linked to areas of systemic oppression and disenfranchisement, which are further exacerbated by COVID\u201019: (1) healthcare inequality; (2) segregation, overall health, and food insecurity; (3) underrepresentation in government and the medical profession; and (4) inequalities in participatory democracy and public engagement. Following a discussion of these issues, this article shares early and preliminary lessons and strategies on how public administration scholars and practitioners can lead in crafting equitable responses to this global pandemic to uplift the African American community. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "yq7enzvm", "rank": 63, "score": 10.566399574279785}, {"content": "Title: Preliminary evaluation of COVID-19 disease outcomes, test capacities and management approaches among African countries. Content: Background: Following the declaration of COVID-19 as a global pandemic and the report of index case in Africa, the number of countries in Africa with confirmed cases of the infection has grown tremendously with disease now being reported in almost all countries on the continent, with the exemption of Lesotho after 75 days. It is therefore necessary to evaluate the disease outcomes among the African countries as the situation unfolds for early identification of best practices for adoption. Methods: In this study, COVID-19 disease outcomes (confirmed cases, deaths and recoveries), testing capacities and disease management approaches among African countries were evaluated. The relationship between COVID-19 infections in African countries and their performance on global resilient indices including the Human Development Index (HDI), performance on Sustainable Development Goals (SDGs) and the Global Risk Index (GRI) were also examined. Data acquired from various standard databases were evaluated over a period of 75 days from the date of reporting the index case. Results: This study has revealed compelling spatial differences in the incidence, deaths and recoveries from COVID-19 among African countries. Egypt, South Africa, Morocco and Algeria were clustered as countries with highest values of COVID-19 disease outcomes on the continent during the 75-day period of observation. The cluster analysis and comparison of countries in terms of percentage recovered cases of confirmed infections revealed that Mauritius, Mauritania, Gambia, Burkina Faso, Madagascar, Togo and Uganda had the highest scores. Comparative analysis of COVID-19 across the world revealed that the parameters were relatively inconsequential in Oceania and Africa continents, while Europe, North America and Asia had significantly higher cases of disease outcomes. For COVID-19 testing capacities, South Africa, Ghana and Egypt are leading in total number of tests carried out. However when the number of tests carried out were related to population number of the countries, Djibouti, Mauritius, Ghana and South Africa are found to be the leading countries. With respect to management of the disease in Africa, all the countries adopted the WHO protocols, personal hygiene, economic palliatives and social distancing measures. Only three countries in Africa (Madagascar, Togo and Burkina Faso) had a state supported initiative to utilise traditional medicines or herbs as alternatives to control COVID-19. Additionally, most of the countries are providing prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study found that no strong relationship currently exists between the global resilient indicators (HDI, SDG and GRI) and COVID-19 cases across Africa. Conclusions: This study has revealed compelling spatial differences in disease outcomes among African countries and also found testing capacities for COVID-19 to be abysmally low in relation to the population. During the 75 days of observation, African countries have recorded significantly low number of deaths associated with COVID-19 and relatively high recovery rates. Countries in Africa with higher rate of recovery from the disease were found to have adopted strict adherence to some of WHO protocol to contain the disease, isolate all those who test positive to the disease and provide prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study recommends that the approaches adopted by the African countries which achieved high recovery rates from COVID-19 should be integrated into healthcare management plans for the disease across the continent even as the situation unfolds.", "qid": 41, "docid": "uw7qt4jd", "rank": 64, "score": 10.55370044708252}, {"content": "Title: National age and coresidence patterns shape COVID-19 vulnerability Content: Based on harmonized census data from 81 countries, we estimate how age and coresidence patterns shape the vulnerability of countries' populations to outbreaks of coronavirus disease 2019 (COVID-19). We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age structures of European and North American countries increase their vulnerability to COVID-related deaths in general. The coresidence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of COVID-19. Southern European countries, which have aged populations and relatively high levels of intergenerational coresidence, are, all else equal, the most vulnerable to outbreaks of COVID-19. In a second step, we estimate to what extent avoiding primary infections for specific age groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational coresidence, such as France, whereas confining younger age groups can have a greater impact in countries with large and intergenerational households, such as Bangladesh.", "qid": 41, "docid": "gypm0p78", "rank": 65, "score": 10.541000366210938}, {"content": "Title: National age and coresidence patterns shape COVID-19 vulnerability. Content: Based on harmonized census data from 81 countries, we estimate how age and coresidence patterns shape the vulnerability of countries' populations to outbreaks of coronavirus disease 2019 (COVID-19). We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age structures of European and North American countries increase their vulnerability to COVID-related deaths in general. The coresidence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of COVID-19. Southern European countries, which have aged populations and relatively high levels of intergenerational coresidence, are, all else equal, the most vulnerable to outbreaks of COVID-19. In a second step, we estimate to what extent avoiding primary infections for specific age groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational coresidence, such as France, whereas confining younger age groups can have a greater impact in countries with large and intergenerational households, such as Bangladesh.", "qid": 41, "docid": "iw4yv6l4", "rank": 66, "score": 10.540999412536621}, {"content": "Title: National age and co-residence patterns shape covid-19 vulnerability Content: Based on harmonized census data from 81 countries, we estimate how age and co-residence patterns shape the vulnerability of countries' populations to outbreaks of covid-19. We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age-structures of European and North American countries increase their vulnerability to covid-related deaths in general. The co-residence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of covid-19. Southern European countries, which have aged populations and relatively high levels of intergenerational co-residence are, all else equal, the most vulnerable to outbreaks of covid-19. In a second step, we estimate to what extent avoiding primary infections for specific age-groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational co-residence such as France, whereas confining younger age groups can have a greater impact in countries with large and inter-generational households such as Bangladesh.", "qid": 41, "docid": "tpxqj2do", "rank": 67, "score": 10.540998458862305}, {"content": "Title: Two Burning Questions on COVID-19: Did shutting down the economy help? Can we (partially) reopen the economy without risking the second wave? Content: As we reach the apex of the COVID-19 pandemic, the most pressing question facing us is: can we even partially reopen the economy without risking a second wave? We first need to understand if shutting down the economy helped. And if it did, is it possible to achieve similar gains in the war against the pandemic while partially opening up the economy? To do so, it is critical to understand the effects of the various interventions that can be put into place and their corresponding health and economic implications. Since many interventions exist, the key challenge facing policy makers is understanding the potential trade-offs between them, and choosing the particular set of interventions that works best for their circumstance. In this memo, we provide an overview of Synthetic Interventions (a natural generalization of Synthetic Control), a data-driven and statistically principled method to perform what-if scenario planning, i.e., for policy makers to understand the trade-offs between different interventions before having to actually enact them. In essence, the method leverages information from different interventions that have already been enacted across the world and fits it to a policy maker's setting of interest, e.g., to estimate the effect of mobility-restricting interventions on the U.S., we use daily death data from countries that enforced severe mobility restrictions to create a\"synthetic low mobility U.S.\"and predict the counterfactual trajectory of the U.S. if it had indeed applied a similar intervention. Using Synthetic Interventions, we find that lifting severe mobility restrictions and only retaining moderate mobility restrictions (at retail and transit locations), seems to effectively flatten the curve. We hope this provides guidance on weighing the trade-offs between the safety of the population, strain on the healthcare system, and impact on the economy.", "qid": 41, "docid": "9j8lr4vx", "rank": 68, "score": 10.528400421142578}, {"content": "Title: Determinants of COVID-19 Vaccine Acceptance in the U.S. Content: Background:The COVID-19 pandemic continues to adversely affect the U.S., which leads globally in total cases and deaths. As COVID-19 vaccines are under development, public health officials and policymakers need to create strategic vaccine-acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths. Methods: Using an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID-19 pandemic, acceptance of a COVID-19 vaccine, and trust in sources of information. These factors were compared across basic demographics. Findings: Of the 672 participants surveyed, 450 (67%) said they would accept a COVID-19 vaccine if it is recommended for them. Males (72%), older adults ([\u2265]55 years; 78%), Asians (81%), and college and/or graduate degree holders (75%) were more likely to accept the vaccine. When comparing reported influenza vaccine uptake to reported acceptance of the COVID-19 vaccine: 1) participants who did not complete high school had a very low influenza vaccine uptake (10%), while 60% of the same group said they would accept the COVID-19 vaccine; 2) unemployed participants reported lower influenza uptake and lower COVID-19 vaccine acceptance when compared to those employed or retired; and, 3) black Americans reported lower influenza vaccine uptake and lower COVID-19 vaccine acceptance than nearly all other racial groups. Lastly, we identified geographic differences with Department of Health and Human Services regions 2 (New York) and 5 (Chicago) reporting less than 50 percent COVID-19 vaccine acceptance. Interpretation: Although our study found a 67% acceptance of a COVID-19 vaccine, there were noticeable demographic and geographical disparities in vaccine acceptance. Before a COVID-19 vaccine is introduced to the U.S., public health officials and policymakers must prioritize effective COVID-19 vaccine-acceptance messaging for all Americans, especially those who are most vulnerable.", "qid": 41, "docid": "p3zjxo1h", "rank": 69, "score": 10.392499923706055}, {"content": "Title: A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine Content: Blacks/African Americans are overrepresented in the number of hospitalizations and deaths from COVID-19 in the United States, which could be explained through differences in the prevalence of existing comorbidities. We performed a disease-disease phenome-wide association study (PheWAS) using data representing 5,698 COVID-19 patients from a large academic medical center, stratified by race. We explore the association of 1,043 pre-occurring conditions with several COVID-19 outcomes: testing positive, hospitalization, ICU admission, and mortality. Obesity, iron deficiency anemia and type II diabetes were associated with susceptibility in the full cohort, while ill-defined descriptions/complications of heart disease and stage III chronic kidney disease were associated among non-Hispanic White (NHW) and non-Hispanic Black/African American (NHAA) patients, respectively. The top phenotype hits in the full, NHW, and NHAA cohorts for hospitalization were acute renal failure, hypertension, and insufficiency/arrest respiratory failure, respectively. Suggestive relationships between respiratory issues and COVID-19-related ICU admission and mortality were observed, while circulatory system diseases showed stronger association in NHAA patients. We were able to replicate some known comorbidities related to COVID-19 outcomes while discovering potentially unknown associations, such as endocrine/metabolic conditions related to hospitalization and mental disorders related to mortality, for future validation. We provide interactive PheWAS visualization for broader exploration.", "qid": 41, "docid": "915x3q19", "rank": 70, "score": 10.378600120544434}, {"content": "Title: Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study Content: Background: We compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada. Methods: We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression. Results: Between 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population. Interpretation: Heterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.", "qid": 41, "docid": "1u2d4m49", "rank": 71, "score": 10.33240032196045}, {"content": "Title: DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: Potential implications for pathogen recognition and disease susceptibility Content: Dendritic cell\u2013specific intracellular adhesion molecule-3\u2013grabbing nonintegrin (DC-SIGN) and DC-SIGNR are C-type lectins that serve both as cell adhesion and pathogen recognition receptors. Because of the essential role of the these molecules in the immune response, the implication of their alleles in human disease states, and the possible genetic variation at these loci among ethnically diverse populations, we undertook a study to analyze the full extent of DC-SIGN and DC-SIGNR polymorphisms in Caucasian Canadian and indigenous African populations. We report several novel nucleotide variants within regulatory 5\u2032- and 3\u2032-untranslated regions of the genes that could affect their transcription and translation. There were significant differences in the distribution of DC-SIGN and DC-SIGNR alleles among African and non-African populations. Finally, our study clearly demonstrates that Africans show greater genetic diversity at these two closely-related immune loci than observed in other major population groups. The differences may reflect evolutionary pressures generated by environmental factors, such as prevalent pathogens in these geographically distinct regions. Further studies will be needed to determine the net impact of DC-SIGN and DC-SIGNR genetic variants on the expression, translation, and function of the proteins and to understand how these functional polymorphisms may affect immune responses or immune escape.", "qid": 41, "docid": "ermr7wlf", "rank": 72, "score": 10.295599937438965}, {"content": "Title: Equitably Sharing the Benefits and Burdens of Research: Covid\u201019 Raises the Stakes Content: One of the central principles of research ethics is that the benefits and burdens of research with human participants should be equitably distributed. This principle has important implications for where research will be conducted, how participants will be recruited, what questions will be investigated, and who will control the distribution of any innovations that result. In the context of Covid\u201019, key issues include providing support to clinical trials in low\u2010 and middle\u2010income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high\u2010risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. If clinical trials are not designed with equity considerations consciously in mind, the response to the pandemic may further exacerbate disparities in health status between population groups.", "qid": 41, "docid": "mob8dbcr", "rank": 73, "score": 10.284500122070312}, {"content": "Title: Equitably Sharing the Benefits and Burdens of Research: Covid-19 Raises the Stakes Content: One of the central principles of research ethics is that the benefits and burdens of research with human participants should be equitably distributed. This principle has important implications for where research will be conducted, how participants will be recruited, what questions will be investigated, and who will control the distribution of any innovations that result. In the context of Covid-19, key issues include providing support to clinical trials in low- and middle-income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high-risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. If clinical trials are not designed with equity considerations consciously in mind, the response to the pandemic may further exacerbate disparities in health status between population groups.", "qid": 41, "docid": "of5dvq44", "rank": 74, "score": 10.284499168395996}, {"content": "Title: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons Content: CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1\u2014the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (\u2212.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also \u2212.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.", "qid": 41, "docid": "peg0m87x", "rank": 75, "score": 10.177800178527832}, {"content": "Title: APA urges HHS to push for partnership to address pandemic Content: Citing the need to provide urgent information on the impact of COVID\u201019 on key populations and produce data to target behavioral health interventions to vulnerable populations, the American Psychological Association (APA) is urging the U.S. Department of Health and Human Services (HHS) to establish within the Centers for Disease Control and Prevention a public\u2010private partnership to address the pandemic.", "qid": 41, "docid": "pgfxpw2d", "rank": 76, "score": 10.175100326538086}, {"content": "Title: Analysis of hospitalized COVID-19 patients in the Mount Sinai Health System using electronic medical records (EMR) reveals important prognostic factors for improved clinical outcomes Content: COVID-19 is a novel threat to human health worldwide. There is an urgent need to understand patient characteristics of having COVID-19 disease and evaluate markers of critical illness and mortality. Objective: To assess association of clinical features on patient outcomes. Design, Setting, and Participants: In this observational case series, patient-level data were extracted from electronic medical records for 28,336 patients tested for SARS-CoV-2 at the Mount Sinai Health System from 2/24/ to 4/15/2020, including 6,158 laboratory-confirmed cases. Exposures: Confirmed COVID-19 diagnosis by RT-PCR assay from nasal swabs. Main Outcomes and Measures: Effects of race on positive test rates and mortality were assessed. Among positive cases admitted to the hospital (N = 3,273), effects of patient demographics, hospital site and unit, social behavior, vital signs, lab results, and disease comorbidities on discharge and death were estimated. Results: Hispanics (29%) and African Americans (25%) had disproportionately high positive case rates relative to population base rates (p<2e-16); however, no differences in mortality rates were observed in the hospital. Outcome differed significantly between hospitals (Gray's T=248.9; p<2e-16), reflecting differences in average baseline age and underlying comorbidities. Significant risk factors for mortality included age (HR=1.05 [95% CI, 1.04-1.06]; p=1.15e-32), oxygen saturation (HR=0.985 [95% CI, 0.982-0.988]; p=1.57e-17), care in ICU areas (HR=1.58 [95% CI, 1.29-1.92]; p=7.81e-6), and elevated creatinine (HR=1.75 [95% CI, 1.47-2.10]; p=7.48e-10), alanine aminotransferase (ALT) (HR=1.002, [95% CI 1.001-1.003]; p=8.86e-5) and body-mass index (BMI) (HR=1.02, [95% CI 1.00-1.03]; p=1.09e-2). Asthma (HR=0.78 [95% CI, 0.62-0.98]; p=0.031) was significantly associated with increased length of hospital stay, but not mortality. Deceased patients were more likely to have elevated markers of inflammation. Baseline age, BMI, oxygen saturation, respiratory rate, white blood cell (WBC) count, creatinine, and ALT were significant prognostic indicators of mortality. Conclusions and Relevance: While race was associated with higher risk of infection, we did not find a racial disparity in inpatient mortality suggesting that outcomes in a single tertiary care health system are comparable across races. We identified clinical features associated with reduced mortality and discharge. These findings could help to identify which COVID-19 patients are at greatest risk and evaluate the impact on survival.", "qid": 41, "docid": "9pn30z0k", "rank": 77, "score": 10.141900062561035}, {"content": "Title: Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection Content: New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.", "qid": 41, "docid": "qm44flh4", "rank": 78, "score": 10.137900352478027}, {"content": "Title: Infoveillance based on Social Sensors to Analyze the impact of Covid19 in South American Population Content: Infoveillance is an application from Infodemiology field with the aim to monitor public health and create public policies. Social sensor is the people providing thought, ideas through electronic communication channels(i.e. Internet). The actual scenario is related to tackle the covid19 impact over the world, many countries have the infrastructure, scientists to help the growth and countries took actions to decrease the impact. South American countries have a different context about Economy, Health and Research, so Infoveillance can be a useful tool to monitor and improve the decisions and be more strategical. The motivation of this work is analyze the capital of Spanish Speakers Countries in South America using a Text Mining Approach with Twitter as data source. The preliminary results helps to understand what happens two weeks ago and opens the analysis from different perspectives i.e. Economics, Social.", "qid": 41, "docid": "3r5vycnr", "rank": 79, "score": 10.136300086975098}, {"content": "Title: Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents Content: The World Health Organization recently announced that pandemic status has been achieved for coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exponential increases in patient numbers have been reported around the world, along with proportional increases in the number of COVID-19-related deaths. The SARS-CoV-2 infection rate in a population is expected to be influenced by social practices, availability of vaccines or prophylactics, and the prevalence of susceptibility genes in the population. Previous work revealed that cellular uptake of SARS-CoV-2 requires Angiotensin Converting Enzyme 2 (ACE-2) and a cellular protease. The spike (S) protein on SARS-CoV-2 binds ACE-2, which functions as an entry receptor. Following receptor binding, transmembrane protease serine 2 (encoded by TMPRSS2) primes the S protein to allow cellular uptake. Therefore, individual expression of TMPRSS2 may be a crucial determinant of SARS-CoV-2 infection susceptibility. Here, we utilized multiple large genome databases, including the GTEx portal, SNP nexus, and Ensembl genome project, to identify gene expression profiles for TMPRSS2 and its important expression quantitative trait loci. Our results show that four variants (rs464397, rs469390, rs2070788 and rs383510) affect expression of TMPRSS2 in lung tissue. The allele frequency of each variant was then assessed in regional populations, including African, American, European, and three Asian cohorts (China, Japan and Taiwan). Interestingly, our data shows that TMPRSS2-upregulating variants are at higher frequencies in European and American populations than in the Asian populations, which implies that these populations might be relatively susceptible to SARS-CoV-2 infection.", "qid": 41, "docid": "9ehm6dwo", "rank": 80, "score": 10.076899528503418}, {"content": "Title: Generalized logistic growth modeling of the COVID-19 outbreak in 29 provinces in China and in the rest of the world Content: The COVID-19 has been successfully contained in China but is spreading all over the world. We calibrate the logistic growth model, the generalized logistic growth model, the generalized Richards model and the generalized growth model to the reported number of infected cases from for the whole of China, 29 provinces in China, and 19 countries and regions that are undergoing major outbreaks. We dissect the development of the epidemics in China and the impact of the drastic control measures both at the aggregate level and within each province. We quantitatively document four phases of the outbreak in China with a detailed analysis on the heterogeneous situations across provinces. The extreme containment measures implemented by China were very effective with some instructive variations across provinces. Borrowing from the experience of China, we made scenario projections on the development of the outbreak in other countries. We identified that Europe and US have passed the inflection point and entered into an after-peak trajectory, which is estimated longer than what a classical Logistic model predicts, in contrast to most provinces in China where the after-peak trajectory is much faster. We expect Europe to have 1.83 million final total confirmed cases (2452 per million population) and US to have 1.26 million final total confirmed cases (3851 per million population). We identified three groups of countries in different level of outbreak progress, and provide informative implications for the current global pandemic.", "qid": 41, "docid": "cjcxd8z5", "rank": 81, "score": 10.049799919128418}, {"content": "Title: Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach Content: BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases Institute", "qid": 41, "docid": "aiah8kkn", "rank": 82, "score": 10.048999786376953}, {"content": "Title: New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown. MAIN BODY: In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19. CONCLUSION: This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.", "qid": 41, "docid": "hvrj71r3", "rank": 83, "score": 10.04010009765625}, {"content": "Title: Trends in childhood cancer mortality--United States, 1990-2004. Content: Cancer is the fourth most common cause of death (after unintentional injury, homicide, and suicide) among persons aged 1-19 years in the United States. Because recent childhood cancer mortality has not been well characterized in terms of temporal, demographic, and geographic trends, CDC analyzed cancer death rates among children (defined as aged 0-14 years) and adolescents (defined as aged 15-19 years) for the period 1990-2004 by sex, age group, race, ethnicity, U.S. Census region, and primary cancer site/leading diagnosis, using the most recent data available from the National Vital Statistics System (NVSS). This report describes the results of that analysis, which indicated that, overall, age-adjusted childhood cancer death rates decreased significantly during 1990-2004 among both sexes, both age groups, all races (except American Indians/Alaska Natives [AI/ANs]), Hispanics, non-Hispanics, and all U.S. Census regions. However, decreases in death rates varied among U.S. Census regions and between Hispanics and non-Hispanics. Eliminating racial/ethnic health disparities is one of the overarching goals of Healthy People 2010. Further research is needed to understand geographic and ethnic disparities in childhood cancer death rates. Moreover, cancer prevention and intervention measures should be designed to reach populations that are underserved and at high risk.", "qid": 41, "docid": "0falsc4z", "rank": 84, "score": 10.034700393676758}, {"content": "Title: How COVID-19\u2019s Disruption of the U.S. Correctional System Provides an Opportunity for Decarceration Content: The COVID-19 pandemic has amplified decades of vulnerabilities, disparities, and injustices within the U.S. correctional system. The spread of the coronavirus poses a particularly serious threat to those that comprise the system, including personnel, attorneys, prisoners, their families and extends into the communities in which facilities are located. These correctional facilities and communities were especially underprepared for the sudden onset of a highly contagious virus, which has resulted in an exceedingly high number of infections among those who work and are held in the facilities. Rampant overcrowding in the U.S. correctional system, an aging population, and a population exhibiting high rates of underlying health conditions are highly likely to exacerbate the spread of this highly contagious virus. This potentially dire set of interrelated circumstances necessitates rapid decarceration measures that effectively balance public safety and public health. Unfortunately, there has been unclear guidance as well as changing and even contradictory information coming from the federal government concerning rapid measures to mitigate the spread of infection to justice system personnel and federal prisoners. In this paper we summarize the federal response and how it has impacted those responsible for implementation. Furthermore, we discuss how systemic deleterious conditions of the U.S. correctional system serve as both accelerants to as well as effects of the pandemic. We end highlighting critical issues relating to early release due to COVID-19 that will necessitate future research.", "qid": 41, "docid": "5i0zxhs1", "rank": 85, "score": 9.965700149536133}, {"content": "Title: Systematic Review of Interventions to Increase Stool Blood Colorectal Cancer Screening in African Americans Content: African Americans experience colorectal cancer (CRC) related disparities compared to other racial groups in the United States. African Americans are frequently diagnosed with CRC at a later stage, screening is underutilized, and mortality rates are highest in this group. This systematic review focused on intervention studies using stool blood CRC screening among African Americans in primary care and community settings. Given wide accessibility, low cost, and ease of dissemination of stool-based CRC screening tests, this review aims to determine effective interventions to improve participation rates. This systematic review included intervention studies published between January 1, 2000 and March 16, 2019. After reviewing an initial search of 650 studies, 11 studies were eventually included in this review. The included studies were studies conducted in community and clinical settings, using both inreach and outreach strategies to increase CRC screening. For each study, an unadjusted odds ratio (OR) for the CRC screening intervention compared to the control arm was calculated based on the data in each study to report effectiveness. The eleven studies together recruited a total of 3334 participants. The five studies using two-arm experimental designs ranged in effectiveness with ORs ranging from 1.1 to 13.0 using interventions such as mailed reminders, patient navigation, and tailored educational materials. Effective strategies to increase stool blood testing included mailed stool blood tests augmented by patient navigation, tailored educational materials, and follow-up calls or mailings to increase trust in the patient-provider relationship. More studies are needed on stool blood testing interventions to determine effectiveness in this population.", "qid": 41, "docid": "8t5y9gqq", "rank": 86, "score": 9.917799949645996}, {"content": "Title: The Expression and Polymorphism of Entry Machinery for COVID-19 in Human: Juxtaposing Population Groups, Gender, and Different Tissues Content: (1) Background: Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21st century. (2) Methods: The host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. (3) Results: Lung, kidney, small intestine, and salivary glands were among the tissues which expressed the entry machinery coding genes Ace2, Tmprss2, CtsB, and CtsL. The genes had no significant expression changes between males and females. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a common pool of rare variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants including S19P, I21T/V, E23K, A25T, K26R, T27A, E35D/K, E37K, Y50F, N51D/S, M62V, N64K, K68E, F72V, E75G, M82I, T92I, Q102P, G220S, H239Q, G326E, E329G, G352V, D355N, H378R, Q388L, P389H, E467K, H505R, R514G/*, and Y515C were of the utmost importance to the viral entry and infection. The variants of S19P, I21T, K26R, T27A, E37K, N51D, N64K, K68E, F72V, M82I, G326E, H378R, Q388L, and P389H also had significant differences in frequencies among the population groups. Most interestingly, the analyses revealed that more than half of the variants can exist in males, i.e., as hemizygous. (4) Conclusions: The rare variants of human ACE2 seem to be one of the determinant factors associated with fitness in the battle against SARS viruses. The hemizygous viral-entry booster variants of ACE2 describe the higher SARS-CoV-2 mortality rate in males. This is also supported by the lack of gender bias for the gene expression profiles of entry machinery. A personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.", "qid": 41, "docid": "jdu2v2ii", "rank": 87, "score": 9.913399696350098}, {"content": "Title: The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States Content: The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups, with high rates of death in African American, Native American, and LatinX communities. While the mechanisms of these disparities are being investigated, they can be conceived as arising from biomedical factors as well as social determinants of health. Minority groups are disproportionately affected by chronic medical conditions and lower access to healthcare that may portend worse COVID-19 outcomes. Furthermore, minority communities are more likely to experience living and working conditions that predispose them to worse outcomes. Underpinning these disparities are long-standing structural and societal factors that the COVID-19 pandemic has exposed. Clinicians can partner with patients and communities to reduce the short-term impact of COVID-19 disparities while advocating for structural change.", "qid": 41, "docid": "u7s67aug", "rank": 88, "score": 9.889699935913086}, {"content": "Title: COVID-19 and the US response: accelerating health inequities Content: Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public\u2019s health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "qid": 41, "docid": "0ctlde8w", "rank": 89, "score": 9.863699913024902}, {"content": "Title: COVID-19 and the US response: accelerating health inequities Content: Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public's health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "qid": 41, "docid": "n3wbuxnv", "rank": 90, "score": 9.863698959350586}, {"content": "Title: Imaging evaluation of COVID-19 in the emergency department Content: PURPOSE: The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. METHODS: Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. RESULTS: A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. CONCLUSION: We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result.", "qid": 41, "docid": "v8cpbqgz", "rank": 91, "score": 9.826899528503418}, {"content": "Title: Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey Content: BACKGROUND: The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area. METHODS: We conducted an online, cross-sectional social media survey from March 14 \u2013 April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S. RESULTS: The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement. CONCLUSION: These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed.", "qid": 41, "docid": "24xxj8q8", "rank": 92, "score": 9.81980037689209}, {"content": "Title: Motor vehicle-related death rates--United States, 1999-2005. Content: In 2005, the most recent year for which data are available, 45,520 deaths in the United States were related to motor vehicles. A Healthy People 2010 objective calls for reducing the rate of deaths related to motor vehicles to 9.2 per 100,000 population from a baseline of 15.6 in 1998. To assess progress toward the Healthy People objective and to examine characteristics of motor vehicle--related death rates, CDC analyzed data from the National Vital Statistics System (NVSS) for the period 1999--2005. This report summarizes the results of that analysis, which determined that, during 1999--2005, although annual age-adjusted motor vehicle--related death rates overall were nearly unchanged (range: 15.2--15.7 per 100,000 population), substantial differences were observed by state, U.S. Census region, sex, race, and age group. Among states, the average annual death rate ranged from 7.9 per 100,000 population in Massachusetts to 31.9 in Mississippi. Among regions, the rate ranged from 9.8 per 100,000 population in the Northeast to 19.5 in the South. The rate for men (21.7 per 100,000 population) was more than double the rate for women (9.4); the rate for American Indians/Alaska Natives (27.2) was nearly twice the rate for whites (15.7) and blacks (15.2), and the rate for persons aged 15--24 years (26.8) was 74% higher than the average annual rate overall (15.4). Additional analysis and research to determine the causes of geographic and demographic variations in motor vehicle--related deaths might result in more effective targeted interventions among the states, regions, and populations at greatest risk.", "qid": 41, "docid": "yjt2g95o", "rank": 93, "score": 9.810199737548828}, {"content": "Title: COVID-19 Deaths: Which Explanatory Variables Matter the Most? Content: As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads around the World, many questions about the disease are being answered; however, many more remain poorly understood. Although the situation is rapidly evolving, with datasets being continually corrected or updated, it is crucial to understand what factors may be driving transmission through different populations. While studies are beginning to highlight specific parameters that may be playing a role, few have attempted to thoroughly estimate the relative importance of these disparate variables that likely include: climate, population demographics, and imposed state interventions. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted density (PWD), some \"stay at home\" metrics, monthly temperature and precipitation, race/ethnicity, and chronic low respiratory death rate, were all statistically significant. Of these, PWD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWD. Our results strongly support the idea that the loosening of \"lock-down\" orders should be tailored to the local PWD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present.", "qid": 41, "docid": "q4jn5h00", "rank": 94, "score": 9.794699668884277}, {"content": "Title: COVID-19 pandemic in the African continent: forecasts of cumulative cases, new infections, and mortality Content: Background: Africa is the last major region to capitulate to the SARS-CoV-2 (COVID-19) pandemic. The first confirmed COVID-19 case in the region was reported on February 14, but what lies ahead in terms of the course and magnitude of infection remains speculative. To the best of our knowledge, no study, using a robust methodology, provides the immediate and long-term trajectory of COVID-19 for the entire region or accounts for its local context. This paper is the first systematic attempt to provide estimates on how many people would contract the virus and how many would die in the coming few months across Africa. Methods: The forecasts on caseloads and incidences are from a co-variate-based instrumental variable regression model. Fatality rates from Italy and China were further applied to generate mortality estimates after adjustments were made for differences in age-structure, health service quality, and living standards between each of the African countries and those of the reference population. We cover all countries that reported a confirmed case as of March 31, 2020. Results: By the end of June, 16,283,085 people will contract COVID-19 (95% CI 718,403 to 98, 358, 799). With a cumulative caseload of 5,413,4517 (95% CI 1,332,953 to 8,489,940) and 906,625 (95% CI 173, 821 to 4,742,917) Northern and Eastern Africa will respectively be the most and least affected sub-regions in the continent. Cumulative COVID-19 cases on June 30, 2020 are expected to reach 2,912, 864 (95% CI 465,028 to 18,286,358) in Southern Africa, 2,787, 913 (95% CI 517, 489 to 15,056,314) in Western Africa, and 1,185,742 (95% CI 229, 111 to 6,138,692) in Central Africa. New infections (incidence) for the month of April are expected to be the highest in Djibouti, 32.8 per 1000 (95% CI 6.25 to 171.77), while Morocco 1045 (95% CI 167 to 6,547) will register the highest number of deaths. Conclusion: Our study shows that countries that are least urbanized and have a low level of socio-economic development, hence least connected to the outside world, are likely to register lower and slower transmissions, at least at the early stage of the epidemic. However, the same set of enabling factors that worked for their benefit are likely to go against them in implementing interventions that have lessened the impact of the disease elsewhere.", "qid": 41, "docid": "atee6lis", "rank": 95, "score": 9.701299667358398}, {"content": "Title: Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19 Content: Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.", "qid": 41, "docid": "4f6h7agt", "rank": 96, "score": 9.682900428771973}, {"content": "Title: Advanced Chronic Venous Insufficiency. Content: INTRODUCTION Intervention for advanced chronic venous insufficiency is considered an appropriate standard of care. However, outcomes vary among patients who present in advanced clinical stages of disease. The main objectives of this study were to determine whether racial disparity exists at initial presentation and response to intervention. METHODS A retrospective database was created to include all radiofrequency ablation procedures performed by a single surgeon from January 14, 2009, through May 25, 2011. Demographics, clinical traits, race, procedure, and outcomes were analyzed. Stepwise model selection reduced candidate baseline factors to a final parsimonious model, which was analyzed using analysis of variance. RESULTS The database consisted of 300 patients with a predominant female (n = 215, 85%) base and 85 (15%) males, with a mean age distribution of 53 years. The mean body mass index was 30.2. Racial distribution revealed Asian (n = 9, 3.3%), Pacific Islander (n = 1, 0.4%), African American (n = 37, 13.6%), and Caucasian (CAU, n = 225, 82.7%). African Americans presented with more advanced clinical stages than the CAU group-C2: African American 21.6%, CAU 36.7%; C4: African American 35%, CAU 24.3%; and C6: African American 35.1%, CAU 7.5%. African Americans demonstrated a higher preoperative venous clinical severity score (VCSS) than their CAU counterparts. Postprocedural decrease in VCSS score was lower in African Americans than their CAU counterparts. CONCLUSION African American patients present with more advanced venous insufficiency than CAUs. Postprocedural analysis reveals not only slower ulcer healing times but also higher ulcer recurrence rates.", "qid": 41, "docid": "bd3bgevq", "rank": 97, "score": 9.675700187683105}, {"content": "Title: Imaging evaluation of COVID-19 in the emergency department Content: PURPOSE: The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. METHODS: Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. RESULTS: A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. CONCLUSION: We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10140-020-01787-0) contains supplementary material, which is available to authorized users.", "qid": 41, "docid": "6we2k9fi", "rank": 98, "score": 9.657400131225586}, {"content": "Title: Black Lives in a Pandemic: Implications of Systemic Injustice for End-of-Life Care Content: In recent months, Covid-19 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long-standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and end-of-life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. In the experience of many African American patients struggling against terminal illness, health care providers have denied them a say in their own medical decision-making. In the midst of the Covid-19 pandemic, African Americans have once again been denied a say with regard to the rationing of scarce medical resources such as ventilators, in that dominant and ostensibly race-neutral algorithms sacrifice black lives. Is there such thing as a \"good\" or \"dignified\" death when African Americans are dying not merely of Covid-19 but of structural racism?", "qid": 41, "docid": "j2lhpz7j", "rank": 99, "score": 9.644700050354004}, {"content": "Title: Black Lives in a Pandemic: Implications of Systemic Injustice for End\u2010of\u2010Life Care Content: In recent months, Covid\u201019 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long\u2010standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and end\u2010of\u2010life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. In the experience of many African American patients struggling against terminal illness, health care providers have denied them a say in their own medical decision\u2010making. In the midst of the Covid\u201019 pandemic, African Americans have once again been denied a say with regard to the rationing of scarce medical resources such as ventilators, in that dominant and ostensibly race\u2010neutral algorithms sacrifice black lives. Is there such thing as a \u201cgood\u201d or \u201cdignified\u201d death when African Americans are dying not merely of Covid\u201019 but of structural racism?", "qid": 41, "docid": "xo1f35jg", "rank": 100, "score": 9.644699096679688}]}
{"query": "Does Vitamin D impact COVID-19 prevention and treatment?", "hits": [{"content": "Title: Does vitamin D deficiency increase the severity of COVID-19? Content: The severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation. A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation. Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections. Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19. Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes. These conditions are reported to carry a higher mortality in COVID-19. If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.", "qid": 42, "docid": "m22h669g", "rank": 1, "score": 13.780200004577637}, {"content": "Title: Does Vitamin D play a role in the management of Covid-19 in Brazil? Content: The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. Based on literature review, we highlight the findings regarding the protective role of vitamin D for infectious diseases of the respiratory system. However, randomized controlled trials are currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of high insolation. Authors recommend ecological, epidemiological and randomized controlled trials studies to verify this hypothesis.", "qid": 42, "docid": "x4ietehr", "rank": 2, "score": 13.504599571228027}, {"content": "Title: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach Content: Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.", "qid": 42, "docid": "8hvve871", "rank": 3, "score": 13.236499786376953}, {"content": "Title: Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence Content: Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[\u2265]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.", "qid": 42, "docid": "4v71xohx", "rank": 4, "score": 12.505499839782715}, {"content": "Title: Letter: does vitamin D have a potential role against COVID\u201019? Authors' reply Content: We thank Kumar et al for their comments on our review article and the letter connected with that by Panarese and Shahini.(1,2) We agree that there is a complicated effect of vitamin D in preventing the severity of COVID\u201019, while this mechanism is not exactly the same as that of influenza.", "qid": 42, "docid": "s7pwtw9j", "rank": 5, "score": 12.345199584960938}, {"content": "Title: What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Content: Several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating COVID-19. Because of their potential to influence immune response, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19. The authors outline the biologic plausibility, applicable clinical data, and potential role of each of these agents.", "qid": 42, "docid": "waujy98e", "rank": 6, "score": 12.285900115966797}, {"content": "Title: Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe Content: Background: SARS-CoV-2 virus causes a very wide range of COVID-19 disease severity in humans: from completely asymptomatic to fatal, and the reasons behind it are often not understood. There is some data that Vitamin D may have protective effect, so authors decided to analyze European country-wide data to determine if Vitamin D levels are associated with COVID-19 population death rate. Methods: To retrieve the Vitamin D levels data, authors analyzed the Vitamin D European population data compiled by 2019 ECTS Statement on Vitamin D Status published in the European Journal of Endocrinology. For the data set to used for analysis, only recently published data, that included general adult population of both genders ages 40-65 or wider, and must have included the prevalence of Vitamin D deficiency. Results: There were 10 countries data sets that fit the criteria and were analyzed. Severe Vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million from COVID-19 and prevalence of severe Vitamin D deficiency shows a strong correlation with r = 0.76, p = 0.01, indicating significant correlation. Correlation remained significant, even after adjusting for age structure of the population. Additionally, over time, correlation strengthened, and r coefficient asymptoticaly increased. Conclusions: Authors recommend universal screening for Vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.", "qid": 42, "docid": "67gsn4sy", "rank": 7, "score": 12.24020004272461}, {"content": "Title: Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation? Content: Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vit D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vit D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.", "qid": 42, "docid": "bpfwcssk", "rank": 8, "score": 11.941699981689453}, {"content": "Title: Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential? Content: Patients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency is a worldwide problem and is extremely prevalent in these patients. Vitamin D, known for its calcemic effects, also has immunomodulatory and anti-infectious actions and can therefore be a possible agent to treat or prevent exacerbations. This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in CF, COPD, and asthma.", "qid": 42, "docid": "edb5546o", "rank": 9, "score": 11.916600227355957}, {"content": "Title: Role of vitamin D in preventing of COVID-19 infection, progression and severity Content: The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p=0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels (75-125nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "qid": 42, "docid": "8ceblnkz", "rank": 10, "score": 11.884499549865723}, {"content": "Title: Role of vitamin D in preventing of COVID-19 infection, progression and severity Content: The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p = 0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels 75-125 nmol/L. In conclusion, there not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "qid": 42, "docid": "uz34fjyp", "rank": 11, "score": 11.884498596191406}, {"content": "Title: Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus. Content: BACKGROUND The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "qid": 42, "docid": "478wbtfb", "rank": 12, "score": 11.786800384521484}, {"content": "Title: Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS: This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS: Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION: Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "qid": 42, "docid": "jk0ysuy4", "rank": 13, "score": 11.786799430847168}, {"content": "Title: Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans? Content: Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.", "qid": 42, "docid": "q0tu1pja", "rank": 14, "score": 11.760299682617188}, {"content": "Title: Possible role of vitamin D in Covid-19 infection in pediatric population Content: PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and \u00df-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "qid": 42, "docid": "46aln4tk", "rank": 15, "score": 11.644499778747559}, {"content": "Title: Possible role of vitamin D in Covid-19 infection in pediatric population Content: PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and \u03b2-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "qid": 42, "docid": "rvwxysvc", "rank": 16, "score": 11.644498825073242}, {"content": "Title: Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Content: Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website.", "qid": 42, "docid": "24m4rh9w", "rank": 17, "score": 11.627799987792969}, {"content": "Title: Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1) Content: BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterised by a \"cytokine storm\" and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "qid": 42, "docid": "8fu7w0be", "rank": 18, "score": 11.55370044708252}, {"content": "Title: Perspective: Vitamin D deficiency and COVID\u201019 severity \u2013 plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1) Content: BACKGROUND: SARS\u2010CoV\u20102 coronavirus infection ranges from asymptomatic through to fatal COVID\u201019 characterised by a \u201ccytokine storm\u201d and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID\u201019 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID\u201019 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID\u201019 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID\u201019 severity but it is all indirect. Community\u2010based placebo\u2010controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID\u201019 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "qid": 42, "docid": "mspxtag1", "rank": 19, "score": 11.553699493408203}, {"content": "Title: Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes Content: We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.", "qid": 42, "docid": "rwh56zhg", "rank": 20, "score": 11.534099578857422}, {"content": "Title: Vitamin D can prevent COVID-19 infection-induced multiple organ damage Content: Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.", "qid": 42, "docid": "yjx6ejrh", "rank": 21, "score": 11.38010025024414}, {"content": "Title: Vitamin D and respiratory infections in infants and toddlers: a nutri-shine perspective Content: There is compelling evidence of a global problem of poor vitamin D status in expecting mothers and postnatal life; and even more critical, is the evidence showing the association of vitamin D deficiency with increased morbidity and mortality risks from respiratory infections. Viral and bacterial pneumonia kills more children than any other illness, accounting for 19 % of all deaths in children less than five years of age worldwide; and under-nutrition, which includes vitamin D insufficiency/deficiency, has been implicated in 53 % of all these deaths. Poor vitamin D status is a result of insufficient sunlight exposure and/or poor dietary intake. Greater understanding of the role of vitamin D deficiency in precipitating lung infections grew from the use of rodent models and observational and intervention studies in infants and toddlers. Vitamin D adequacy is important to maintaining the key protective mechanism of developing lungs since it mediates the synthesis of antimicrobial peptides, the lungs strongest defense against viral and bacterial pathogens. If vitamin D intervention currently under study in several clinical trials is proven successful, then implementation of new fortification practices, revised guidelines for healthy sun exposure and public health programs for vitamin D supplementation of pregnant/lactating women and their infants may be effective strategies to aide in preventing neonates and children under five from developing pneumonia. Globally, there is potential to save more than a million young lives with preventive treatment, a compelling reason why the efficacy of optimizing vitamin D mediated defense against respiratory pathogens in infants and children merits further study.", "qid": 42, "docid": "rqp4huk3", "rank": 22, "score": 11.377799987792969}, {"content": "Title: Can Composite Nutritional Supplement Based on the Current Guidelines Prevent Vitamin and Mineral Deficiency After Weight Loss Surgery? Content: BACKGROUND Nutritional deficiencies occur after weight loss surgery. Despite knowledge of nutritional risk, there is little uniformity of postoperative vitamin and mineral supplementation. The objective of this study was to evaluate a composite supplement based on the clinical practice guidelines proposed in 2008 regarding vitamin and mineral supplementation after Roux-en-Y gastric bypass. The composite included iron (Fe) and calcium as well. METHODS A retrospective chart review of 309 patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) was evaluated for the development of deficiencies in iron and vitamins A, B1, B12, and D. Patients were instructed to take a custom vitamin and mineral supplement that was based on society-approved guidelines. The clinical practice guidelines were modified to include 1600 international units (IU) of vitamin D3 instead of the recommended 800 IU. RESULTS The compliant patients' deficiency rates were significantly lower than those of the noncompliant patients for iron (p = 0.001), vitamin A (p = 0.01), vitamin B12 (p \u2248 0.02), and vitamin D (p < 0.0001). Women's menstrual status did not significantly influence the development of iron deficiency. CONCLUSIONS Use of a composite based on guidelines proposed by the AACE, TOS, and the ASMBS appears to be effective for preventing iron and vitamins A, B1, B12, and D deficiencies in the LRYGB patients during the first postoperative year. Separation of calcium and Fe does not need to be mandatory. Even with simplification, compliance is far from universal.", "qid": 42, "docid": "3q2jju2u", "rank": 23, "score": 11.268600463867188}, {"content": "Title: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality Content: WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.", "qid": 42, "docid": "jak0gx9k", "rank": 24, "score": 11.246700286865234}, {"content": "Title: Avoidance of vitamin D deficiency to slow the COVID-19 pandemic Content: Vitamin D deficiency, which impedes good immune function, is common during winter and spring in regions of high latitude. There is good evidence that vitamin D deficiency contributes to the seasonal increase of virus infections of the respiratory tract, from the common cold to influenza, and now possibly also COVID-19. This communication explores key factors that make it more likely, particularly in combination, that individuals are vitamin D deficient. These factors include old age, obesity, dark skin tone and common genetic variants that impede vitamin D status. Precision nutrition is an approach that aims to consider known personal risk factors and health circumstances to provide more effective nutrition guidance in health and disease. In regard to avoiding vitamin D deficiency, people with excess body fat, a dark skin tone or older age usually need to use a moderately dosed daily vitamin D supplement, particularly those living in a high-latitude region, getting little ultraviolet B exposure due to air pollution or staying mostly indoors. Carriers of the GC (group-specific component) rs4588 AA genotype also are more likely to become deficient. Very high-dosed supplements with more than 4000 IU vitamin D are rarely needed or justified. A state-by-state Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the USA shows a greater disparity in northern states than in southern states. It is conceivable that vitamin D adequacy denies the virus easy footholds and thereby slows spreading of the contagion. This finding should drive home the message that vitamin D supplementation is particularly important for individuals with dark skin tones. Vitamin D deficiency, even for a few months during the winter and spring season, must be rigorously remedied because of its many adverse health impacts that include decreased life expectancy and increased mortality. Slowing the spread of COVID-19 would be an added bonus.", "qid": 42, "docid": "7lb9w9ab", "rank": 25, "score": 11.168499946594238}, {"content": "Title: Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Content: The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D(3) for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40\u201360 ng/mL (100\u2013150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D(3) doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "qid": 42, "docid": "iqe6sdq2", "rank": 26, "score": 11.042799949645996}, {"content": "Title: Myth Busters: Dietary Supplements and COVID-19 Content: News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.", "qid": 42, "docid": "gu5vrd2v", "rank": 27, "score": 11.035699844360352}, {"content": "Title: Myth Busters: Dietary Supplements and COVID-19. Content: News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.", "qid": 42, "docid": "jykb5thv", "rank": 28, "score": 11.035698890686035}, {"content": "Title: The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms Content: There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.", "qid": 42, "docid": "ux844b25", "rank": 29, "score": 11.025799751281738}, {"content": "Title: Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Content: The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "qid": 42, "docid": "9vsi8hfx", "rank": 30, "score": 11.007200241088867}, {"content": "Title: Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37 Content: Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.", "qid": 42, "docid": "wr9hkvd3", "rank": 31, "score": 10.94379997253418}, {"content": "Title: Influence of Colostrum and Vitamins A, D(3), and E on Early Intestinal Colonization of Neonatal Holstein Calves Infected with Mycobacterium avium subsp. paratuberculosis Content: Exposure of neonates to Mycobacterium avium subsp. paratuberculosis (MAP) via infected dams is the primary mode of transmission of Johne\u2019s disease. Little is known about the impacts of feeding colostrum and supplemental vitamins on the gut microbiome in calves exposed to MAP. In the present study, calves were assigned at birth to one of six treatment groups: (1) Colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D(3); (5) CR, vitamin E; (6) CR, vitamins A, D(3), E, with five calves per treatment in a 14-day study. All calves were orally inoculated with MAP on days 1 and 3 of the study. Differences due to vitamin supplementation were not significant but treatment groups CR-A, CR-E, and CR-ADE had higher numbers of MAP-positive tissues overall. Shannon diversity indices demonstrated regional differences in microbial communities, primarily Proteobacteria, Bacteroidetes, and Firmicutes, between the ileum, cecum, and spiral colon of all calves. CD calves exhibited increased richness compared with CR calves in the cecum and spiral colon and harbored increased Proteobacteria and decreased Bacteroidetes in the mucosa compared with the lumen for all three tissues. Overall, supplementation with vitamins did not appear to influence gut microbiome or impact MAP infection. Feeding of colostrum influenced gut microbiome and resulted in fewer incidences of dysbiosis.", "qid": 42, "docid": "60o3anwu", "rank": 32, "score": 10.894800186157227}, {"content": "Title: The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond Content: Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.", "qid": 42, "docid": "dqqrulyx", "rank": 33, "score": 10.847100257873535}, {"content": "Title: Vitamin D(3) and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial Content: BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D(3) supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. METHODS: We randomized 600 students into 4 treatment arms: 1) vitamin D(3) and gargling, 2) placebo and gargling, 3) vitamin D(3) and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D(3) reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI(95):0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI(95):0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D(3) treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI(95):0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log(10) viral copies/mL (mean difference: -0.89, CI(95:) -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI(95):0.53-1.26, p = 0.36). CONCLUSIONS: These results suggest that vitamin D(3) is a promising intervention for the prevention of URTI. Vitamin D(3) significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. TRIAL REGISTRATION: Clinical Trials Registration: NCT01158560.", "qid": 42, "docid": "lobhurai", "rank": 34, "score": 10.802200317382812}, {"content": "Title: The Use of IV vitamin C for patients with COVID-19: a single center observational study. Content: BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has affected almost 2.5 million people worldwide with almost 170 000 deaths reported to date. So far, there is scarce evidence for the current treatment options available for COVID-19. Vitamin C has previously been used for treatment of severe sepsis and septic shock. We reviewed the feasibility of using vitamin C in the setting of COVID-19 in a series of patients. METHODS We sequentially identified a series of patients who were requiring at least 30% of FiO2 or more who received IV vitamin C as part of the COVID-19 treatment and analyzed their demographic and clinical characteristics. We compared inflammatory markers pre and post treatment including D-dimer and ferritin. RESULTS We identified a total of 17 patients who received IV vitamin C for COVID-19. The inpatient mortality rate in this series was 12% with 17.6% rates of intubation and mechanical ventilation. We noted a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration. CONCLUSION The use of IV vitamin C in patients with moderate to severe COVID-19 disease may be feasible.", "qid": 42, "docid": "vbj4ki20", "rank": 35, "score": 10.791999816894531}, {"content": "Title: Effects of an Omega-3 and Vitamin D Supplement on Fatty Acids and Vitamin D Serum Levels in Double-Blinded, Randomized, Controlled Trials in Healthy and Crohn\u2019s Disease Populations Content: Two trials separately measured the bioavailability and impact on inflammation of a supplement taken daily containing 510 mg Docosahexaenoic acid (DHA), 344 mg Eicosapentaenoic acid (EPA), and 1000 IU of vitamin D (25-hydroxyvitamin D; 25(OH)D), for healthy and Crohn\u2019s disease (CD) populations. Both trials were double blinded, randomized, placebo-controlled with cross-over. Participants were randomly allocated to groups A (placebo then supplement) or B (supplement then placebo). Both included a washout. Fatty acid (N-3 PUFAs) and vitamin D serum levels, plasma C-reactive protein (CRP), and stool calprotectin were measured before and after each treatment period. Outcome measures were analyzed using generalized linear mixed models, including terms for treatment, period, and a treatment-by-period interaction. The supplement significantly increased serum levels in healthy and CD groups for EPA (p < 0.001 and p < 0.001, respectively), Docosapentaenoic acid (p < 0.001 and 0.005), DHA (p < 0.001 and 0.006), the omega-3 index (p < 0.001 and 0.001), and (vitamin D (p < 0.001 and 0.027). CRP and calprotectin measures showed no evidence of a treatment effect on inflammation; however, model estimation was imprecise for both outcomes, hence further research is required to elucidate potential inflammation effects. The nutrient supplement increased serum levels of key N-3 PUFAs and vitamin D in both populations, showing the preparation was readily bioavailable.", "qid": 42, "docid": "56dez4ak", "rank": 36, "score": 10.7298002243042}, {"content": "Title: El suplemento con altas dosis de vitamina D podr\u00eda representar una alternativa promisoria para prevenir o tratar la infecci\u00f3n por COVID-19 Content: Resumen Si bien carecemos de suficiente evidencia que justifique suplementar con vitamina D en la prevenci\u00f3n y/o tratamiento de la infecci\u00f3n por COVID-19, a la fecha resulta cada vez m\u00e1s factible que esta hip\u00f3tesis sea v\u00e1lida. Dos mecanismos b\u00e1sicos generales deber\u00edan ser considerados. Uno ser\u00eda la acci\u00f3n anti-infecciosa e inmuno-moduladora que ejerce mejorando las barreras intercelulares por est\u00edmulo de la inmunidad innata, as\u00ed tambi\u00e9n por modulaci\u00f3n de la inmunidad adaptativa. Tambi\u00e9n, la vitamina D reduce la producci\u00f3n de citoquinas inflamatorias como IL-2 e interfer\u00f3n gamma (INF\u03b3). M\u00e1s recientemente se han demostrado m\u00faltiples efectos pleiotr\u00f3picos sobre las acciones de vitamina D a nivel anti-inflamatorio e inmuno-modulador. Esto explica resultados positivos en estudios con influenza, coronavirus y otras infecciones respiratorias. Se ha descripto relaci\u00f3n inversa entre niveles s\u00e9ricos de vitamina D y prevalencia de patolog\u00eda infecciosa respiratoria. De inter\u00e9s, otro abordaje mecan\u00edstico responde a considerar la inhibici\u00f3n del sistema renina-angiotensina-aldosterona, que se exacerba en la infecci\u00f3n por COVID-19 debido a que el virus se une a la enzima ECA2, quedando disponible m\u00e1s angiotensina II para causar da\u00f1o. La vitamina D inhibe mediadores del SRAA -presente en todas las c\u00e9lulas del organismo-, y por inhibir la actividad ECA y aumentar la ECA2, disminuye los niveles de angiotensina II. Presentamos estudios con propuestas de dosis recomendadas de vitamina D y aunque no quede concretada una \u00fanica gu\u00eda, los posibles beneficios son promisorios. Finalmente, el prop\u00f3sito de la presente revisi\u00f3n es compartir esta idea con profesionales de la salud para encender el debate y llamar a la reflexi\u00f3n cr\u00edtica, de modo tal que se pueda contribuir con el emprendimiento de dise\u00f1os cl\u00ednicos adecuados para validar los beneficios de utilizar altas dosis de vitamina D en beneficio de la salud p\u00fablica y sobre todo en tiempos de esta emergencia por COVID-19. Abstract Although we lack enough evidence to justify supplementing with vitamin D in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitamin D reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF\u03b3). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitamin D at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitamin D levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensin II available to cause damage. Vitamin D inhibits mediators of RAAS -present in all cells of the body- and by inhibiting ACE activity and increasing ACE2, it lowers angiotensin II levels. We present studies with proposals for recommended doses of vitamin D, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitamin D for the benefit of public health and especially in times of crisis for COVID-19.", "qid": 42, "docid": "1b7viy5o", "rank": 37, "score": 10.706999778747559}, {"content": "Title: Beneficial role of vitamin D3 in the prevention of certain respiratory diseases. Content: There is evidence of aberrations in the vitamin D-endocrine system in subjects with respiratory diseases. Vitamin D deficiency is highly prevalent in patients with respiratory diseases, and patients who receive vitamin D have significantly larger improvements in inspiratory muscle strength and maximal oxygen uptake. Studies have provided an opportunity to determine which proteins link vitamin D to respiratory pathology, including the major histocompatibility complex class II molecules, vitamin D receptor, vitamin D-binding protein, chromosome P450, Toll-like receptors, poly(ADP-ribose) polymerase-1, and the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on respiratory diseases through cell signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/\u03b2-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D plays a significant role in respiratory diseases. The best form of vitamin D for use in the treatment of respiratory diseases is calcitriol because it is the active metabolite of vitamin D3 and modulates inflammatory cytokine expression. Further investigation of calcitriol in respiratory diseases is needed.", "qid": 42, "docid": "fm5h7vg0", "rank": 38, "score": 10.700799942016602}, {"content": "Title: Vitamin D Deficiency and Acute Lower Respiratory Infections in Children Younger Than 5 Years: Identification and Treatment Content: Abstract Introduction Acute lower respiratory infection (ALRI) is a leading cause of childhood mortality. Research suggests that vitamin D deficiency (VDD) puts children at risk for ALRI. The purpose of this review is to examine ALRI and VDD in children 5 years and younger. Common etiologies, diagnosis, prevention, treatment of ALRI, and recommendations for vitamin D supplementation are summarized. Method Databases were searched for studies investigating VDD and ALRI in children. Independent reviewers assessed the internal validity of the studies. Results Of 18 studies examined, VDD was found to be associated with increased risk or severity of ALRI in 13 studies; associations were not found in 4 studies. In one study it was found that high maternal vitamin D levels was associated with ALRI in infants. Discussion Vitamin D supplementation is a low-cost, low-risk intervention that providers should consider for children, especially those at high risk for ALRI. Practitioners should follow current recommendations when prescribing vitamin D supplementation for infants and children.", "qid": 42, "docid": "ke1l83wc", "rank": 39, "score": 10.63659954071045}, {"content": "Title: Vitamin D deficiency 2.0: an update on the current status worldwide Content: Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L or 20 ng/ml) is associated with unfavorable skeletal outcomes, including fractures and bone loss. A 25(OH)D level of >50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.", "qid": 42, "docid": "pm7ihh9t", "rank": 40, "score": 10.576499938964844}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 42, "docid": "rirzes0m", "rank": 41, "score": 10.434700012207031}, {"content": "Title: Covid-19, cocooning and vitamin d intake requirements Content: The purpose of this report is to clarify what constitutes best practice on vitamin D supplement use, particularly among older adults, who are at highest risk of Covid-19 On Friday 3rd April, three reports were published on how vitamin D may protect against Covid-19 Two reports are aligned with national and international guidelines on vitamin intake requirements for health: one looked at the importance of vitamin D adequacy in protecting children from respiratory illness but included important advice cautioning against high dose vitamin D;the other is from The Irish Longitudinal Study on Ageing (TILDA) that looked at specific \u2019at risk\u2019 groups for vitamin D deficiency in those over 50 years in a representative sample from the 26 counties TILDA provides a strong evidence base for intervening in older adults with supplemental vitamin D (10 \u00b5g to 20 \u00b5g daily) A third report advises that every adult should take high doses of vitamin D (20 \u00b5g to 50 \u00b5g daily) in order to protect against Covid-19 The authors make no mention about other sources of vitamin D in adults This creates confusion at a time when there is widespread fear and anxiety about the Covid-19 pandemic The following provides a review of the evidence and summarises best practice regarding vitamin D nutrition to protect against Covid-19", "qid": 42, "docid": "ipm58ohm", "rank": 42, "score": 10.393799781799316}, {"content": "Title: Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold Content: Purpose: To present a critical evaluation of the current evidence concerning the therapeutic value of vitamin C for the prophylaxis and treatment of the common cold. Data sources: Cochrane, PubMed, Natural Standard, and the National Center for Complementary and Alternative Medicine databases were searched to identify and acquire primary research reports, literature reviews, and secondary analyses related to the clinical objective. Published clinical trials, literature reviews, meta\u2010analyses, and systematic reviews were evaluated for evidence\u2010based practice implications. Conclusions: Vitamin C is frequently used for the treatment and prophylaxis of the common cold; however, no published recommendations were found in a review of the nurse practitioner literature that specifically address the efficacy of vitamin C for the common cold. Our literature review revealed that vitamin C is not effective at preventing the common cold in the general adult population; however, it is effective at preventing colds when consumed regularly by athletes training in subarctic conditions. We also found that regular vitamin C consumption may reduce the duration of cold symptoms in both adults and children, but it does not decrease the severity of cold symptoms. Implications for practice: NPs should counsel their patients that regular vitamin C consumption may decrease the duration of cold symptoms, but does not affect symptom severity or act as a prophylaxis.", "qid": 42, "docid": "29wn8kaw", "rank": 43, "score": 10.384900093078613}, {"content": "Title: Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: \"Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths\" Nutrients 2020, 12(4), 988 Content: There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "qid": 42, "docid": "pt1i1au3", "rank": 44, "score": 10.192500114440918}, {"content": "Title: Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: \u201cEvidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths\u201d Nutrients 2020, 12(4), 988 Content: There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "qid": 42, "docid": "svc2xeh1", "rank": 45, "score": 10.192499160766602}, {"content": "Title: A brief review of interplay between vitamin D and angiotensin\u2010converting enzyme 2: Implications for a potential treatment for COVID\u201019 Content: The novel coronavirus disease 2019 (COVID\u201019) is rapidly expanding and causing many deaths all over the world with the World Health Organization (WHO) declaring a pandemic in March 2020. Current therapeutic options are limited and there is no registered and/or definite treatment or vaccine for this disease or the causative infection, severe acute respiratory coronavirus 2 syndrome (SARS\u2010CoV\u20102). Angiotensin\u2010converting enzyme 2 (ACE2), a part of the renin\u2010angiotensin system (RAS), serves as the major entry point into cells for SARS\u2010CoV\u20102 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat\u2010soluble\u2010vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation. It can induce ACE2/Ang\u2010(1\u20107)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang\u2010(1\u20107) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, targeting the unbalanced RAS and ACE2 down\u2010regulation with vitamin D in SARS\u2010CoV\u20102 infection is a potential therapeutic approach to combat COVID\u201019 and induced ARDS.", "qid": 42, "docid": "qslc2wry", "rank": 46, "score": 10.179699897766113}, {"content": "Title: A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19 Content: The novel coronavirus disease 2019 (COVID-19) is rapidly expanding and causing many deaths all over the world with the World Health Organization (WHO) declaring a pandemic in March 2020. Current therapeutic options are limited and there is no registered and/or definite treatment or vaccine for this disease or the causative infection, severe acute respiratory coronavirus 2 syndrome (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2), a part of the renin-angiotensin system (RAS), serves as the major entry point into cells for SARS-CoV-2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat-soluble-vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation. It can induce ACE2/Ang-(1-7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang-(1-7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, targeting the unbalanced RAS and ACE2 down-regulation with vitamin D in SARS-CoV-2 infection is a potential therapeutic approach to combat COVID-19 and induced ARDS.", "qid": 42, "docid": "vu7lwypg", "rank": 47, "score": 10.179698944091797}, {"content": "Title: Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Vitamin A 25,000 IU daily. Vitamin D 600,000 IU once during study. Vitamin E 300 IU twice daily. Vitamin C is taken four times per day. B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B(2) 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B(6) 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 \u03bcg, folic acid 400 \u03bcg, and cyanocobalamin 5 \u03bcg]. The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI. 2. Severity of pulmonary involvement according to CT scan. 3. Respiratory support (invasive or non-invasive). 4. Percentage of oxygen saturation (SpO2 level). 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-\u03b1. 6. The patient\u2019s body temperature. 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys). 8. Duration of hospitalization. 9. Mortality rate. RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1. Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).", "qid": 42, "docid": "wzxorv0a", "rank": 48, "score": 10.135700225830078}, {"content": "Title: Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics Content: Importance: Vitamin D deficiency increases the incidence of respiratory virus infections. More than 1 billion people worldwide are vitamin D deficient. If vitamin D deficiency is associated to incidence or severity of SARS-CoV-2 infection, a global call could be made for vitamin D supplementation to mitigate the pandemic. Objective: to determine if lower serum 25-hydroxyvitamin D (25(OH)D) levels are correlated to the risk for COVID-19 and its severity as measured by CT Design: single-center observational study Setting: AZ Delta general hospital Participants: 186 consecutive patients with PCR-confirmed SARS-CoV-2 infection hospitalized for COVID-19 from March 1, 2020 to April 7, 2020 Main outcome and measures: comparative analysis of 25(OH)D levels in patients hospitalized for COVID-19 at various radiological stages and a season/age/sex-matched diseased control population Results: we report on 186 SARS-CoV-2 infected patients requiring hospitalization for severe COVID-19: 109 males (median age 68 years, IQR 53-79 years) and 77 females (median age 71 years, IQR 65-74 years). At admission patients were screened by CT to determine temporal changes of COVID-19 lung disease and classified as stage 1 (ground glass opacities), 2 (crazy paving pattern) and 3 (consolidation). At intake, 25(OH)D levels were measured and compared to a season-matched population of 2717 diseased controls, consisting of 999 males (median age 69 years, IQR 53-81 years) and 1718 females (median age 68 years, IQR 43-83 years). Male and female COVID-19 patients combined showed lower median 25(OH)D than controls (18.6 ng/mL, IQR 12.6-25.3, versus 21.5 ng/mL, IQR 13.9-30.8; P=0.0016) and a higher fraction of vitamin D deficiency (58.6% versus 45.2%, P=0.0005). A strong sexual dimorphism was found: female patients had comparable vitamin D status as control females. Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3. Conclusions and relevance: vitamin D deficiency is a possible risk factor for severe SARS-CoV-2 infection in males. Vitamin D supplementation might be an inexpensive, accessible and safe mitigation for the SARS-CoV-2 pandemic.", "qid": 42, "docid": "rpmmadqc", "rank": 49, "score": 10.119600296020508}, {"content": "Title: Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Content: Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.", "qid": 42, "docid": "jvyr7pq4", "rank": 50, "score": 10.107199668884277}, {"content": "Title: Vitamin D and inflammation: Potential implications for severity of Covid-19 Content: Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection Covid-19 infection and mortality data was gathered from the World Health Organisation Results Counter-intuitively, lower latitude and typically \u2018sunny\u2019 countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency These countries have also been experiencing the highest infection and death rates in Europe The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0 046) by Spearman's Rank Correlation Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19 There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19", "qid": 42, "docid": "lo6u1buy", "rank": 51, "score": 10.107198715209961}, {"content": "Title: Effects of fractionated colostrum replacer and vitamins A, D, and E on haptoglobin and clinical health in neonatal Holstein calves challenged with Mycobacterium avium ssp. paratuberculosis Content: Abstract Thirty Holstein calves were obtained from 2 dairy farms in central Iowa at birth and randomly assigned to 1 of 6 treatment groups: (1) colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D3; (5) CR, vitamin E; and (6) CR, vitamins A, D3, E, with 5 calves per treatment in a 14-d study. Calves were fed pasteurized whole milk (CD) or fractionated colostrum replacer (CR) at birth (d 0) and injected with vitamins according to treatment group. From d 1 through d 14 of the study, all calves were fed pasteurized whole milk (PWM) supplemented with vitamins as assigned. All calves were inoculated with Mycobacterium avium ssp. paratuberculosis on d 1 and 3 of age. Calves fed CR acquired IgG1 and haptoglobin in serum within 24 h of birth, whereas CD calves did not. The CR-fed calves were 2.5 times less likely to develop scours, and CR calves supplemented with vitamins D3 and E also demonstrated a decreased incidence of scours. Serum vitamin levels of A, D, and E increased within treatment group by d 7 and 14 of the study. Interestingly, synergistic effects of supplemental vitamins A, D3, and E on serum 25-(OH)-vitamin D were observed at d 7, resulting in higher levels than in calves administered vitamin D only. Further, vitamin D3 deficiency was observed in CD and CR calves fed a basal diet of pasteurized whole milk and no supplemental vitamins. Colonization of tissues with Mycobacterium avium ssp. paratuberculosis was negligible and was not affected by colostrum feeding or vitamin supplementation. Results demonstrated passive transfer of haptoglobin to neonatal calves, and potential health benefits of supplemental vitamins D3 and E to calves fed pasteurized whole milk.", "qid": 42, "docid": "86j5nx7c", "rank": 52, "score": 10.072099685668945}, {"content": "Title: 'Scientific Strabismus' or two related pandemics: coronavirus disease and vitamin D deficiency Content: The WHO has announced the novel coronavirus disease (COVID-19) outbreak to be a global pandemic. The distribution of community outbreaks shows seasonal patterns along certain latitude, temperature and humidity, that is, similar to the behaviour of seasonal viral respiratory tract infections. COVID-19 displays significant spread in northern mid-latitude countries with an average temperature of 5\u00ad11\u00b0C and low humidity. Vitamin D deficiency has also been described as pandemic, especially in Europe. Regardless of age, ethnicity and latitude, recent data showed that 40 % of Europeans are vitamin D deficient (25-hydroxyvitamin D (25(OH)D) levels <50 nmol/l), and 13 % are severely deficient (25(OH)D < 30 nmol/l). A quadratic relationship was found between the prevalences of vitamin D deficiency in most commonly affected countries by COVID-19 and the latitudes. Vitamin D deficiency is more common in the subtropical and mid-latitude countries than the tropical and high-latitude countries. The most commonly affected countries with severe vitamin D deficiency are from the subtropical (Saudi Arabia 46 %; Qatar 46 %; Iran 33\u00b74 %; Chile 26\u00b74 %) and mid-latitude (France 27\u00b73 %; Portugal 21\u00b72 %; Austria 19\u00b73 %) regions. Severe vitamin D deficiency was found to be nearly 0 % in some high-latitude countries (e.g. Norway, Finland, Sweden, Denmark and Netherlands). Accordingly, we would like to call attention to the possible association between severe vitamin D deficiency and mortality pertaining to COVID-19. Given its rare side effects and relatively wide safety, prophylactic vitamin D supplementation and/or food fortification might reasonably serve as a very convenient adjuvant therapy for these two worldwide public health problems alike.", "qid": 42, "docid": "lj4mq31p", "rank": 53, "score": 10.066100120544434}, {"content": "Title: Vitamin D deficiency in patients with diabetes and COVID- 19 infection Content: BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term 'COVID 19' combined with 'Diabetes', 'Vitamin D', 'Extra skeletal effects', 'immunity', 'infection', 'India' from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "qid": 42, "docid": "99zkwrso", "rank": 54, "score": 10.03909969329834}, {"content": "Title: Vitamin D deficiency in patients with diabetes and COVID- 19 infection Content: BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term \u2018COVID 19\u2019 combined with \u2018Diabetes\u2019, \u2018Vitamin D\u2019, \u2018Extra skeletal effects\u2019, \u2018immunity\u2019, \u2018infection\u2019, \u2018India\u2019 from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "qid": 42, "docid": "ktzx5lz6", "rank": 55, "score": 10.039098739624023}, {"content": "Title: Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank Content: Purpose Vitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p=0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p=0.696). Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.", "qid": 42, "docid": "npk92gra", "rank": 56, "score": 10.014699935913086}, {"content": "Title: Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment Content: COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.", "qid": 42, "docid": "o8c1i5c2", "rank": 57, "score": 10.009099960327148}, {"content": "Title: Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson\u2019s Disease Content: While we are still learning more about COVID-19, caused by the novel SARS-CoV-2 virus, finding alternative and already available methods to reduce the risk and severity of the disease is paramount. One such option is vitamin D, in the form of vitamin D(3) (cholecalciferol) supplementation, due to its potential antiviral properties. It has become apparent that older individuals have a greater risk of developing severe COVID-19, and compared to younger adults, the elderly have lower levels of vitamin D due to a variety of biological and behavioral factors. Older adults are also more likely to be diagnosed with Parkinson\u2019s disease (PD), with advanced age being the single greatest risk factor. In addition to its immune-system-modulating effects, it has been suggested that vitamin D supplementation plays a role in slowing PD progression and improving PD-related quality of life. We completed a review of the literature to determine the relationship between vitamin D, PD, and COVID-19. We concluded that the daily supplementation of 2000\u20135000 IU/day of vitamin D(3) in older adults with PD has the potential to slow the progression of PD while also potentially offering additional protection against COVID-19.", "qid": 42, "docid": "wfz010d5", "rank": 58, "score": 9.984800338745117}, {"content": "Title: Vitamin D deficiency and COVID-19 pandemic Content: \u2022 Vitamin D deficiency is very frequent. \u2022 Controlled trials showed that vitamin D decreases acute respiratory infections. \u2022 Despite a lack of direct evidence of an effect of vitamin D on COVID-19 infection. \u2022 Daily vitamin D supplementation with moderate doses is safe and cheap. \u2022 Even a small decrease in COVID-19 infections would easily justify this intervention.", "qid": 42, "docid": "fe7e60dl", "rank": 59, "score": 9.978599548339844}, {"content": "Title: Dietary recommendations during the COVID-19 pandemic Content: Optimal nutrition can improve well-being and might mitigate the risk and morbidity associated with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes nutritional guidelines to support dietary counseling provided by dietitians and health-related professionals. The majority of documents encouraged the consumption of fruits, vegetables, and whole grain foods. Thirty-one percent of the guidelines highlighted the importance of minerals and vitamins such as zinc and vitamins C, A, and D to maintain a well-functioning immune system. Dietary supplementation has not been linked to COVID-19 prevention. However, supplementation with vitamins C and D, as well as with zinc and selenium, was highlighted as potentially beneficial for individuals with, or at risk of, respiratory viral infections or for those in whom nutrient deficiency is detected. There was no convincing evidence that food or food packaging is associated with the transmission of COVID-19, but good hygiene practices for handling and preparing foods were recommended. No changes to breastfeeding recommendations have been made, even in women diagnosed with COVID-19.", "qid": 42, "docid": "wbspn2zm", "rank": 60, "score": 9.956299781799316}, {"content": "Title: Dietary recommendations during the COVID-19 pandemic. Content: Optimal nutrition can improve well-being and might mitigate the risk and morbidity associated with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes nutritional guidelines to support dietary counseling provided by dietitians and health-related professionals. The majority of documents encouraged the consumption of fruits, vegetables, and whole grain foods. Thirty-one percent of the guidelines highlighted the importance of minerals and vitamins such as zinc and vitamins C, A, and D to maintain a well-functioning immune system. Dietary supplementation has not been linked to COVID-19 prevention. However, supplementation with vitamins C and D, as well as with zinc and selenium, was highlighted as potentially beneficial for individuals with, or at risk of, respiratory viral infections or for those in whom nutrient deficiency is detected. There was no convincing evidence that food or food packaging is associated with the transmission of COVID-19, but good hygiene practices for handling and preparing foods were recommended. No changes to breastfeeding recommendations have been made, even in women diagnosed with COVID-19.", "qid": 42, "docid": "zrlqzbss", "rank": 61, "score": 9.956298828125}, {"content": "Title: Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective Content: PURPOSE: The review aims to provide a summary of the current literature regarding common medications prescribed in orthopaedic surgery and their potential implications in COVID-19 patients. METHODS: A systematic review was performed using the PRISMA guidelines. All clinical studies, reviews, consensus and guidelines related to the above medications and COVID-19 were included. RESULTS: A total of 18 articles were included. The use of analgesia, anti-inflammatories, steroids, anticoagulants, antibiotics, vitamin B, vitamin C and vitamin D and their potential impact on COVID-19 patients were reported. CONCLUSION: Eight main recommendations were derived from the review. Firstly, paracetamol remains the first line of analgesia and antipyretic. Secondly, there is no need to avoid NSAIDs for COVID-19 patients. Thirdly, opioids have the potential for immunosuppression in addition to respiratory depression and, therefore, should be prescribed with care in COVID-19 patients. Fourthly, patients with conditions where steroids are proven to be efficacious can continue to receive their steroids; otherwise, systemic steroids are not recommended for COVID-19 patients. Fifthly, orthopaedic surgeons following up on COVID-19 patients who are using steroids should continue to follow them up for possible avascular necrosis. Sixthly, whenever possible, oral anticoagulation should be converted to parental heparin. Seventhly, common orthopaedic antibiotics including penicillin and clindamycin are safe to continue for COVID-19 patients. However, for COVID-19 patients, the antibiotics can potentially be switched to macrolides and tetracyclines if the organisms are sensitive. Lastly, prescription for vitamins B, C and D should continue as per usual clinical practice.", "qid": 42, "docid": "rwiur1wh", "rank": 62, "score": 9.949899673461914}, {"content": "Title: Does vitamin D status impact mortality from SARS-CoV-2 infection? Content:", "qid": 42, "docid": "9itdow8a", "rank": 63, "score": 9.936200141906738}, {"content": "Title: Vitamin D concentrations and COVID-19 infection in UK Biobank Content: Abstract Background and aims COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. Methods UK Biobank recruited 502,624 participants aged 37\u201373 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. Results Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99\u20130.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998\u20131.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68\u20137.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65\u20134.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.", "qid": 42, "docid": "0oxy9b1p", "rank": 64, "score": 9.932000160217285}, {"content": "Title: Vitamin D concentrations and COVID-19 infection in UK Biobank Content: BACKGROUND AND AIMS: COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. METHODS: UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. RESULTS: Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99-0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998-1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68-7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65-4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. CONCLUSIONS: Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.", "qid": 42, "docid": "gitj540h", "rank": 65, "score": 9.931999206542969}, {"content": "Title: Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Content: Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "qid": 42, "docid": "5rfxis6f", "rank": 66, "score": 9.900400161743164}, {"content": "Title: Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Content: Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "qid": 42, "docid": "cb2j9i53", "rank": 67, "score": 9.900399208068848}, {"content": "Title: Double COVID-19 Confirmed Case Fatality Rate in Countries with High Elderly Female Vitamin D Deficiency Prevalence Content: A number of clues point to a possible role of vitamin D in fighting COVID-19: a reduction in case growth speed with solar zenith angle, higher fatality rate in black people, lower fatality rate in populations that spend more time outdoors. Yet a direct demonstration that vitamin D deficiency is associated with COVID-19 fatalities has remained elusive. We show here in a comparison of 32 countries that countries with high prevalence of vitamin D deficiency among elderly females show a confirmed case fatality rate twice as high as those with low prevalence. We then show that this effect cannot be explained by differences in life expectancy between countries. A mechanistic role for vitamin D in the severity of COVID-19 is proposed.", "qid": 42, "docid": "jdrhu6l1", "rank": 68, "score": 9.807999610900879}, {"content": "Title: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D Content: BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the \"worldometer\" web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r\u00e2\u0080\u00af=\u00e2\u0080\u00af.40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.", "qid": 42, "docid": "jy45c2pk", "rank": 69, "score": 9.802499771118164}, {"content": "Title: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D Content: BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the \u201cworldometer\u201d web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = .40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.", "qid": 42, "docid": "l8bsoqbx", "rank": 70, "score": 9.802498817443848}, {"content": "Title: Letter: does vitamin D have a potential role against COVID-19? Content:", "qid": 42, "docid": "at0tm7tp", "rank": 71, "score": 9.734800338745117}, {"content": "Title: Letter: does vitamin D have a potential role against COVID\u201019? Content:", "qid": 42, "docid": "lcqn2fk1", "rank": 72, "score": 9.7347993850708}, {"content": "Title: Vitamin D and Immunity in Infants and Children Content: The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.", "qid": 42, "docid": "an2xdbcz", "rank": 73, "score": 9.718600273132324}, {"content": "Title: Letter: does vitamin D have a potential role against COVID-19? Authors' reply Content:", "qid": 42, "docid": "ay562jqu", "rank": 74, "score": 9.698200225830078}, {"content": "Title: 1,25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis. Content: Multiple sclerosis (MS) is an incurable autoimmune neurodegenerative disease. Environmental factors may be key to MS prevention and treatment. MS prevalence and severity decrease with increasing sunlight exposure and vitamin D(3) supplies, supporting our hypothesis that the sunlight-dependent hormone, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3) ), inhibits autoimmune T-cell responses in MS. Moreover, 1,25-(OH)(2) D(3) inhibits and reverses experimental autoimmune encephalomyelitis (EAE), an MS model. Here, we investigated whether 1,25-(OH)(2) D(3) inhibits EAE via the vitamin D receptor (VDR) in T lymphocytes. Using bone marrow chimeric mice with a disrupted VDR only in radio-sensitive hematopoietic cells or radio-resistant non-hematopoietic cells, we found that hematopoietic cell VDR function was necessary for 1,25-(OH)(2) D(3) to inhibit EAE. Furthermore, conditional targeting experiments showed that VDR function in T cells was necessary. Neither 1,25-(OH)(2) D(3) nor T-cell-specific VDR targeting influenced CD4(+) Foxp3(+) T-cell proportions in the periphery or the CNS in these studies. These data support a model wherein 1,25-(OH)(2) D(3) acts directly on pathogenic CD4(+) T cells to inhibit EAE.", "qid": 42, "docid": "phv4oymq", "rank": 75, "score": 9.657400131225586}, {"content": "Title: Responsibility for vitamin D supplementation of elderly care home residents in England: falling through the gap between medicine and food Content: Abstract Introduction: Vitamin D supplements are recommended for elderly care home residents with little sunlight exposure. However, their use in care homes is limited and vitamin D deficiency in residents is widespread. This study aimed to understand perceived responsibility for the vitamin D status of residents and the determinants of current practice around supplementation. Methods: Thirteen semi-structured interviews were conducted with key informants in two areas of Southern England including care home managers, general practitioners (GPs) and public health professionals. Interviews were audio recorded and transcribed verbatim. Results: Inductive thematic analysis identified four themes: medical framing; professional and sector boundaries; awareness of national guidance; and ethical and practical issues. Vitamin D supplements were not routinely given to residents, and most participants, including the GPs, believed the vitamin D status of residents was the responsibility of the GP. Care home managers felt unable to make decisions about vitamin D and vulnerable to suggestions of wrongdoing in administering over-the-counter vitamin tablets. This results in vitamin D requiring prescription by medical professionals and few care home residents receiving vitamin D supplements. Conclusion: The medical framing of vitamin D supplements in care homes is a practical barrier to residents receiving them and is out of step with public health recommendations. Vitamin D levels in care home residents could be improved through universal supplementation. This requires a paradigm shift so that vitamin D is understood as a protective nutrient as well as a medicine, and a public health as well as a medical responsibility. The failure to ensure vitamin D adequacy of residents may emerge as a factor in the spread and severity of COVID-19 in care homes and gives increased urgency to addressing this issue.", "qid": 42, "docid": "7fibv18p", "rank": 76, "score": 9.646100044250488}, {"content": "Title: Local expression profiles of vitamin D-related genes in airways of COPD patients. Content: Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.", "qid": 42, "docid": "sx19tm6v", "rank": 77, "score": 9.639800071716309}, {"content": "Title: Spurious Correlation? A review of the relationship between Vitamin D and Covid-19 infection and mortality Content: The study reviews the evidence presented in a recent study linking vitamin D levels and Covid-19 infection and mortality. It was argued that correlation alone may not be useful in establishing a relationship between vitamin D levels and Covid-19 infections and mortality. Appropriate controls need to be included for improved understanding of the relationship. We proposed life expectancy as a potential control. Including this control in a regression model, we find that vitamin D levels are not a statistically significant predictor of Covid-19 infections or mortality. Life expectancy, on the other hand, was found to be statistically significant predictor of infections and mortality at country level.", "qid": 42, "docid": "hevwcofh", "rank": 78, "score": 9.627699851989746}, {"content": "Title: Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol. Content: BACKGROUND Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. TRIAL REGISTRATION This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.", "qid": 42, "docid": "4qxh85c0", "rank": 79, "score": 9.618900299072266}, {"content": "Title: Letter: low population mortality from COVID\u201019 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity Content: The recent editorial by Rhodes et al considered latitude and mentioned one mechanism that vitamin D is important in regulating and suppressing the inflammatory response of cytokines of respiratory epithelial cells and macrophages to various pathogens, including respiratory viruses and preventing cytokine storm and the subsequent acute respiratory distress syndrome (RDS) (1).", "qid": 42, "docid": "07z1deqg", "rank": 80, "score": 9.548299789428711}, {"content": "Title: Counter-regulatory 'Renin-Angiotensin' System-based Candidate Drugs to Treat COVID-19 Diseases in SARS-CoV-2-infected patients Content: SARS-CoV-2 / COVID-19 and the 'Renin-Angiotensin' System The ubiquitous 'Renin-Angiotensin' system (RAS), also referred to as 'Renin-Angiotensin-Aldosterone' system, plays a crucial physiological role in humans as being a key regulator of renal, cardiovascular and innate immune functions [1, 2]. It appears to work in tandem with vitamin D, a secosteroid pro-hormone which reportedly acts as a negative regulatory factor of the RAS [3-6]. A dysfunction (e.g. over-reactivity) of RAS, together with hypovitaminosis D, is likely associated with some of the various renal, cardiac, vascular and immune outcomes that might be observed in COVID-19 patients, including the cytokine storm (i.e. unopposed hyperactive immune reaction generating both pro-inflammatory and anti-inflammatory cytokines) and consequent lethal acute respiratory distress syndrome [1, 7]. Recently, SARS-CoV-2 [8, 9], the causative agent of COVID-19, has been described to interfere with the RAS [2] by interacting -via its spike (S) glycoprotein- with the metallopeptidase Angiotensin-Converting Enzyme 2 (ACE2) receptor [9, 10] that is expressed at the surface of epithelial cells from blood vessels, lung, kidney (renal tubules), intestine, and heart, as well as on cerebral neurons and immune monocytes/macrophages [11-13]. The main SARS-CoV-2-related COVID-19 symptoms/diseases reported hitherto are hypertension, atherosclerosis, thrombosis (coagulopathy), diarrhea, glaucoma, anosmia, ageusia, skin lesions (dermatitis), autoimmune inflammation of the central nervous system, and damages to various organs such as the lung, heart, kidney, and testicle [1, 2, 14]. All these diffuse COVID-19 disorders are likely linked to an over-reaction of RAS in SARS-CoV-2-infected persons. Such a RAS imbalance would be also favored by hypovitaminosis D [2-7, 11]. Since RAS appears to be central in COVID-19 symptoms/diseases, selective targeting of key component(s) of this system might be appropriate to treat RAS-dependent disorders. COVID-19 Disorders: 'Renin-Angiotensin' System (RAS) & Counter-regulatory RAS In the RAS pathway [1, 15], Renin (kidney) cleaves Angiotensinogen (liver) to give Angiotensin I (i.e. peptide DRVYIHPFHL). The latter is cleaved by the Angiotensin-Converting Enzyme (ACE) to produce Angiotensin II (i.e. peptide DRVYIHPF), which is the substrate of ACE2 (SARS-CoV-2 receptor) and key player of the RAS. The cellular targets of Angiotensin II are the vasoconstrictor type 1 (AT1R) and vasodilatator type 2 (AT2R) Angiotensin II receptors (AT1R is expressed at the surface of monocytes/macrophages and T-cells indicating that RAS acts on innate immunity in host). When cleaved by ACE2, Angiotensin II gives Angiotensin 1-7 (i.e. peptide DRVYIHP), targeting the vasodilatator proto-oncogene Mas receptor (MasR). Angiotensin 1-7 can be further transformed to Alamandine (i.e. peptide ARVYIHP) by an aspartate decarboxylase. Alamandine would bind to the vasodilatator Mas-related G protein-coupled receptor member D (MRGD) thus promoting most of the Angiotensin 1-7-like effects. Angiotensin II can produce Angiotensin A (i.e. peptide ARVYIHPF) via an aspartate decarboxylase, and Alamandine via an additional ACE2 cleavage. ACE2 can also cleave Angiotensin I to form Angiotensin 1-9 (i.e. peptide DRVYIHPFH), which targets AT2R. In the RAS pathway were finally evidenced the related Angiotensin III (i.e. peptide RVYIHPF) and Angiotensin IV (i.e. peptide VYIHPF) variants targeting the AT1R and vasodilatator AT4R, respectively. From the known molecular functioning of the RAS, Angiotensins I and II (aside Angiotensin III) are playing central roles in the activity of RAS and associated pathologies, including COVID-19 [2, 10]. Interestingly, it appears that a 'counter-regulatory' RAS does exist to modulate system homeostasis; it relies on Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A, and Angiotensin IV, which are targeting the MasR, AT2R, MRGD, ACE2 and AT4R vasodilatator receptors, respectively. These peptides were found to exhibit cardioprotective, vasoactive (anti-hypertensive), anti-hypertrophic and/or anti-inflammatory potentials [15]. Such naturally-produced molecules of the RAS are expected to counteract the SARS-CoV-2-induced over-activation of RAS and reverse, to some extent, the associated COVID-19 diseases. CONCLUDING REMARKS A recent report suggests that RAS inhibitors may act on the severity of viral infection and mortality of COVID-19 patients [14]. Whether or not RAS blockers would be beneficial to COVID-19 cases is still controversial. The RAS inhibitors likely prevent the cytokine storm as RAS is reported to control the release of pro-inflammatory cytokines [1, 7]. It appears that COVID-19 disorders of SARS-CoV-2-infected humans depend on the RAS over-reacted by the (ACE2-dependent) viral infection and vitamin D deficiency. The track for a possible COVID-19 treatment would be to target RAS using specific candidate chemotherapeutic drugs. The proposed molecules are (so far) ACE inhibitors (to prevent the production of Angiotensin II from Angiotensin I), and blockers/antagonists of AT1R such as Losartan and derivatives. Recombinant ACE2 (under clinical trials) is also considered as a decoy for the recognition and competitive binding to the spike (S) glycoprotein of SARS-CoV-2 [9, 10]. We support the use of natural candidate peptide drugs that belong to the 'counter-regulatory' RAS, i.e. Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A and/or Angiotensin IV to treat COVID-19 disorders. The targeted receptors would thus be MasR, AT2R, MRGD, ACE2 and AT4R. The authors wish to thank Bonabes De Roug\u00e9 MD for fruitful discussions.", "qid": 42, "docid": "1f52iqjg", "rank": 81, "score": 9.484800338745117}, {"content": "Title: Counter-regulatory 'Renin-Angiotensin' System-based Candidate Drugs to Treat COVID-19 Diseases in SARS-CoV-2-infected patients. Content: SARS-CoV-2 / COVID-19 and the 'Renin-Angiotensin' System The ubiquitous 'Renin-Angiotensin' system (RAS), also referred to as 'Renin-Angiotensin-Aldosterone' system, plays a crucial physiological role in humans as being a key regulator of renal, cardiovascular and innate immune functions [1, 2]. It appears to work in tandem with vitamin D, a secosteroid pro-hormone which reportedly acts as a negative regulatory factor of the RAS [3-6]. A dysfunction (e.g. over-reactivity) of RAS, together with hypovitaminosis D, is likely associated with some of the various renal, cardiac, vascular and immune outcomes that might be observed in COVID-19 patients, including the cytokine storm (i.e. unopposed hyperactive immune reaction generating both pro-inflammatory and anti-inflammatory cytokines) and consequent lethal acute respiratory distress syndrome [1, 7]. Recently, SARS-CoV-2 [8, 9], the causative agent of COVID-19, has been described to interfere with the RAS [2] by interacting -via its spike (S) glycoprotein- with the metallopeptidase Angiotensin-Converting Enzyme 2 (ACE2) receptor [9, 10] that is expressed at the surface of epithelial cells from blood vessels, lung, kidney (renal tubules), intestine, and heart, as well as on cerebral neurons and immune monocytes/macrophages [11-13]. The main SARS-CoV-2-related COVID-19 symptoms/diseases reported hitherto are hypertension, atherosclerosis, thrombosis (coagulopathy), diarrhea, glaucoma, anosmia, ageusia, skin lesions (dermatitis), autoimmune inflammation of the central nervous system, and damages to various organs such as the lung, heart, kidney, and testicle [1, 2, 14]. All these diffuse COVID-19 disorders are likely linked to an over-reaction of RAS in SARS-CoV-2-infected persons. Such a RAS imbalance would be also favored by hypovitaminosis D [2-7, 11]. Since RAS appears to be central in COVID-19 symptoms/diseases, selective targeting of key component(s) of this system might be appropriate to treat RAS-dependent disorders. COVID-19 Disorders: 'Renin-Angiotensin' System (RAS) & Counter-regulatory RAS In the RAS pathway [1, 15], Renin (kidney) cleaves Angiotensinogen (liver) to give Angiotensin I (i.e. peptide DRVYIHPFHL). The latter is cleaved by the Angiotensin-Converting Enzyme (ACE) to produce Angiotensin II (i.e. peptide DRVYIHPF), which is the substrate of ACE2 (SARS-CoV-2 receptor) and key player of the RAS. The cellular targets of Angiotensin II are the vasoconstrictor type 1 (AT1R) and vasodilatator type 2 (AT2R) Angiotensin II receptors (AT1R is expressed at the surface of monocytes/macrophages and T-cells indicating that RAS acts on innate immunity in host). When cleaved by ACE2, Angiotensin II gives Angiotensin 1-7 (i.e. peptide DRVYIHP), targeting the vasodilatator proto-oncogene Mas receptor (MasR). Angiotensin 1-7 can be further transformed to Alamandine (i.e. peptide ARVYIHP) by an aspartate decarboxylase. Alamandine would bind to the vasodilatator Mas-related G protein-coupled receptor member D (MRGD) thus promoting most of the Angiotensin 1-7-like effects. Angiotensin II can produce Angiotensin A (i.e. peptide ARVYIHPF) via an aspartate decarboxylase, and Alamandine via an additional ACE2 cleavage. ACE2 can also cleave Angiotensin I to form Angiotensin 1-9 (i.e. peptide DRVYIHPFH), which targets AT2R. In the RAS pathway were finally evidenced the related Angiotensin III (i.e. peptide RVYIHPF) and Angiotensin IV (i.e. peptide VYIHPF) variants targeting the AT1R and vasodilatator AT4R, respectively. From the known molecular functioning of the RAS, Angiotensins I and II (aside Angiotensin III) are playing central roles in the activity of RAS and associated pathologies, including COVID-19 [2, 10]. Interestingly, it appears that a 'counter-regulatory' RAS does exist to modulate system homeostasis; it relies on Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A, and Angiotensin IV, which are targeting the MasR, AT2R, MRGD, ACE2 and AT4R vasodilatator receptors, respectively. These peptides were found to exhibit cardioprotective, vasoactive (anti-hypertensive), anti-hypertrophic and/or anti-inflammatory potentials [15]. Such naturally-produced molecules of the RAS are expected to counteract the SARS-CoV-2-induced over-activation of RAS and reverse, to some extent, the associated COVID-19 diseases. CONCLUDING REMARKS A recent report suggests that RAS inhibitors may act on the severity of viral infection and mortality of COVID-19 patients [14]. Whether or not RAS blockers would be beneficial to COVID-19 cases is still controversial. The RAS inhibitors likely prevent the cytokine storm as RAS is reported to control the release of pro-inflammatory cytokines [1, 7]. It appears that COVID-19 disorders of SARS-CoV-2-infected humans depend on the RAS over-reacted by the (ACE2-dependent) viral infection and vitamin D deficiency. The track for a possible COVID-19 treatment would be to target RAS using specific candidate chemotherapeutic drugs. The proposed molecules are (so far) ACE inhibitors (to prevent the production of Angiotensin II from Angiotensin I), and blockers/antagonists of AT1R such as Losartan and derivatives. Recombinant ACE2 (under clinical trials) is also considered as a decoy for the recognition and competitive binding to the spike (S) glycoprotein of SARS-CoV-2 [9, 10]. We support the use of natural candidate peptide drugs that belong to the 'counter-regulatory' RAS, i.e. Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A and/or Angiotensin IV to treat COVID-19 disorders. The targeted receptors would thus be MasR, AT2R, MRGD, ACE2 and AT4R. The authors wish to thank Bonabes De Roug\u00e9 MD for fruitful discussions.", "qid": 42, "docid": "dubxmtfv", "rank": 82, "score": 9.4847993850708}, {"content": "Title: Modulation of the Immune Response to Respiratory Viruses by Vitamin D Content: Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.", "qid": 42, "docid": "tyabf12r", "rank": 83, "score": 9.464699745178223}, {"content": "Title: Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? Content: There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.", "qid": 42, "docid": "eu7m99a3", "rank": 84, "score": 9.437999725341797}, {"content": "Title: Letter: low population mortality from COVID\u201019 in countries south of latitude 35\u00b0 North supports vitamin D as a factor determining severity\u2014authors\u2019 reply Content: We thank Dr Mansur for his interest in our editorial in which we highlighted the association between northern latitude and increased COVID-19 mortality1 and for his helpful comments about the potential importance of vitamin D effects on cathelicidin and on the renin-angiotensin system, which could be important in protecting against severe COVID-19.2 Vitamin D is a secosteroid hormone, derived like cortisol and sex hormones from cholesterol, so not surprisingly it has a broad range of actions reflecting the several hundred or more genes that are vitamin D-responsive.3,4.", "qid": 42, "docid": "3m8ekphy", "rank": 85, "score": 9.433199882507324}, {"content": "Title: Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease. Content: In sickle cell disease, respiratory infection and asthma may lead to respiratory complications that are a leading cause of morbidity and mortality. Vitamin D has anti-infective and immunomodulatory effects that may decrease the risk for respiratory infections, asthma, and acute chest syndrome. We conducted a randomized double-blind active-controlled clinical trial to determine whether monthly oral vitamin D3 can reduce the rate of respiratory events in children with sickle cell disease. Seventy sickle cell subjects, ages 3-20 years, with baseline records of respiratory events over 1 year before randomization, underwent screening. Sixty-two subjects with 25-hydroxyvitamin D levels of 5-60 ng/mL were randomly assigned to oral vitamin D3 (100 000 IU or 12 000 IU, n = 31 each) under observed administration once monthly for 2 years. The primary outcome was the annual rate of respiratory events (respiratory infection, asthma exacerbation, or acute chest syndrome) ascertained by the use of a validated questionnaire administered biweekly. Analysis included 62 children (mean age of 9.9 years, 52% female, and predominantly with homozygous HbS disease [87%]) with mean baseline 25-hydroxyvitamin D of 14.3 ng/mL. The annual rates of respiratory events at baseline and intervention years 1 and 2 were 4.34 \u00b1 0.35, 4.28 \u00b1 0.36, and 1.49 \u00b1 0.37 (high dose) and 3.91 \u00b1 0.35, 3.34 \u00b1 0.37, and 1.54 \u00b1 0.37 (standard dose), respectively. In pediatric patients with sickle cell disease, 2-year monthly oral vitamin D3 was associated with a >50% reduction in the rate of respiratory illness during the second year (P = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at www.clinicaltrials.gov as #NCT01443728.", "qid": 42, "docid": "58va9ae8", "rank": 86, "score": 9.379899978637695}, {"content": "Title: Reviews of Science for Science Librarians: Vitamins and Trace Elements that May Be Preventive or Ameliorating in This Age of Contagion Content: Prompted by COVID-19, many laypersons now seek information on nutritional support to ward off or help shorten the effects of serious infectious diseases, and are attracted to practices and substances that lack a serious scientific basis. This paper scanned peer-reviewed medical literature to prove a concept: That diets or supplements rich in some vitamins or minerals may indeed be important in managing threats to health caused by a variety of infectious diseases in the past and compares these findings to the current recommendations of the Academy of Nutrition and Dietetics and to research by Zhang and Liu, two China-based pioneers in countering COVID-19. Vitamins A, D, and zinc, are common to both groups and are well supported in the literature. Vitamin C is also a common denominator but has a mixed record of efficacy in dealing with prior infectious outbreaks. Iron has support and do some other vitamins and trace elements. Health science librarians should emphasize that while experts can disagree on particular micronutrients they tend to agree that decisions on protective or curative supplements or diets or should have some basis in fact.", "qid": 42, "docid": "5uo2bxiv", "rank": 87, "score": 9.36240005493164}, {"content": "Title: The impact of vitamin D food fortification and health outcomes in children: a systematic review and meta-regression. Content: OBJECTIVE Vitamin D (vitD) deficiency is a global childhood health problem. Food fortification is a promising strategy to curb vitD deficiency. We aimed to assess the effectiveness of utilizing vitD fortification in staple foods to improve 25hydroxyvitamin D (25(OH)D) concentration and to reduce the prevalence of vitD deficiency among healthy children. METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of vitD fortified food products compared to no fortification among healthy children aged 1-18 years old. We searched Medline, Embase, Global Health, and Cochrane (CENTRAL) databases from database inception until May 2019. Independently, six reviewers in pairs screened titles and abstracts, assessed the full text for eligibility, and performed data extraction and quality assessment. The primary outcome is the impact of fortification on 25(OH)D concentration. The secondary outcomes included the impact of fortification on the prevalence of vitD deficiency, school performance, cognitive function, school absences, infection rate, hospital admission length, and compliance with fortified food product consumption. RESULTS We identified 2229 articles. After assessing eligibility, 20 RCTs met the inclusion criteria. The eligible RCTs assessed the fortification of milk, cereal, juice, bread, yogurt, and cheese compared with no fortification. All RCTs, except for three, had a low risk of bias. Food fortification improved 25(OH)D concentration by a mean difference (MD) of 15.51 nmol/L (95% confidence interval (CI) 6.28, 24.74; I2 = 99%), which resulted in a mean increase of 3 nmol/l for every 100 IU of vitD, when adjusted for baseline 25(OH)D concentration and country latitude. Additionally, the prevalence of vitD deficiency decreased by a risk ratio of 0.53 (95% CI 0.41, 0.69; I2 = 95%), and cognitive function improved by a MD of 1.22 intelligence quotient (IQ) points (95% CI 0.65, 1.79; I2 = 0%). The overall evidence quality was high. CONCLUSION VitD food fortification is an effective way to improve 25(OH)D concentration, prevent vitD deficiency, and improve IQ levels. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017057631.", "qid": 42, "docid": "v2w72a70", "rank": 88, "score": 9.344200134277344}, {"content": "Title: Vitamin D3 in High-Quality Cow Milk: An Italian Case Study Content: The quality-labeling category of high-quality (HQ) milk defined by the Italian legislation must comply with specific requirements concerning rigorous breeder management, hygienic controls, fat and protein content, bacterial load, somatic cells, lactic acid content, and non-denatured soluble serum proteins. However, there is no specification for the vitamin D content of HQ milk. Moreover, the data on the vitamin D content of this milk category are very scarce. In the present study, the content of vitamin D3 was evaluated in HQ raw and pasteurized cow milk obtained from Italian cowsheds and supermarkets. The vitamin D3 content varied from not detected (less than 1 \u00b5g L(\u22121)) to 17.0 \u00b1 2.0 \u00b5g L(\u22121) milk and was not related to the milk fat content. These results represent a case study including a significant although not exhaustive part of the contemporary Italian market of HQ milk. It was shown for the first time that HQ raw milk does not necessarily contain more vitamin D3, even though non-expert consumers likely to buy milk labeled as HQ could expect it. The vitamin D3 content in HQ pasteurized whole milk should be reported on the label of the milk package as a best practice of consumer information policy.", "qid": 42, "docid": "mq1zwpt7", "rank": 89, "score": 9.319000244140625}, {"content": "Title: The link between Vitamin D and Covid-19: distinguishing facts from fiction. Content: Vitamin D is produced in the skin under the influence of UVB-light from the sun or obtained via the diet by eating fatty fish, enriched dairy products or supplements. Vitamin D is known to support a healthy bone and severe deficiency may lead to osteomalacia or the rickets, which still occur in poor areas of the world. In addition, vitamin D support key functions in many organs, including the brain, muscle and the immune systems (Holick, 2007). In fact, the vitamin D receptor (VDR) is expressed in most cell types and may activate somewhere between 200-500 genes, many related to the immune system.", "qid": 42, "docid": "n2ku9n0d", "rank": 90, "score": 9.306900024414062}, {"content": "Title: The link between Vitamin D and Covid-19: distinguishing facts from fiction Content: Vitamin D is produced in the skin under the influence of UVB-light from the sun or obtained via the diet by eating fatty fish, enriched dairy products or supplements. Vitamin D is known to support a healthy bone and severe deficiency may lead to osteomalacia or the rickets, which still occur in poor areas of the world. In addition, vitamin D support key functions in many organs, including the brain, muscle and the immune systems (Holick, 2007). In fact, the vitamin D receptor (VDR) is expressed in most cell types and may activate somewhere between 200-500 genes, many related to the immune system.", "qid": 42, "docid": "py0fjygs", "rank": 91, "score": 9.306899070739746}, {"content": "Title: Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Content: BACKGROUND Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. METHODS PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. RESULTS Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels \u226525 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). CONCLUSIONS Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. TRIAL REGISTRATION NUMBER CRD42014013953.", "qid": 42, "docid": "7tej2b9l", "rank": 92, "score": 9.293899536132812}, {"content": "Title: Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis. Content: INTRODUCTION Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function. METHODS AND ANALYSIS A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (\u226512 months) pain and physical function. Secondary outcomes will include medium-term (\u22656 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest. ETHICS AND DISSEMINATION Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations. PROSPERO REGISTRATION NUMBER CRD42018107740.", "qid": 42, "docid": "9dnyog5i", "rank": 93, "score": 9.289400100708008}, {"content": "Title: Enhancing immunity in viral infections, with special emphasis on COVID-19: A review Content: BACKGROUND AND AIMS: Balanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluate evidence from previous clinical trials that studied nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summarise our observations. METHODS: A systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed\u00ae, Web of Science\u00ae and SciVerse Scopus\u00ae. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included. RESULTS: A total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may also have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population. CONCLUSIONS: We summaries possible benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19.", "qid": 42, "docid": "m16by8h6", "rank": 94, "score": 9.284899711608887}, {"content": "Title: Enhancing immunity in viral infections, with special emphasis on COVID-19: A review Content: Abstract Background and aims Balanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluated evidence from previous clinical trials that evaluated nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summaries our observations. Methods A systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed\u00ae, Web of Science\u00ae and SciVerse Scopus\u00ae. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included. Results total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population. Conclusions We summaries possible benefits of some vitamins, trace elements, nutraceuticals and and probiotics. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19", "qid": 42, "docid": "wmdcxmq2", "rank": 95, "score": 9.28489875793457}, {"content": "Title: Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer\u2014Implications for Pathogenesis and Therapy Content: Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1\u03b1,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.", "qid": 42, "docid": "2qg1z13s", "rank": 96, "score": 9.263500213623047}, {"content": "Title: Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma.", "qid": 42, "docid": "ajla989m", "rank": 97, "score": 9.240799903869629}, {"content": "Title: Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide. Content: Vitamin D deficiency is associated with immune dysregulation, increased vulnerability to infections, depression, and suicidal behavior. One mediator of vitamin D-dependent immune regulation and antimicrobial defense is the cathelicidin antimicrobial peptide (LL-37), encoded by the cathelicidin-related antimicrobial peptide (CRAMP) gene. We compared the mRNA expression of the CRAMP gene, the vitamin D receptor (VDR) gene, as well as the CYP27B1 and CYP24A1 genes (involved in vitamin D metabolism) in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) between depressed individuals who died by suicide (n = 15) and matched (age, gender, and post-mortem interval) non-psychiatric controls (n = 15). Gene expression was measured through qRT-PCR with TaqMan\u00ae primers and probes, with GAPDH and \u03b2-actin genes as endogenous controls. Statistical analyses included t-tests and Pearson correlations. CRAMP mRNA expression was downregulated and VDR mRNA expression was upregulated in both dlPFC and ACC in suicides relative to controls, with no significant differences in expression of CYP24A1 and CYP27B1. To our knowledge, this is the first study on brain cathelicidin expression in the human brain in relationship to suicide. Increased VDR and decreased CRAMP expression are consistent with previously reported associations between vitamin D deficiency, immune dysregulation, and suicidal behavior, and should lead to future studies uncovering novel interactive targets for suicide prevention.", "qid": 42, "docid": "dueignot", "rank": 98, "score": 9.139300346374512}, {"content": "Title: Greater risk of severe COVID-19 in non-White ethnicities is not explained by cardiometabolic, socioeconomic, or behavioural factors, or by 25(OH)-vitamin D status: study of 1,326 cases from the UK Biobank Content: Background We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and non-White ethnicities is explained by cardiometabolic, socio-economic, or behavioural factors. Methods We studied 4,510 UK Biobank participants tested for COVID-19 (positive, n=1,326). Multivariate logistic regression models including age, sex, and ethnicity were used to test whether addition of: 1)cardiometabolic factors (diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking, BMI); 2)25(OH)-vitamin D; 3)poor diet; 4)Townsend deprivation score; 5)housing (home type, overcrowding); or 6)behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. Results There was over-representation of men and non-White ethnicities in the COVID-19 positive group. Non-Whites had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and flats/apartments. Male sex, non-White ethnicity, higher BMI, Townsend deprivation score, and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. Conclusions Sex and ethnicity differential pattern of COVID-19 is not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels, or socio-economic factors. Investigation of alternative biological pathways and different genetic susceptibilities is warranted.", "qid": 42, "docid": "qi6w0sew", "rank": 99, "score": 9.134099960327148}, {"content": "Title: COVID-19: is there a role for immunonutrition, particularly in the over 65s? Content: In late December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei, China, resulting in the potentially fatal COVID-19. It went on to be officially recognised as a pandemic by the World Health Organisation on 11 March 2020. While many public health strategies have evolved, there has been little mention of the immune system and how this could be strengthened to help protect against viral infections such as SARS-CoV-2. The present paper evaluates the current evidence base relating to immunonutrition, with a particular focus on respiratory viruses. Within the nutrition sector a promising body of evidence studying inter-relationships between certain nutrients and immune competence already exists. This could potentially be an important player in helping the body to deal with the coronavirus, especially among elders. Evidence for vitamins C, D and zinc and their roles in preventing pneumonia and respiratory infections (vitamins C and D) and reinforcing immunity (zinc) appears to look particularly promising. Ongoing research within this important field is urgently needed.", "qid": 42, "docid": "479wkesk", "rank": 100, "score": 9.100099563598633}]}
{"query": "How has the COVID-19 pandemic impacted violence in society, including violent crimes?", "hits": [{"content": "Title: Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic Content: OBJECTIVES: To investigate the effect of the COVID-19 pandemic on the frequency of various crime types (property, violent, and mischief) in Vancouver, Canada. METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.", "qid": 43, "docid": "ssv1arr1", "rank": 1, "score": 19.93120002746582}, {"content": "Title: The Impact of Green Space on Violent Crime in Urban Environments: An Evidence Synthesis. Content: Can the presence of green space in urban environments reduce the frequency of violent crime? To ascertain the evidence on this topic, we conducted an in-depth literature review using the PRISMA checklist. The search parameters included US articles written in English and published since 2000. More than 30,000 potential paper titles were identified and ultimately, 45 papers were selected for inclusion. Green spaces typically comprised tree cover, parks and ground cover. Criminal behaviors typically included murder, assault, and theft. The majority of the research reviewed involved quantitative methods (e.g., comparison of green space area to crime data). We extracted multiple mechanisms from the literature that may account for the impact of green space on crime including social interaction and recreation, community perception, biophilic stress reduction, climate modulation, and spaces expressing territorial definition. Recommendations are made for future research, such as meta-analysis of existing data and the development of grounded theory through qualitative data-gathering methods. By providing evidence that access to nature has a mitigating impact on violence in urban settings, city governments and communities are empowered to support these interventions.", "qid": 43, "docid": "8ywevius", "rank": 2, "score": 19.06100082397461}, {"content": "Title: Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis Content: Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "qid": 43, "docid": "po2c65nb", "rank": 3, "score": 17.87470054626465}, {"content": "Title: Impacts of California Proposition 47 on Crime in Santa Monica, CA Content: We examine crime patterns in Santa Monica, California before and after passage of Proposition 47, a 2014 initiative that reclassified some non-violent felonies to misdemeanors. We also study how the 2016 opening of four new light rail stations, and how more community-based policing starting in late 2018, impacted crime. A series of statistical analyses are performed on reclassified (larceny, fraud, possession of narcotics, forgery, receiving/possessing stolen property) and non-reclassified crimes by probing publicly available databases from 2006 to 2019. We compare data before and after passage of Proposition 47, city-wide and within eight neighborhoods. Similar analyses are conducted within a 450 meter radius of the new transit stations. Reports of monthly reclassified crimes increased city-wide by approximately 15% after enactment of Proposition 47, with a significant drop observed in late 2018. Downtown exhibited the largest overall surge. The reported incidence of larceny intensified throughout the city. Two new train stations, including Downtown, reported significant crime increases in their vicinity after service began. While the number of reported reclassified crimes increased after passage of Proposition 47, those not affected by the new law decreased or stayed constant, suggesting that Proposition 47 strongly impacted crime in Santa Monica. Reported crimes decreased in late 2018 concurrent with the adoption of new policing measures that enhanced outreach and patrolling. These findings may be relevant to law enforcement and policy-makers. Follow-up studies needed to confirm long-term trends may be affected by the COVID-19 pandemic that drastically changed societal conditions.", "qid": 43, "docid": "gd0v5vfg", "rank": 4, "score": 16.986600875854492}, {"content": "Title: Has COVID-19 Changed Crime? Crime Rates in the United States during the Pandemic Content: In response to the COVID-19 pandemic, state-level governments across the United States issued mandatory stay-at-home orders around the end of March 2020. Though intended to stop the spread of the COVID-19 virus, the lockdowns have had sweeping impacts on life in ways which were not originally planned. This study\u2019s purpose is to investigate the extent to which governmental responses to COVID-19 have impacted crime rates in the U.S. Compared to the pre-pandemic year of 2019, crime \u2013 as measured by calls for service to law enforcement \u2013 has decreased markedly. However, there are multiple indications that the crime drop is being driven by decreases in minor offenses which are typically committed in peer groups. At the same time, serious crimes which are generally not committed with co-offenders (namely homicide and intimate partner violence) have either remained constant or increased. As such, the crime drop appears to be hiding a very disturbing trend where homicides remain unchanged and intimate partner batteries are increasing. Since many offenders would presumably be committing less serious crimes in a non-pandemic world, we raise attention to the possibility that mandatory lockdown orders may have taken minor offenders and placed them into situations where there is rampant opportunity for intimate partner violence, serious batteries, and homicides. While crime in the U.S. appears to be down overall, this good news should not blind us to a troubling co-occurring reality \u2013 a reality that paints a dim picture of unintended consequences to public health and criminal justice finances as a result of COVID-19 lockdowns.", "qid": 43, "docid": "daxggfj5", "rank": 5, "score": 16.771699905395508}, {"content": "Title: Crime, Justice & the COVID-19 Pandemic: Toward a National Research Agenda Content: The novel corona virus COVID-19 has become a worldwide public health pandemic that has induced anomic conditions impacting daily routines. COVID-19 response measures specifically alter regular schedules and both restrict and expand opportunities for various types of crime while presenting unprecedented challenges for the criminal justice system. For criminologists and criminal justice scientists, the virus also presents natural experiment conditions allowing for real-world theory tests and observation of the relative effectiveness of practice and policy options under weighty conditions. Toward synthesizing scientific discourse and forthcoming empirical work, we suggest the benefits of a COVID-19 crime and justice research program and offer some anchoring concepts. Contagion, containment measures (social distancing, facemasks, shelter-in-place, economic shutdown, virtual work and schooling, banned group gatherings), and social ordinance compliance (voluntary or enforced) posture a conceptual framework from which to align research on crime, justice, and victimization during the virus. After observing crime trends and justice system challenges, we suggest how the pandemic presents opportunities for review of various criminal justice, especially incarceration, policies. System change is a recurring theme across this special issue of the American Journal of Criminal Justice that features twenty additional contributions from a wide range of authoritative crime and justice scholars. These articles on traditional crime during the virus, virus specific hate crime and domestic violence, and the challenges posed by COVID-19 to law enforcement, the courts, and corrections will hopefully provide initial commentary toward deeper inquiry.", "qid": 43, "docid": "7eksp1sj", "rank": 6, "score": 16.43470001220703}, {"content": "Title: Crime Rates in a Pandemic: the Largest Criminological Experiment in History Content: The COVID-19 pandemic of 2020 has impacted the world in ways not seen in generations. Initial evidence suggests one of the effects is crime rates, which appear to have fallen drastically in many communities around the world. We argue that the principal reason for the change is the government ordered stay-at-home orders, which impacted the routine activities of entire populations. Because these orders impacted countries, states, and communities at different times and in different ways, a naturally occurring, quasi-randomized control experiment has unfolded, allowing the testing of criminological theories as never before. Using new and traditional data sources made available as a result of the pandemic criminologists are equipped to study crime in society as never before. We encourage researchers to study specific types of crime, in a temporal fashion (following the stay-at-home orders), and placed-based. The results will reveal not only why, where, when, and to what extent crime changed, but also how to influence future crime reduction.", "qid": 43, "docid": "lcmkribq", "rank": 7, "score": 15.623700141906738}, {"content": "Title: When Stay-at-Home Orders Leave Victims Unsafe at Home: Exploring the Risk and Consequences of Intimate Partner Violence during the COVID-19 Pandemic Content: The novel coronavirus pandemic (hereafter COVID-19) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. This includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter IPV). Most importantly, the COVID-19 pandemic, and its impact on the risk of IPV is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. This review paper explores the potential short- and long-term implications of COVID-19 on the risk of IPV, highlighting some of the most recent preliminary data. The economic impact of the COVID-19 pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. Victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. The paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children.", "qid": 43, "docid": "ekajojon", "rank": 8, "score": 15.335800170898438}, {"content": "Title: Cyber Security in the Age of COVID-19: A Timeline and Analysis of Cyber-Crime and Cyber-Attacks during the Pandemic Content: The COVID-19 pandemic was a remarkable unprecedented event which altered the lives of billions of citizens globally resulting in what became commonly referred to as the new-normal in terms of societal norms and the way we live and work. Aside from the extraordinary impact on society and business as a whole, the pandemic generated a set of unique cyber-crime related circumstances which also affected society and business. The increased anxiety caused by the pandemic heightened the likelihood of cyber-attacks succeeding corresponding with an increase in the number and range of cyber-attacks. This paper analyses the COVID-19 pandemic from a cyber-crime perspective and highlights the range of cyber-attacks experienced globally during the pandemic. Cyber-attacks are analysed and considered within the context of key global events to reveal the modus-operandi of cyber-attack campaigns. The analysis shows how following what appeared to be large gaps between the initial outbreak of the pandemic in China and the first COVID-19 related cyber-attack, attacks steadily became much more prevalent to the point that on some days, 3 or 4 unique cyber-attacks were being reported. The analysis proceeds to utilise the UK as a case study to demonstrate how cyber-criminals leveraged key events and governmental announcements to carefully craft and design cyber-crime campaigns.", "qid": 43, "docid": "j0qperwz", "rank": 9, "score": 15.170100212097168}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence. Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 43, "docid": "1h5a4bit", "rank": 10, "score": 14.453200340270996}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 43, "docid": "clt4l6wz", "rank": 11, "score": 14.45319938659668}, {"content": "Title: Family violence and COVID\u201019: Increased vulnerability and reduced options for support Content: Family violence refers to threatening or other violent behaviour within families that may be physical, sexual, psychological, or economic, and can include child abuse and intimate partner violence (Peterman et al. 2020, van Gelder et al. 2020). Family violence during pandemics is associated with a range of factors including economic stress, disaster-related instability, increased exposure to exploitative relationships, and reduced options for support (Peterman et al. 2020). Due to the social isolation measures implemented across the globe to help reduce the spread of COVID-19, people living in volatile situations of family violence are restricted to their homes. Social isolation exacerbates personal and collective vulnerabilities while limiting accessible and familiar support options (van Gelder et al. 2020). In many countries, including Australia, we have already seen an increase in demand for domestic violence services and reports of increased risk for children not attending schools (Duncan, 2020); a pattern similar to previous episodes of social isolation associated with epidemics and pandemics (Boddy, Young & O'Leary 2020).", "qid": 43, "docid": "4jjuwc9r", "rank": 12, "score": 13.76140022277832}, {"content": "Title: Exploring the Effect of 2019-nCoV Containment Policies on Crime: The Case of Los Angeles Content: The global spread of 2019-nCoV, a new virus belonging to the coronavirus family, forced national and local governments to apply different sets of measures aimed at containing its outbreak. Los Angeles has been one of the first cities in the United States to declare the state of emergency on March 4th, progressively issuing stronger policies involving--among the others--social distancing, the prohibition of crowded private and public gatherings and closure of leisure premises. These interventions highly disrupt and modify daily activities and habits, urban mobility and micro-level interactions between citizens. One of the many social phenomena that could be influenced by such measures is crime. Exploiting public data on crime in Los Angeles, and relying on routine activity and pattern theories of crime, this work investigates whether and how new coronavirus containment policies have an impact on crime trends in a metropolis using Bayesian structural time-series (BSTS) models. The article specifically focuses on nine urban crime categories, daily monitored from January 1st 2017 to March 28th 2020. The analyses have been updated bi-weekly (up to March 16\\ts{th} and up to March 28\\ts{th} 2020) to dynamically assess the short-term effects of mild and hard interventions to shed light on how crime adapts to such structural modification of the environment. The results show that overall crime in Las Angeles is significantly decreasing, as well as robbery, shoplifting, theft and battery. No significant effect has been found for stolen vehicle, burglary, assault with deadly weapon, intimate partner violence and homicide. In the last section of this article, policy implications are also discussed.", "qid": 43, "docid": "0rdq6g0b", "rank": 13, "score": 13.691499710083008}, {"content": "Title: Estimating the impact of violent events on transmission in Ebola virus disease outbreak, Democratic Republic of the Congo, 2018\u20132019 Content: INTRODUCTION: As of April 2019, the current Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) is occurring in a longstanding conflict zone and has become the second largest EVD outbreak in history. It is suspected that after violent events occur, EVD transmission will increase; however, empirical studies to understand the impact of violence on transmission are lacking. Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak. METHODS: We collected daily EVD case counts from DRC Ministry of Health. A time-varying indicator of recent violence in each health zone was derived from events documented in the WHO situation reports. We used the Wallinga-Teunis technique to estimate the reproduction number R for each case by day per zone in the 2018\u20132019 outbreak. We fit an exponentially decaying curve to estimates of R overall and by health zone, for comparison to past outbreaks. RESULTS: As of 16 April 2019, the mean overall R for the entire outbreak was 1.11. We found evidence of an increase in the estimated transmission rates in health zones with recently reported violent events versus those without (p = 0.008). The average R was estimated as between 0.61 and 0.86 in regions not affected by recent violent events, and between 1.01 and 1.07 in zones affected by violent events within the last 21 days, leading to an increase in R between 0.17 and 0.53. Within zones with recent violent events, the mean estimated quenching rate was lower than for all past outbreaks except the 2013\u20132016 West African outbreak. CONCLUSION: The difference in the estimated transmission rates between zones affected by recent violent events suggests that violent events are contributing to increased transmission and the ongoing nature of this outbreak.", "qid": 43, "docid": "tydil7d7", "rank": 14, "score": 13.590200424194336}, {"content": "Title: Special Ambulatory Gynecologic Considerations in the Era of COVID-19 and Implications for Future Practice. Content: The COVID-19 pandemic has altered medical practice in unprecedented ways. While much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain impacts of COVID-19 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care as well. In this article we review important ambulatory gynecologic topics including safety and metal health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible for how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns; threaten continued access to contraception and abortion services; impact prepregnancy planning; interrupt routine screening for breast and cervical cancer; increase risk of sexually-transmitted infection acquisition and decrease access to treatment; and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertion can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasound and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually-transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. While routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papilloma virus self-samples using new cervical cancer screening guidelines that can be expanded in light of the pandemic situation. While the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to attempt to improve health equity.", "qid": 43, "docid": "hlymyzcq", "rank": 15, "score": 13.262999534606934}, {"content": "Title: The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine. Content: Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "qid": 43, "docid": "miem1poh", "rank": 16, "score": 12.672599792480469}, {"content": "Title: The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine Content: Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "qid": 43, "docid": "onxosato", "rank": 17, "score": 12.672598838806152}, {"content": "Title: Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment Content: The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue \u201cstay-at-home\u201d orders to contain the virus\u2019s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory\u2019s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.", "qid": 43, "docid": "gjdza9bh", "rank": 18, "score": 12.437899589538574}, {"content": "Title: Can Homeopathy, a Particularly Mild Therapeutic Approach, Survive and Grow in a World of Violence? Content: This short treatise addresses a philosophical question concerning the place of homeopathy in our modern world. The question raised is whether a therapeutic system as peaceful, mild, and non-violent as homeopathy can survive and grow within a society that often displays the opposite characteristics.Much of contemporary society is more interested in fast and impressive cures, even if these may also bring side effects; whereas homeopathy can offer solutions with a personalized approach that requires long hours of case study by the homeopath to find the correct personal remedy that aims to bring about positive results, which the therapy can produce in deep chronic diseases.The conclusion drawn is that homeopathy does not readily fit within a modern and violent society that prefers quick and invasive solutions to its clinical problems.", "qid": 43, "docid": "nidfrd6o", "rank": 19, "score": 12.38640022277832}, {"content": "Title: JAACAP's Role in Advancing the Science of Pediatric Mental Health and Promoting the Care of Youth and Families During the COVID-19 Pandemic Content: As we pen these words, the COVID-19 pandemic is having profound impacts on human society. Based on decades of research, we know that the accompanying illness,1 death,2 social isolation,3,4 and malnutrition5 will have deep and lasting impacts on our children and adolescents, their families, and the communities in which they develop. The pandemic is exposing, with terrible clarity, the disparities in human society-racism,6 poverty,7,8 domestic violence,9,10 and child maltreatment and neglect11-and tragically will likely amplify the negative impacts that each has on child development and mental health.", "qid": 43, "docid": "77dtxxd4", "rank": 20, "score": 12.080599784851074}, {"content": "Title: Human Rights during COVID-19 pandemic. The issue of Female Genital Mutilations Content: Abstract While SARS-CoV-2 has infected millions and claimed more than 250,000 lives, experts are warning that the impact of other diseases neglected due to the pandemic may be just as significant in the months and years to come. Specifically, when health systems are overwhelmed, and people refrain from visiting health facilities due to movement restrictions or fears about illness exposure, both direct mortality and indirect mortality from preventable and treatable conditions increase.1-3 Female genital mutilation (FGM), also named female genital cutting, is acknowledged as a violation of human rights of women.4 The United Nations Sustainable Development Goals called for the elimination of the practice by 2030.5 FGM is referred to as any procedure involving the alteration or excision of external female genitalia without medical indication,6 and 3 million women in the world are estimated to be at risk of undergoing this procedure annually.6 It is a major public health problem in several countries in Africa and Middle East,6,7 being almost universal in seven African countries (prevalence >85%).6 A report from UNICEF highlighted how this practice is still being widely carried out in 29 countries in Africa and in Middle East, despite the fact that at least 24 of these countries have legislation or some form of decrees against FGM.8 However, some evident progress is ongoing: under the new FGM amendment to the criminal law in Sudan that was approved very recently (22 April 2020), anyone who performs FGM either inside a medical establishment or elsewhere faces three years' imprisonment and fine. 9 Studies conducted in different settings have clearly showed an adverse effect of FGM on psychological, sexual and reproductive health unfavourable outcomes. 10 This includes posttraumatic stress disorder,11 dyspareunia and genitourinary complications. Adverse obstetric outcomes, such as increased risk for caesarean delivery, episiotomy and postpartum haemorrhage, are also more frequent.12 Scar tissue, especially in women with FGM type III (infibulation) can result in obstructed labour or obstetric trauma.13 It is known that in situations of conflicts and disaster, gender inequality, gender-based violence and violation of human rights are likely to increase, as protection and health system are disrupted, leaving acts of violence unpunished and condoned by the societies. This applies to health emergencies as well, including the current COVID-19 pandemic. FGM, early marriage and violence against women and girls are life-threatening, health and human rights challenge, due to the inequal relations, and patriarchal rules.14 Survivors are left no choice or right of determination over their bodies, physical, and sexual and reproductive health. Estimates provided by Avenir Health, Johns Hopkins University (USA) and Victoria University (Australia) predict that significant levels of lockdown-related disruption over 6 months may cause significant delays in programmes to end female genital mutilation, potentially leading to around 2 million more cases of FGM over the next decade than would otherwise have occurred.15 These striking figures become even more daunting when compounded with the expected additional 31 million cases of gender-based violence and the 13 million more child marriages over the next 10 years.15 Support to continued access to reproductive health care services and protection of the rights and dignity of all women and girls remains even more critical in contexts such as the current pandemic. To do so, preparedness and response plans must incorporate and integrate Female Genital Mutilation in Gender-Based Violence, and Sexual and Reproductive Health Programmes, including in community awareness initiatives and activities, thus ensuring risk mitigation as well as remote and mobile case management.", "qid": 43, "docid": "ve9fm15i", "rank": 21, "score": 11.90719985961914}, {"content": "Title: From Fear to Hate: How the Covid-19 Pandemic Sparks Racial Animus in the United States Content: We estimate the effect of the Coronavirus (Covid-19) pandemic on racial animus, as measured by Google searches and Twitter posts including a commonly used anti-Asian racial slur. Our empirical strategy exploits the plausibly exogenous variation in the timing of the first Covid-19 diagnosis across regions in the United States. We find that the first local diagnosis leads to an immediate increase in racist Google searches and Twitter posts, with the latter mainly coming from existing Twitter users posting the slur for the first time. This increase could indicate a rise in future hate crimes, as we document a strong correlation between the use of the slur and anti-Asian hate crimes using historic data. Moreover, we find that the rise in the animosity is directed at Asians rather than other minority groups and is stronger on days when the connection between the disease and Asians is more salient, as proxied by President Trump's tweets mentioning China and Covid-19 at the same time. In contrast, the negative economic impact of the pandemic plays little role in the initial increase in racial animus. Our results suggest that de-emphasizing the connection between the disease and a particular racial group can be effective in curbing current and future racial animus.", "qid": 43, "docid": "6z7oxc2j", "rank": 22, "score": 11.692999839782715}, {"content": "Title: Novel Coronavirus (COVID-19): Violence, Reproductive Rights and Related Health Risks for Women, Opportunities for Practice Innovation Content: While the novel coronavirus (COVID-19) has broad health implications across the globe, being overlooked in response and policy debates is the impact on women\u2019s reproductive rights and violence risk. This is especially salient for minoritized women. In this commentary, we describe the potential negative impact of mandates such as shelter-in-place for domestic violence victims, and how public reproductive health policy is being shaped to disadvantage women, especially minoritized women. We argue that now is the time for violence prevention leaders to advocate for bold action. This includes prioritizing the needs of women (especially minoritized women) in medical, social and legal settings using innovative intervention and service engagement (e.g., e-filing for protection orders, virtual advocacy services), urging policy makers to pass legislation to support women, and shining an accountability spotlight on leadership.", "qid": 43, "docid": "nc74h4tp", "rank": 23, "score": 11.639800071716309}, {"content": "Title: Safety and services for survivors of intimate partner violence: A researcher-practitioner dialogue on the impact of COVID-19 Content: This commentary offers a dialogue between a researcher and practitioner on the potential benefits of collaborative research to benefit survivors of intimate partner violence (IPV), a population exposed to high levels of violence and trauma. The dialogue occurred in a written, back-and-forth exchange, with the researcher and practitioner taking turns asking and responding to questions. The questions posed and answered in this commentary include: How are clients at an emergency domestic violence shelter experiencing the pandemic? How do you think a researcher or community member can help during a time like this? What should a researcher consider when engaging in collaborative research partnerships with service providers during this time? The answers offer insights into the importance of developing strong researcher-practitioner partnerships to improve services for trauma survivors during a global crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "gqhbe860", "rank": 24, "score": 11.5556001663208}, {"content": "Title: Safety and services for survivors of intimate partner violence: A researcher-practitioner dialogue on the impact of COVID-19. Content: This commentary offers a dialogue between a researcher and practitioner on the potential benefits of collaborative research to benefit survivors of intimate partner violence (IPV), a population exposed to high levels of violence and trauma. The dialogue occurred in a written, back-and-forth exchange, with the researcher and practitioner taking turns asking and responding to questions. The questions posed and answered in this commentary include: How are clients at an emergency domestic violence shelter experiencing the pandemic? How do you think a researcher or community member can help during a time like this? What should a researcher consider when engaging in collaborative research partnerships with service providers during this time? The answers offer insights into the importance of developing strong researcher-practitioner partnerships to improve services for trauma survivors during a global crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "wdv74boe", "rank": 25, "score": 11.555599212646484}, {"content": "Title: The Anxiety of Being Asian American: Hate Crimes and Negative Biases During the COVID-19 Pandemic Content: In this essay, we review how the COVID-19 (coronavirus) pandemic that began in the United States in early 2020 has elevated the risks of Asian Americans to hate crimes and Asian American businesses to vandalism. During the COVID-19 pandemic, the incidents of negative bias and microaggressions against Asian Americans have also increased. COVID-19 is directly linked to China, not just in terms of the origins of the disease, but also in the coverage of it. Because Asian Americans have historically been viewed as perpetually foreign no matter how long they have lived in the United States, we posit that it has been relatively easy for people to treat Chinese or Asian Americans as the physical embodiment of foreignness and disease. We examine the historical antecedents that link Asian Americans to infectious diseases. Finally, we contemplate the possibility that these experiences will lead to a reinvigoration of a panethnic Asian American identity and social movement.", "qid": 43, "docid": "uiezqa4p", "rank": 26, "score": 11.477899551391602}, {"content": "Title: Criminals Work from Home during Pandemics Too: a Public Health Approach to Respond to Fraud and Crimes against those 50 and above Content: This paper uses the public health framework to address the apparent impact of the coronavirus on the victimization experiences with a specific focus given to those over the age of 50. The bulk of attention is given to fraud victimization, with consideration also given to parent abuse, partner violence, and patient abuse. A review of data from the Federal Trade Commission shows that reports of most types of fraud grew significantly in the first three months of 2020 in comparison to the same time period in 2019. Differences between fraud experiences based on age are considered. Older persons lost much more to fraud than younger persons, and far more in 2020 than 2019. In addition, they reported being targeted more often for certain types of cybercrime (i.e., tech support scams). While devastating to everyone, it is concluded that the coronavirus will potentially have a more significant impact on the financial health of older persons than younger persons. It is concluded that minimizing the consequences of all forms of crimes targeting older adults will be best achieved by using a public health approach.", "qid": 43, "docid": "rx7dlpid", "rank": 27, "score": 11.201499938964844}, {"content": "Title: Socially distanced school-based nutrition program feeding under COVID 19 in the rural Niger Delta Content: Abstract The Niger Delta region of Nigeria is widely recognized as a complex and contentious space for oil exploration and production. Over the past few decades, the Niger Delta has witnessed large-scale mass peaceful mobilizations and rebellion-like conditions from violent militia groups. Oil companies have been implicated in violence perpetrated by Nigerian security forces. Local host communities have suffered greatly from corruption, political instability, violence and the environmental devastation of their farmlands and fishing grounds. Oil companies have increasingly turned to corporate social responsibility (CSR) initiatives to attempt to build or repair relations with oil-producing communities. There are also governmental and non-governmental humanitarian actors supporting various initiatives in the oil-producing areas. This article highlights the challenges that one long running micro-scale development project has faced due to the COVID 19 disease outbreak and the closure of all schools in Rivers State, Nigeria in March 2020. The school closures have halted some initiatives, but our weekly nutritional program feedings have continued in new, socially distanced forms.", "qid": 43, "docid": "j7he8x9e", "rank": 28, "score": 11.036700248718262}, {"content": "Title: Socially distanced school-based nutrition program feeding under COVID 19 in the rural Niger Delta Content: The Niger Delta region of Nigeria is widely recognized as a complex and contentious space for oil exploration and production. Over the past few decades, the Niger Delta has witnessed large-scale mass peaceful mobilizations and rebellion-like conditions from violent militia groups. Oil companies have been implicated in violence perpetrated by Nigerian security forces. Local host communities have suffered greatly from corruption, political instability, violence and the environmental devastation of their farmlands and fishing grounds. Oil companies have increasingly turned to corporate social responsibility (CSR) initiatives to attempt to build or repair relations with oil-producing communities. There are also governmental and non-governmental humanitarian actors supporting various initiatives in the oil-producing areas. This article highlights the challenges that one long running micro-scale development project has faced due to the COVID 19 disease outbreak and the closure of all schools in Rivers State, Nigeria in March 2020. The school closures have halted some initiatives, but our weekly nutritional program feedings have continued in new, socially distanced forms.", "qid": 43, "docid": "y9n9d6s3", "rank": 29, "score": 11.036699295043945}, {"content": "Title: Domestic violence and abuse, coronavirus, and the media narrative Content: Following lockdowns in countries around the world, reports emerged of a 'surge' or 'spikes' in the number of domestic violence and abuse cases It is critical to contextualise this: more men are not starting to be abusive or violent;rather, the patterns of abuse are becoming more frequent Spiking and surging make us think in terms of more one-off incidents but it is more likely that the pattern of abuse that is already there is increasing in terms of frequency and type because both parties remain together at all times Amid such a crisis, it is imperative that we continue to see the dynamics of domestic violence and abuse as both a pattern of abusive behaviours and a product of gendered social and cultural norms, rather than a reaction to a specific factor or event, such as COVID-19", "qid": 43, "docid": "haps8x4u", "rank": 30, "score": 10.926300048828125}, {"content": "Title: Initial evidence on the relationship between the coronavirus pandemic and crime in the United States Content: The COVID-19 pandemic led to substantial changes in the daily activities of millions of Americans, with many businesses and schools closed, public events cancelled and states introducing stay-at-home orders. This article used police-recorded open crime data to understand how the frequency of common types of crime changed in 16 large cities across the United States in the early months of 2020. Seasonal auto-regressive integrated moving average (SARIMA) models of crime in previous years were used to forecast the expected frequency of crime in 2020 in the absence of the pandemic. The forecasts from these models were then compared to the actual frequency of crime during the early months of the pandemic. There were no significant changes in the frequency of serious assaults in public or (contrary to the concerns of policy makers) any change to the frequency of serious assaults in residences. In some cities, there were reductions in residential burglary but little change in non-residential burglary. Thefts of motor vehicles decreased in some cities while there were diverging patterns of thefts from motor vehicles. These results are used to make suggestions for future research into the relationships between the coronavirus pandemic and different crimes.", "qid": 43, "docid": "tkqufxv8", "rank": 31, "score": 10.910200119018555}, {"content": "Title: The impact of the Covid-19 pandemic in the precipitation of intimate partner violence Content: Intimate Partner Violence (IPV) is a global pandemic and many have been victims of it long before Covid-19. International organizations have documented an increase in IPV reports during the current pandemic, raising awareness of the potential causes for such an increase. Reflecting on risk factors associated with IPV, and the underlying need of the perpetrators to exert control over the victims, it becomes increasingly important to understand how the current policies of social distancing, self-isolation, and lockdown can precipitate episodes of IPV. Furthermore, access to specialized services and health care can be compromised, and health care professionals face new challenges and demands imposed by the pandemic while managing IPV cases. This article begins by examining the main risk factors more commonly associated with IPV in the literature. It proceeds by reflecting on how these risk factors may be exacerbated during the Covid-19 pandemic, which can explain the increased number of reports. Finally, it emphasizes the new challenges faced by health care professionals, while assisting IPV victims during the pandemic and provides possible recommendations on actions to implement during and beyond the Covid-19 pandemic to prevent such cases.", "qid": 43, "docid": "0einpgeu", "rank": 32, "score": 10.82349967956543}, {"content": "Title: The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda Content: Abstract International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform \u201cessential\u201d tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "qid": 43, "docid": "lc4q55ei", "rank": 33, "score": 10.73840045928955}, {"content": "Title: The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda Content: International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform \"essential\" tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "qid": 43, "docid": "yvnjspsc", "rank": 34, "score": 10.738399505615234}, {"content": "Title: A multi-level influence model of COVID-19 themed cybercrime Content: The recent severity and frequency of cybercrime has been dominated by a single theme\u2013the COVID-19 pandemic. This research develops a multi-level influence model to explore how cybercriminals are exploiting the COVID-19 pandemic by assessing situational factors, identifying victims, impersonating trusted sources, selecting attack methods, and employing social engineering techniques. The model extends upon prior work on influence techniques and emotional appeals that cybercriminals employ, by bringing into sharper focus the role of situational factors in COVID-19 related cybercrime attacks. Content and thematic analysis was conducted on 185 distinct COVID-19 cybercrime scam incident documents, including text, images, and photos, provided by a global online fraud and cybersecurity company tracking COVID-19 related cybercrime. The analysis reveals interesting patterns about the sheer breadth and diversity of COVID-19 related cybercrime and how these crimes are continually evolving in response to changing situational factors. It is hoped that these insights and recommendations for end-users and organisations can contribute to a safer digital world as we cope with many other pressing challenges during the COVID-19 pandemic.", "qid": 43, "docid": "3nk9kvdy", "rank": 35, "score": 10.690899848937988}, {"content": "Title: The Impact of Covid-19 on Community-Based Violence Interventions Content: This paper examines the impact of Covid-19 on community-based violence interventions, especially hospital-based violence interventions and street outreach organizations. Guided by our work in Rochester, New York, we explore how the emergence of covid-19, and the subsequent social restrictions, have hampered the ability of community-based organizations to respond to violence. We also examine ways that community-based organizations can adapt to the challenges associated with Covid-19 and continue providing services to the community.", "qid": 43, "docid": "urlsn7vv", "rank": 36, "score": 10.666000366210938}, {"content": "Title: Impact of COVID-19 Lockdown Policy on Homicide, Suicide, and Motor Vehicle Deaths in Peru Content: Introduction: Although lockdown measures to stop COVID-19 have direct effects on disease transmission, their impact on violent and accidental deaths remains unknown. Our study aims to assess the early impact of COVID-19 lockdown on violent and accidental deaths in Peru. Methods: Based on data from the Peruvian National Death Information System, an interrupted time series analysis was performed to assess the immediate impact and change in the trend of COVID-19 lockdown on external causes of death including homicide, suicide, and traffic accidents. The analysis was stratified by sex and the time unit was every 15 days. Results: All forms of deaths examined presented a sudden drop after the lockdown. The biggest drop was in deaths related to traffic accidents, with a reduction of 12.66 deaths per million men per month (95% CI: -15.56, -9.76) and 3.64 deaths per million women per month (95% CI:-5.25, -2.03). Homicide and suicide presented similar level drop in women, while the homicide reduction was twice the size of the suicide reduction in men. The slope in suicide in men during the lock-down period increased by 3.62 deaths per million men per year (95% CI:0.06, 7.18). No other change in slope was detected. Conclusions: Violent and accidental deaths presented a sudden drop after the lockdown was implemented and an increase in suicide in men was observed. Falls in mobility have a natural impact on traffic accidents, however, the patterns for suicide and homicide are less intuitive and reveal important characteristics of these events, although we expect all of these changes to be transient.", "qid": 43, "docid": "chmmxehj", "rank": 37, "score": 10.566900253295898}, {"content": "Title: Special ambulatory gynecologic considerations in the era of coronavirus disease 2019 (COVID-19) and implications for future practice Content: The coronavirus disease 2019 pandemic has altered medical practice in unprecedented ways. Although much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain effects of coronavirus disease 2019 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care. In this article, we review important ambulatory gynecologic topics such as safety and mental health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible on how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns, threaten continued access to contraception and abortion services, affect prepregnancy planning, interrupt routine screening for breast and cervical cancer, increase risk of sexually transmitted infection acquisition and decrease access to treatment, and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertions can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasonography and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. Although routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papillomavirus self-samples using new cervical cancer screening guidelines that can be expanded considering the pandemic situation. Although the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to improve health equity.", "qid": 43, "docid": "mmwezwig", "rank": 38, "score": 10.543499946594238}, {"content": "Title: The Immediate Impact of COVID-19 on Law Enforcement in the United States Content: During pandemics, like COVID-19, law enforcement agencies are responsible for working with government and public health officials to contain spread, serve the local community, and maintain public order. Given the person-to-person spread of COVID-19 through respiratory droplets, law enforcement officers are also at a heightened risk of exposure due to their close contact with members of the public. To protect officers, the Centers for Disease Control and Prevention (CDC) and other agencies have made numerous recommendations for law enforcement agencies to protect officers and the public. Departments around the country have responded to the pandemic in various ways, such as reassigning personnel to high-traffic areas, suspending training, roll calls, and community outreach initiatives, only issuing citations for low-level crimes, implementing safety precautions for officers, and limiting access to department facilities. The COVID-19 pandemic also has exposed some key obstacles for law enforcement, related to communication, resource management, the enforcement of public health restrictions, and changes to crime and service patterns. Based on these early/initial responses and obstacles during the COVID-19 outbreak, the current paper highlights directions for future responses to pandemics to ensure the safety and security of police officers and the communities they serve.", "qid": 43, "docid": "mvof320m", "rank": 39, "score": 10.434499740600586}, {"content": "Title: COVID-Net: A deep learning based and interpretable predication model for the county-wise trajectories of COVID-19 in the United States Content: The confirmed cases of novel coronavirus disease (COVID-19) have been reported in the United States since late January 2020. There were over 4.8 million confirmed cases and about 320,000 deaths as of May 19, 2020 in the world. We examined the characteristics of the confirmed cases and deaths of COVID-19 in all affected counties of the United States. We proposed a COVID-Net combining the architecture of both Long Short Term Memory (LSTM) and Gated Recurrent Unit (GRU) by using the trajectories of COVID-19 during different periods until May 19, 2020, as the training data. The validation of the COVID-Net was performed by predicting the numbers of confirmed cases and deaths in subsequent 3-day, 5-day, and 7-day periods. The COVID-Net produced relatively smaller Mean Relative Errors (MREs) for the 10 counties with the most severe epidemic as of May 19, 2020. On average, MREs were 0.01 for the number of confirmed cases in all validation periods, and 0.01, 0.01, and 0.03 for the number of deaths in the 3-day, 5-day, and 7-day periods, respectively. The COVID-Net incorporated five risk factors of COVID-19 and was used to predict the trajectories of COVID-19 in Hudson County, New Jersey and New York County, New York until June 28, 2020. The risk factors include the percentage of the population with access to exercise opportunities, average daily PM2.5, population size, preventable hospitalization rate, and violent crime rate. The expected number of cumulative confirmed cases and deaths depends on the dynamics of these five risk factors.", "qid": 43, "docid": "yafo9iie", "rank": 40, "score": 10.40310001373291}, {"content": "Title: \u201cI feel like death on legs\u201d: COVID-19 isolation and mental health Content: Abstract This study investigates the personal and collective responses to COVID-19, as it is described in personal stories and newspaper reports and examines the social and economic impact of the pandemic on different societies. Although some studies have been done on the impact of COVID-19, these studies focus on epidemiology, the importance of language diversity and reflections on the pandemic. None of the studies so far have focused specifically on the impact the coronavirus has had on different societies because of the global lockdown and restrictions on people\u2019s movements. This study attempts to address this gap in the literature by focusing on how the language used in personal stories and newspaper reports reveal the impact of COVID-19 on different societies by investigating how self-isolation and lockdown measures is leading to mental health breakdown in individuals and affecting wider social and economic collapse. Prior literature (Gortner and Pennebaker, 2003) suggests that the media generally parallel society\u2019s psychological response to traumatic events making newspapers an important collective resource similar to personal stories. The scale of the pandemic is such that it has been likened to a situation of war. In this climate, where the response to the pandemic is analogous to fighting a war, it was interesting to see what effect the enforced lockdown has on people\u2019s mental health well-being and what priorities the media focus on. Smith, Anderson-Hanley, Langrock, and Compas (2005) have shown that language use in descriptions of traumatic experiences can shed insight into successful and unsuccessful coping strategies. I have therefore chosen to look at two different countries, Sri Lanka and Britain in order to investigate the following research questions: (1) Is self-isolation due to COVID-19 having an effect on mental health in Britain? And (2) What are the priorities of different countries during the crisis as evident in newspaper reports? To answer these two research questions, I have collected a small corpus of personal stories from Britain and two small corpora of newspaper reports from Britain and Sri Lanka over a span of one month. The data was analysed using corpus linguistics methodology such as keyword analysis of the two newspaper reports using AntConc (Anthony, 2019) and the personal stories were analysed using Linguistic Inquiry and Word Count (LIWC) (Pennebaker, 2015). The findings from LIWC shows that the enforced self-isolation is leading to mental health breakdown but that there are also positive emotions of the desire to help and solidarity with others. The analysis of the news reports show that Britain\u2019s priorities are centered on the government\u2019s handling of the crisis and the economy whereas Sri Lankan newspapers focus on educating people about the dangers of COVID-19.", "qid": 43, "docid": "w5u4zxdb", "rank": 41, "score": 10.334699630737305}, {"content": "Title: The effects of misleading media reports about COVID-19 on Chinese tourists\u2019 mental health: a perspective article Content: The novel coronavirus (COVID-19) has been declared apublic health emergency of international concern by the World Health Organization. This pandemic has since saturated the headlines of major international media channels that disseminate information to global citizens. However, some media coverage of COVID-19 has negatively influenced Chinese travellers\u2019 mental health due to the outbreak having been labelled \u201cChinese virus pandemonium.\u201d Key world leaders have also parroted such sensationalism; for example, President Donald Trump called COVID-19 the \u201cChinese virus\u201d. This discriminatory labelling has resulted in violent attacks on Chinese international travellers and students. This perspective article explores how misleading and discriminatory media reports may affect the mental well-being of ethnically Chinese travellers during the global COVID-19 pandemic.", "qid": 43, "docid": "7c72n11m", "rank": 42, "score": 10.2298002243042}, {"content": "Title: Terrorists and Social Media Messages: A Critical Analysis of Boko Haram\u2019s Messages and Messaging Techniques Content: Post-colonial Nigeria has been plagued with violent conflicts. A bloody civil war in which an estimated 1 million people were killed ravaged the country from 1967 to 1970. Interethnic and intra-communal conflicts have also shaken the foundations of the nation since 1960 when colonial rule ended. Other violent conflicts that have plagued the country are religious conflicts in Kano, Bauchi, Kaduna, Kafanchan, Zaria, Jos, Maiduguri, and many other places. Blood-letting in the name of religion in these and other places in Nigeria has left thousands dead and wounded. Destruction of property in the course of religious violence in Nigeria has also wreaked economic calamity on the country. For instance, wanton destruction of property during the Maitatsene religious uprising in Kano from 1980 to 1985 resulted in the loss of lives and of millions of dollars. Clashes between members of the militant Shi\u2019ite religious sect and the Nigerian army in 2016 led to the demolition of an entire neighborhood in Zaria city Nigeria\u2019s latest bout of violence emanates from a deadly terrorist group, Boko Haram. Since 2009, it has killed over 20,000 people, displaced more than one million people, and contributed to the devastation of Nigeria\u2019s northeast region. Initially, Boko Haram could not be contained by Nigerian security forces. It captured and held on to 14 local government districts and it constantly churned out online propaganda about its invisibility and its certainty that it would impose a radical Islamic government over the entire country. This chapter provides a critical analysis of Boko Haram\u2019s propaganda. It examines the group\u2019s core messages and the stylistic techniques used in delivering them. The chapter notes that Boko Haram deliberately used crude, unvanished imagery to reinforce the brutality of its actions in suicide bombings, drive-by shootings, and direct attacks against military barracks, markets, mosques, and churches. We contend that the effectiveness of Boko Haram\u2019s propaganda began to decline as it suffered military defeats by Nigerian forces.", "qid": 43, "docid": "19eawrjt", "rank": 43, "score": 10.19890022277832}, {"content": "Title: Coda: Transformative Encounters: Desiring Aliens and Hospitality in District 9 Content: This final chapter considers Neill Blomkamp\u2019s film District 9 for its commentary on human and non-human alien relationships. Returning to many of the issues raised in the previous chapters, this coda analyzes the overt biopolitical dimensions of the film and considers how desire works to challenge the violent machinations of the multinational security company, Multi-National United. It examines how the film\u2019s protagonist gets caught up in logics of exclusion in his experience of becoming-alien and approaches a position of bare life, outside the protections of the community. Ultimately, the chapter concludes the project by arguing that new, creative modes of resisting neocolonial and capitalist violence will be needed in response to biopolitical regimes, and that such creativity might arise from different desires and other modes of affect.", "qid": 43, "docid": "rnsx83hr", "rank": 44, "score": 10.194700241088867}, {"content": "Title: The German COVID-19 Survey on Mental Health: Primary Results Content: Abstract First cases of COVID-19 were reported in Wuhan, China in early December 2019. Preliminary data from China indicated a substantial impact on mental health by the pandemic and its associated lockdown measures. Such measures are unprecedented for the majority of people and may affect their lives tremendously. The current survey was developed to assess mental health in response to the lockdown in Germany. Methods We conducted a web-based self-report survey including various aspects of mental health (e.g. PHQ-D, PHQ-4, WHO-5 and comparative questions on a 5-point Likert scale concerning sleep, irritability & interpersonal violence). First wave data were taken during the height of lockdown measures in Germany from 1 April to 15 April 2020. Results A total of 3,545 volunteers took part in this cross-sectional survey. Mean age was 40.36 years (SD = 11.70; 83.1% female, 15.2% male). Acute or chronic disease was reported by 36.7% (physical) and 24.7% (mental) of subjects. Participants scored mild severity distress in the PHQ stress module. Depression and anxiety as assessed by PHQ-4 was significantly higher than in reference samples. The mean well-being score (WHO-5) was 50.7, thus pointing towards possible signs of depression. Furthermore, we found significant gender differences for anxiety and depression with women showing higher levels. 45.3% of participants reported worsened sleep, increased levels of irritation, anger and aggression compared to pre-pandemic times. Most importantly, 5% of all participants reported experiencing interpersonal violence (IPV). Discussion This is one of the first and largest surveys on mental health during the COVID-19 pandemic in a European society reflecting a relatively well educated and financially secure sample. Yet, there is evidence for a substantial mental burden with increased levels of stress, anxiety, depressive symptoms, sleep disturbance and irritability. Most importantly and also most concerning is the finding of a one-month prevalence of 5% IPV. We think it is of vital importance to continuously monitor the mental health of the general public during this pandemic and its aftermath and to carefully screen for IPV and its risk factors such as stress, sleep problems and anger.", "qid": 43, "docid": "ov0x3dho", "rank": 45, "score": 10.18970012664795}, {"content": "Title: Excess deaths hidden 100 days after the quarantine in Peru by COVID-19 Content: Objective: To make an estimate of the excess deaths caused by COVID-19 in the non-violent mortality of Peru, controlling for the effect of quarantine. Methods: Analysis of longitudinal data from the departments of Peru using official public information from the National Death Information System and the Ministry of Health of Peru. The analysis is performed between January 1, 2018 and June 23, 2020 (100 days of quarantine). The daily death rate per million inhabitants has been used. The days in which the departments were quarantined with a limit number of accumulated cases of COVID-19 were used to estimate the quarantine impact. Three limits were established for cases: less than 1, 10 and 100 cases. Result: In Peru, the daily death rate per million inhabitants decreased by -1.89 (95% CI: -2.70; -1.07) on quarantine days and without COVID-19 cases. When comparing this result with the total number of non-violent deaths, the excess deaths during the first 100 days of quarantine is 36,230. This estimate is 1.12 times the estimate with data from 2019 and 4.2 times the deaths officers by COVID-19. Conclusion: Quarantine reduced nonviolent deaths; however, they are overshadowed by the increase as a direct or indirect cause of the pandemic. Therefore, the difference between the number of current deaths and that of past years underestimates the real excess of deaths.", "qid": 43, "docid": "w57e1eu6", "rank": 46, "score": 10.17240047454834}, {"content": "Title: Analysis of the causes of moral injury in the outbreak of 2019-nCoV. Content: The infection of the novel coronavirus that originated from Wuhan, China in December 2019 converted rapidly into a pandemic by March 11, 2020. Whereas the infection mortality rate is not completely understood, it seems to be significantly beyond that of other recent pandemics (e.g., H1N1 pandemic). This paper discusses moral injury in the context of disaster and epidemic and how easily the moral psychology of individuals and society can be shaken. Moral injury is a multiscientific concept involving psychology, culture, and religion. Amid the outbreak of the novel coronavirus pneumonia, immoral behaviors and events such as violence, injury, and illness have also caused different degrees of impact on the moral standards of individuals, confusing moral cognition, destroying moral emotion, and weakening moral toughness, resulting in varying degrees of moral injury. If there is no national health, there will be no positive society for all. Based on this, the public needs to pay close attention to the moral health of the whole people and effectively avoid the occurrence of moral injury. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "2hq2seh5", "rank": 47, "score": 10.151000022888184}, {"content": "Title: Analysis of the causes of moral injury in the outbreak of 2019-nCoV Content: The infection of the novel coronavirus that originated from Wuhan, China in December 2019 converted rapidly into a pandemic by March 11, 2020. Whereas the infection mortality rate is not completely understood, it seems to be significantly beyond that of other recent pandemics (e.g., H1N1 pandemic). This paper discusses moral injury in the context of disaster and epidemic and how easily the moral psychology of individuals and society can be shaken. Moral injury is a multiscientific concept involving psychology, culture, and religion. Amid the outbreak of the novel coronavirus pneumonia, immoral behaviors and events such as violence, injury, and illness have also caused different degrees of impact on the moral standards of individuals, confusing moral cognition, destroying moral emotion, and weakening moral toughness, resulting in varying degrees of moral injury. If there is no national health, there will be no positive society for all. Based on this, the public needs to pay close attention to the moral health of the whole people and effectively avoid the occurrence of moral injury. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "i9jx8qwq", "rank": 48, "score": 10.150999069213867}, {"content": "Title: Purposeful surgical delay and the coronavirus pandemic: how will black breast cancer patients fare? Content: PURPOSE: The Coronavirus pandemic has exposed substantial racial and ethnic health and healthcare disparities. Black breast cancer patients face significant disparities in stage of presentation, surgical management, and mortality. The objective of this editorial is to examine the possible implications of the surgical delay imposed by the pandemic on black breast cancer patients. METHODS: The American College of Surgeons, the Society of Surgical Oncology, and the American Society of Breast Surgeons recommendations for surgical delay during the Coronavirus Disease 2019 (COVID-19) were evaluated and discussed. RESULTS: Guidelines by major surgical organizations on surgical delay for breast cancer patients may inadvertently exacerbate disparities in time to surgery for black breast cancer patients. Our recommendations to better characterize the impact of these guidelines on surgical delay among vulnerable populations include the following: (1) track time from biopsy-proven diagnosis to surgery by race and ethnicity, (2) document patient and institution-related reasons for surgical delay, (3) record patient and disease-related variables/reasons for the selection of breast conservation surgery, mastectomy, and reconstruction by race and ethnicity, and (4) collect data on impactful social determinants of health such as financial reserve, housing conditions, stress, and transportation. CONCLUSIONS: The COVID-19 pandemic may exacerbate delays in time to surgery among black breast cancer patients. Surgeons should incorporate collection of social determinants of health into their clinical practice to better understand the impact of COVID-19 on racial and ethnic disparities in surgical management.", "qid": 43, "docid": "bcqd56d7", "rank": 49, "score": 10.139100074768066}, {"content": "Title: Lessons Never Learned: Crisis and gender-based violence Content: The COVID-19 pandemic exposes underlying inequalities in our socio-economic and health systems, such as gender-based violence (GBV). In emergencies, particularly ones that involve quarantine, GBV often increases. Policymakers must utilize community expertise, technology and existing global guidelines to disrupt these trends in the early stages of the COVID-19 epidemic. Gender norms and roles relegating women to the realm of care work puts them on the frontlines in an epidemic, while often excluding them from developing the response. It is critical to value women's roles in society and include their voices in the decision-making process to avoid unintended consequences and ensure a comprehensive response that caters to the needs of the most vulnerable groups.", "qid": 43, "docid": "qaa2e83a", "rank": 50, "score": 10.103500366210938}, {"content": "Title: Lessons Never Learned: Crisis and gender\u2010based violence Content: The COVID\u201019 pandemic exposes underlying inequalities in our socio\u2010economic and health systems, such as gender\u2010based violence (GBV). In emergencies, particularly ones that involve quarantine, GBV often increases. Policymakers must utilize community expertise, technology and existing global guidelines to disrupt these trends in the early stages of the COVID\u201019 epidemic. Gender norms and roles relegating women to the realm of care work puts them on the frontlines in an epidemic, while often excluding them from developing the response. It is critical to value women\u2019s roles in society and include their voices in the decision\u2010making process to avoid unintended consequences and ensure a comprehensive response that caters to the needs of the most vulnerable groups.", "qid": 43, "docid": "xjt50jra", "rank": 51, "score": 10.103499412536621}, {"content": "Title: COVID-19: Threat and fear in Indonesia Content: The purpose of this article is to provide a brief report on how the Indonesian population has experienced the COVID-19 pandemic in the first 2 months since the establishment of COVID-19 Rapid Response Task Force on March 13. The discussion will focus on the psychological trauma that the population has experienced due to the lack of preparedness, the poorly equipped health care system, and lockdown policies in dealing with the spread of the coronavirus. Four different types of psychological trauma were increasingly observed, based on digital communication with people affected and reports from the news and social media. These 4 types of psychological trauma were social withdrawal, hysteria, individual violence, and collective violence. On the basis of the described psychological consequences of the pandemic, it can be assumed that both the individual and collective reactions must be considered to reduce harm of the coronavirus pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "824miiwu", "rank": 52, "score": 10.037699699401855}, {"content": "Title: COVID-19: Threat and fear in Indonesia. Content: The purpose of this article is to provide a brief report on how the Indonesian population has experienced the COVID-19 pandemic in the first 2 months since the establishment of COVID-19 Rapid Response Task Force on March 13. The discussion will focus on the psychological trauma that the population has experienced due to the lack of preparedness, the poorly equipped health care system, and lockdown policies in dealing with the spread of the coronavirus. Four different types of psychological trauma were increasingly observed, based on digital communication with people affected and reports from the news and social media. These 4 types of psychological trauma were social withdrawal, hysteria, individual violence, and collective violence. On the basis of the described psychological consequences of the pandemic, it can be assumed that both the individual and collective reactions must be considered to reduce harm of the coronavirus pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "bw80dxu7", "rank": 53, "score": 10.037698745727539}, {"content": "Title: Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology. Content: Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.", "qid": 43, "docid": "334mwg4k", "rank": 54, "score": 9.91569995880127}, {"content": "Title: Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology Content: Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.", "qid": 43, "docid": "cwceforo", "rank": 55, "score": 9.915699005126953}, {"content": "Title: COVID-19 and Intimate Partner Violence: A Call to Action. Content: The COVID-19 pandemic has escalated the risks and dangers for victims of Intimate Partner Violence (IPV). This article aims to describe the current state of IPV in Rhode Island as well as best practices for IPV screening and intervention using telehealth. We highlight the particular plight of undocumented immigrant victims of IPV and how healthcare providers can be responsive to their unique vulnerabilities and needs.", "qid": 43, "docid": "bbu44tg2", "rank": 56, "score": 9.891200065612793}, {"content": "Title: COVID-19 and Intimate Partner Violence: A Call to Action Content: The COVID-19 pandemic has escalated the risks and dangers for victims of Intimate Partner Violence (IPV) This article aims to describe the current state of IPV in Rhode Island as well as best practices for IPV screening and intervention using telehealth We highlight the particular plight of undocumented immigrant victims of IPV and how healthcare providers can be responsive to their unique vulnerabilities and needs", "qid": 43, "docid": "cfwda1sw", "rank": 57, "score": 9.891199111938477}, {"content": "Title: Crime and coronavirus: social distancing, lockdown, and the mobility elasticity of crime Content: Governments around the world restricted movement of people, using social distancing and lockdowns, to help stem the global coronavirus (COVID-19) pandemic. We examine crime effects for one UK police force area in comparison to 5-year averages. There is variation in the onset of change by crime type, some declining from the WHO \u2018global pandemic\u2019 announcement of 11 March, others later. By 1 week after the 23 March lockdown, all recorded crime had declined 41%, with variation: shoplifting (\u2212 62%), theft (\u2212 52%), domestic abuse (\u2212 45%), theft from vehicle (\u2212 43%), assault (\u2212 36%), burglary dwelling (\u2212 25%) and burglary non-dwelling (\u2212 25%). We use Google Covid-19 Community Mobility Reports to calculate the mobility elasticity of crime for four crime types, finding shoplifting and other theft inelastic but responsive to reduced retail sector mobility (MEC = 0.84, 0.71 respectively), burglary dwelling elastic to increases in residential area mobility (\u2212 1), with assault inelastic but responsive to reduced workplace mobility (0.56). We theorise that crime rate changes were primarily caused by those in mobility, suggesting a mobility theory of crime change in the pandemic. We identify implications for crime theory, policy and future research.", "qid": 43, "docid": "kzpbjvy5", "rank": 58, "score": 9.8572998046875}, {"content": "Title: Dysphagia Care Across the Continuum: A Multidisciplinary Dysphagia Research Society Taskforce Report of Service-Delivery During the COVID-19 Global Pandemic Content: At the time of writing this paper, there are over 11 million reported cases of COVID-19 worldwide. Health professionals involved in dysphagia care are impacted by the COVID-19 pandemic in their day-to-day practices. Otolaryngologists, gastroenterologists, rehabilitation specialists, and speech-language pathologists are subject to virus exposure due to their proximity to the aerodigestive tract and reliance on aerosol-generating procedures in swallow assessments and interventions. Across the globe, professional societies and specialty associations are issuing recommendations about which procedures to use, when to use them, and how to reduce the risk of COVID-19 transmission during their use. Balancing safety for self, patients, and the public while maintaining adequate evidence-based dysphagia practices has become a significant challenge. This paper provides current evidence on COVID-19 transmission during commonly used dysphagia practices and provides recommendations for protection while conducting these procedures. The paper summarizes current understanding of dysphagia in patients with COVID-19 and draws on evidence for dysphagia interventions that can be provided without in-person consults and close proximity procedures including dysphagia screening and telehealth.", "qid": 43, "docid": "2el128an", "rank": 59, "score": 9.848299980163574}, {"content": "Title: Why we march! Feminist activism in critical times: Lessons from the women's march on Washington Content: Abstract As professors, we have witnessed, anecdotally, a shift in doing social justice advocacy teaching. We have witnessed within some of our classrooms a more empowered hostility and intolerance to conversations pertaining to social justice. We agree that this phenomenon is pedagogical because this language usage not only teaches, but also legitimizes hate speech. We have witnessed the illogical extension of this hate speech with an increase in hate crimes across the country since the 2016 election, Without peaceful protest and grassroots feminist activism, we fear that this speech, this pedagogy, will spread even more violent forms of hate. This research was conducted in and around the first Women's March of 2017. We wanted to know: What were marchers' prior histories of political activism prior to the election? If this was their first time participating in such a manner, how did the election and its early political fallout inspire marchers to attend? 2) What plans did marchers have for political activism after the march? 3) What can be learned from these participants about the current state of political activism in our current era? A total of 788 individuals had taken part in the online survey. Among the participants, 45% marched on Washington, and 55% participated in the march in their local cities. We found that issues of gender equality were of great concern to many of the marchers. In particular, issues related to economic and social equity, including salary. These findings are interesting as they speak to the broader implications of gender equality. And, as the past few years have demonstrated, these issues continue to be of concern.", "qid": 43, "docid": "xmc10kv0", "rank": 60, "score": 9.831899642944336}, {"content": "Title: Singapore COVID-19 Pandemic Response as a Successful Model Framework for Low-Resource Health Care Settings in Africa? Content: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to spread and evolve across the planet. The crosscutting impacts of the virus, individual country responses to the virus, and the state of preparedness of local public health systems greatly vary across the world. The ostensibly late arrival of the virus in Africa has allowed learning, innovation, and adaptation of methods that have been successful in the early-hit countries. This article analyzes how Singapore has responded to the COVID-19 pandemic and proposes that adaptations of the Singapore pandemic response model would bode well for Africa's response to the COVID-19 pandemic in ways that also take into account regional differences in health care infrastructures, socioeconomic resilience, poverty, and the vast population diversity in the African continent. As the pandemic evolves, the lessons learned in Asia, in particular, and the emerging new experiences in African countries should inform, ideally in real time, how best to steer the world populations into safety, including those in low-resource health care settings. Finally, we note that the current COVID-19 pandemic is also a test for our collective ability to scale and surge public health in response to future and likely equally challenging zoonosis infections that jump from animals to humans, not to mention climate change-related planetary health calamities in the 21st century. Hence, what we learn effectively from the current COVID-19 pandemic shall have broad, enduring, and intergenerational relevance for the future of planetary heath and society.", "qid": 43, "docid": "2y4sjdtm", "rank": 61, "score": 9.82759952545166}, {"content": "Title: Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology Endorsed by the American College of Cardiology Content: Abstract Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.", "qid": 43, "docid": "7ciy1f6r", "rank": 62, "score": 9.822600364685059}, {"content": "Title: Mental Health and the COVID19 Pandemic. Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 43, "docid": "hze88sr4", "rank": 63, "score": 9.82040023803711}, {"content": "Title: Mental Health and the COVID19 Pandemic Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 43, "docid": "wbwd7m5w", "rank": 64, "score": 9.820399284362793}, {"content": "Title: The pandemic paradox: The consequences of COVID\u201019 on domestic violence Content: COVID-19 (the new strain of coronavirus) has been declared a global pandemic. Measures announced over recent weeks to tackle it have seen people's day-to-day life drastically altered. These changes are essential to beat coronavirus and protect health systems (UK Home Office 2020). However, there are unintended, negative consequences. As the virus continues to spread across the world, it brings with it multiple new stresses, including physical and psychological health risks, isolation and loneliness, the closure of many schools and businesses, economic vulnerability and job losses. Through all of that, children (and their mothers) are particularly vulnerable (End Violence against Children, 2020) to the risk of domestic violence. Domestic violence refers to a range of violations that happen within a domestic space. It is a broad term that encompasses intimate partner violence (IPV), a form of abuse that is perpetrated by a current or ex-partner.", "qid": 43, "docid": "1uwdekl3", "rank": 65, "score": 9.813599586486816}, {"content": "Title: Children of COVID-19: pawns, pathfinders or partners? Content: Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a \u2018new normal\u2019 that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children\u2019s interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "qid": 43, "docid": "gdz63spj", "rank": 66, "score": 9.7923002243042}, {"content": "Title: Children of COVID-19: pawns, pathfinders or partners? Content: Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a 'new normal' that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children's interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "qid": 43, "docid": "gyilcbr7", "rank": 67, "score": 9.792299270629883}, {"content": "Title: Chapter 2 Cybercrime in cloud Risks and responses in Hong Kong, Singapore Content: Abstract The popularity and commercialization of the \u201cInternetwork\u201d began in the late 1990s through the interconnection of computer networks using special gateways or routers to transfer packets of electronic data. As with many things in life, Internetwork technology has had both positive and negative effects on society, and Asia has been no exception. One of the negative effects has been a surge in Internet crime. According to a report released by the Gartner Consulting Group, in 2013 smart phone sales exceeded regular phone sales for the first time, with 968 million smart phones sold, representing 54% of the global mobile phone total and an increase of 54% from 2012. The popularity and technology of the mobile Internetwork, especially the smart mobile phone web, has changed the Internetwork landscape through the concept of cloud computing. Cloud computing is distributed computing over a network, using a program or application that can run on many connected computers and in different locations around the globe simultaneously at a reduced cost. This distributed cloud computing presents law enforcement authorities with the unique challenge of policing Internet crime. Cloud computing relies on sharing resources to achieve coherence, and in doing so creates economies of scale for converged infrastructures and shared services. Accordingly, one problem facing the authorities is the presence of trans- and multijurisdictional crimes. In this chapter, I explore this topic in the contexts of Hong Kong and Singapore, as both are key players on the international stage, especially in relation to international finance and information technology. In both locations, infrastructure works to maintain global financial center status. The remainder of this chapter is organized as follows. A brief overview of the development of cloud computing is followed by an examination of cybercrime risks in the cloud. Then, I review how the authorities in Hong Kong and Singapore respond to cybercrime risks and explore the current government policies on cloud computing, particularly in fighting cybercrime.", "qid": 43, "docid": "62cc135r", "rank": 68, "score": 9.704299926757812}, {"content": "Title: Routine activity effects of the Covid-19 pandemic on burglary in Detroit, March, 2020 Content: The spread of the coronavirus has led to containment policies in many places, with concomitant shifts in routine activities. Major declines in crime have been reported as a result. However, those declines depend on crime type and may differ by parts of a city and land uses. This paper examines burglary in Detroit, Michigan during the month of March, 2020, a period of considerable change in routine activities. We examine 879 block groups, separating those dominated by residential land use from those with more mixed land use. We divide the month into three periods: pre-containment, transition period, and post-containment. Burglaries increase in block groups with mixed land use, but not blocks dominated by residential land use. The impact of containment policies on burglary clarifies after taking land use into account.", "qid": 43, "docid": "g2mjj7my", "rank": 69, "score": 9.680899620056152}, {"content": "Title: Staying Home, Staying Safe? A Short-Term Analysis of COVID-19 on Dallas Domestic Violence Content: Abstract COVID-19 has wreaked havoc on the lives of persons around the world and social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. While designed to protect people from the coronavirus, one potential and unintended consequence of such orders could be an increase in domestic violence \u2013 including abuse of partners, elders or children. Stay-at-home orders result in perpetrators and victims being confined in close quarters for long periods of time. In this study, we use data from Dallas, Texas to examine the extent to which a local order was associated with an increase in domestic violence. Our results provide some evidence for a short-term spike in the 2 weeks after the lockdown was instituted but a decrease thereafter. We note that it is difficult to determine just how much the lockdown was the cause of this increase as the domestic violence trend was increasing prior to the order.", "qid": 43, "docid": "7o6ij2qj", "rank": 70, "score": 9.674200057983398}, {"content": "Title: Impact of COVID -19 on children: special focus on the psychosocial aspect Content: Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "qid": 43, "docid": "k30mv20e", "rank": 71, "score": 9.65880012512207}, {"content": "Title: Impact of COVID -19 on children: special focus on the psychosocial aspect. Content: Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "qid": 43, "docid": "q0ubeurh", "rank": 72, "score": 9.658799171447754}, {"content": "Title: Global oncology pharmacy response to COVID-19 pandemic: Medication access and safety Content: Response, action, and adaptation of the way health services are delivered will impact our ability to provide optimized and continuity of care while acting within resource constraints imposed by COVID-19. Care for patients with cancer is particularly important given increased infection rates and worse outcomes from COVID-19 in this patient population, as well as potential adverse outcomes if treatment pathways need to be compromised. In this commentary, we provide a global oncology pharmacy perspective (including both developed and developing nations) on how COVID-19 has impacted access to and delivery of cancer therapies. This perspective was prepared by the International Society of Oncology Pharmacy Practitioners, with input from national and regional oncology pharmacy practice groups (42 practice leaders from 28 countries and regions) who contributed to a snapshot survey between 10 and 22 April 2020. Specifically, we highlight challenges related to safe handling of hazardous drugs and maintaining high-quality medication safety standards that have impacted various stakeholders.", "qid": 43, "docid": "cc3grzjj", "rank": 73, "score": 9.609399795532227}, {"content": "Title: Global oncology pharmacy response to COVID-19 pandemic: Medication access and safety. Content: Response, action, and adaptation of the way health services are delivered will impact our ability to provide optimized and continuity of care while acting within resource constraints imposed by COVID-19. Care for patients with cancer is particularly important given increased infection rates and worse outcomes from COVID-19 in this patient population, as well as potential adverse outcomes if treatment pathways need to be compromised. In this commentary, we provide a global oncology pharmacy perspective (including both developed and developing nations) on how COVID-19 has impacted access to and delivery of cancer therapies. This perspective was prepared by the International Society of Oncology Pharmacy Practitioners, with input from national and regional oncology pharmacy practice groups (42 practice leaders from 28 countries and regions) who contributed to a snapshot survey between 10 and 22 April 2020. Specifically, we highlight challenges related to safe handling of hazardous drugs and maintaining high-quality medication safety standards that have impacted various stakeholders.", "qid": 43, "docid": "i6axnscr", "rank": 74, "score": 9.60939884185791}, {"content": "Title: Impact of Covid-19 lockdown on characteristics of autopsy cases in Greece. Comparison between 2019 and 2020 Content: In order to reduce transmission of COVID-19, social distancing measures were proposed, including spatial distancing (2m distance), or even generalized lockdown. Main concern was to prevent overwhelming of the healthcare systems, mainly of the intensive care units (ICUs) by decreasing the spreading of the disease. In Greece, the Government, after consulting with experts in the fields of infectious disease and epidemiology, implemented a rather aggressive stance with an early lockdown. Aim of our study, is to identify and compare the characteristics of cases referred for autopsy during the first month of the lockdown period for the COVID-19 outbreak, versus the cases referred during the same period in 2019. 231 autopsy cases were included in our study, 125 in 2019 and 106 in 2020. Regarding gender, age and nationality, no significant differences were detected between the two time periods. Age subgroup analysis demonstrated increased number of cases within the age group 70-79 years, in 2020. As to the place of death, the increase in the percentage of out-of-hospital deaths was not confirmed as statistically significant. Regarding type of death (violent, sudden/unexpected), the drop of violent deaths in the 2020 examined period, was not confirmed as statistically significant; however, further subgroup analysis showed a significant drop of fatal injuries resulting from road traffic accidents in the 2020 period. The slight increase of sudden/unexpected deaths, especially myocardial infarction cases, did not reach statistical significance. One month after lockdown, we cannot detect significant differences in the two time periods examined. Further study should be conducted soon when more data will become available. Frequency of fatal myocardial infarction seems to remain unaffected by the COVID-19 pandemic while deaths resulting from road traffic accidents exhibit a significant decrease. Homicides and suicides remain at low levels, in our jurisdiction area, seemingly unaffected by the COVID-19 outbreak and the subsequent lockdown. It appears that since sudden/unexpected deaths, statistically remain unaffected, the preventive measures taken by the Greek authorities prevented overwhelming of the healthcare system, which could function properly.", "qid": 43, "docid": "186nc4ue", "rank": 75, "score": 9.594200134277344}, {"content": "Title: Impact of Covid-19 Lockdown on Characteristics of Autopsy Cases in Greece. Comparison between 2019 and 2020 Content: In order to reduce transmission of COVID-19, social distancing measures were proposed, including spatial distancing (2 m distance), or even generalized lockdown. Main concern was to prevent overwhelming of the healthcare systems, mainly of the intensive care units (ICUs) by decreasing the spreading of the disease. In Greece, the Government, after consulting with experts in the fields of infectious disease and epidemiology, implemented a rather aggressive stance with an early lockdown. Aim of our study, is to identify and compare the characteristics of cases referred for autopsy during the first month of the lockdown period for the COVID-19 outbreak, versus the cases referred during the same period in 2019. 231 autopsy cases were included in our study, 125 in 2019 and 106 in 2020. Regarding gender, age and nationality, no significant differences were detected between the two time periods. Age subgroup analysis demonstrated increased number of cases within the age group 70-79 years, in 2020. As to the place of death, the increase in the percentage of out-of-hospital deaths was not confirmed as statistically significant. Regarding type of death (violent, sudden/unexpected), the drop of violent deaths in the 2020 examined period, was not confirmed as statistically significant; however, further subgroup analysis showed a significant drop of fatal injuries resulting from road traffic accidents in the 2020 period. The slight increase of sudden/unexpected deaths, especially myocardial infarction cases, did not reach statistical significance. One month after lockdown, we cannot detect significant differences in the two time periods examined. Further study should be conducted soon when more data will become available. Frequency of fatal myocardial infarction seems to remain unaffected by the COVID-19 pandemic while deaths resulting from road traffic accidents exhibit a significant decrease. Homicides and suicides remain at low levels, in our jurisdiction area, seemingly unaffected by the COVID-19 outbreak and the subsequent lockdown. It appears that since sudden/unexpected deaths, statistically remain unaffected, the preventive measures taken by the Greek authorities prevented overwhelming of the healthcare system, which could function properly.", "qid": 43, "docid": "7gw6a6nv", "rank": 76, "score": 9.594199180603027}, {"content": "Title: COVID-19, domestic violence and abuse, and urgent dental and oral and maxillofacial surgery care Content: Household isolation measures to reduce coronavirus transmission during the COVID-19 pandemic have resulted in increased risk of domestic violence and abuse (DVA). DVA physical injury most frequently involves the face. Dentists, dental care professionals, oral surgeons and oral and maxillofacial surgeons all have a critical part to play in identifying patients experiencing DVA, who present with dental and facial injury, and in making referrals to specialist agencies. This paper describes how to ask questions about DVA sensitively and how to make an appropriate referral. Early intervention and referral to a DVA advocate can prevent an abusive situation becoming worse with more intense violence. It can save lives.", "qid": 43, "docid": "cf26y8t6", "rank": 77, "score": 9.573399543762207}, {"content": "Title: Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America Content: BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a \u201cstay-at-home\u201d order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.", "qid": 43, "docid": "2pfeogz0", "rank": 78, "score": 9.521900177001953}, {"content": "Title: Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America Content: BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a \"stay-at-home\" order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.", "qid": 43, "docid": "sdrst5nm", "rank": 79, "score": 9.521899223327637}, {"content": "Title: Letter to the editor in response to: COVID-19 pandemic and challenges for socio-economic issues, healthcare and national programs in India (Gopalan and Misra) Content: Article by Gopalan and Misra is very informative and covers the current challenges arising due to COVID-19. Further, authors has attempted to explore the various socioeconomic and medical aspects affected during this COVID-19 pandemic. It starts with the economic issues, social impacts, cultural influences, and the health related national programs which are regularly getting impacted owing to the ongoing epidemic. The paper throws light on how the pandemic has strongly affected the jobs, businesses transportation, travel, and other sectors which ultimately influence the social-economic balance of the society. This has further led to the decrease in the GDP of the country. The daily wagers and the local business personnel are the most affected ones during this period.", "qid": 43, "docid": "380sajt9", "rank": 80, "score": 9.512200355529785}, {"content": "Title: The Impact of the COVID-19 Pandemic on Bariatric Surgery: Results from a Worldwide Survey Content: BACKGROUND: The ongoing \"coronavirus disease 19\" (COVID-19) pandemic has had a strong effect on the delivery of surgical care worldwide. Elective surgeries have been canceled or delayed in order to reallocate resources to the treatment of COVID-19 patients. Currently, the impact of the COVID-19 pandemic on bariatric and metabolic surgical practice remains unclear. METHODS: An internet-based online survey was performed among bariatric surgeons worldwide. The survey was sent to bariatric surgeons via the International Bariatric Club Facebook group and by electronic mail via the International Federation for the Surgery of Obesity and metabolic disorders (IFSO) secretariat to members of the associated national IFSO societies. RESULTS: One hundred sixty-nine (n = 169) bariatric surgeons participated in the survey. The majority of the respondents postponed preoperative upper gastrointestinal tract endoscopies, appointments in the outpatient clinic and bariatric operations. Most surgeons performed video calls for follow-up appointments instead of meeting the patients in the outpatient clinics. Laparoscopy was still the preferred treatment for surgical emergencies, but a trend towards conservative treatment of acute appendicitis and acute cholecystitis was shown. Rapid preoperative COVID-19 testing availability was poor; therefore, routine screening of emergency bariatric cases was not widely provided. A wide variance occurred regarding precautions and personal protection equipment among the participants. CONCLUSION: The COVID-19 pandemic showed a strong impact on bariatric surgical practice regarding surgical and outpatient planning as well as personnel management. Coordinated effort from the national bariatric societies should focus on strict implementation of the current recommendations regarding precaution measures and personal protection equipment. Further studies should evaluate how this impact will evolve in the near future.", "qid": 43, "docid": "2ozl0v9l", "rank": 81, "score": 9.502900123596191}, {"content": "Title: The Impact of the COVID-19 Pandemic on Bariatric Surgery: Results from a Worldwide Survey Content: BACKGROUND: The ongoing \u201ccoronavirus disease 19\u201d (COVID-19) pandemic has had a strong effect on the delivery of surgical care worldwide. Elective surgeries have been canceled or delayed in order to reallocate resources to the treatment of COVID-19 patients. Currently, the impact of the COVID-19 pandemic on bariatric and metabolic surgical practice remains unclear. METHODS: An internet-based online survey was performed among bariatric surgeons worldwide. The survey was sent to bariatric surgeons via the International Bariatric Club Facebook group and by electronic mail via the International Federation for the Surgery of Obesity and metabolic disorders (IFSO) secretariat to members of the associated national IFSO societies. RESULTS: One hundred sixty-nine (n = 169) bariatric surgeons participated in the survey. The majority of the respondents postponed preoperative upper gastrointestinal tract endoscopies, appointments in the outpatient clinic and bariatric operations. Most surgeons performed video calls for follow-up appointments instead of meeting the patients in the outpatient clinics. Laparoscopy was still the preferred treatment for surgical emergencies, but a trend towards conservative treatment of acute appendicitis and acute cholecystitis was shown. Rapid preoperative COVID-19 testing availability was poor; therefore, routine screening of emergency bariatric cases was not widely provided. A wide variance occurred regarding precautions and personal protection equipment among the participants. CONCLUSION: The COVID-19 pandemic showed a strong impact on bariatric surgical practice regarding surgical and outpatient planning as well as personnel management. Coordinated effort from the national bariatric societies should focus on strict implementation of the current recommendations regarding precaution measures and personal protection equipment. Further studies should evaluate how this impact will evolve in the near future.", "qid": 43, "docid": "l2f96uvv", "rank": 82, "score": 9.502899169921875}, {"content": "Title: The Conundrums of Counselling Women in Violent Intimate Partner Relationships in South Africa: Implications for Practice Content: Little research focuses on how counsellors experience counselling encounters concerning intimate partner violence. This study reports on narrative research conducted with eight South African non-governmental organisation counsellors. Participants spoke of creating productive and caring counselling dynamics, and providing non-directive counselling. However, they also indicated providing moral guidance, particularly in cases where pregnancy or children were involved. Success was viewed rather narrowly as the women leaving the relationship, setting up \u2018all-or-nothing\u2019 outcomes. Such \u2018success\u2019 led to counsellor happiness, whilst failure in this regard led to counsellors experiencing anger and burn-out. We conclude that the conundrums evident in these data are grounded in patriarchal systems, limiting the efficacy of counselling based on a bondage and deliverance narrative. Implications for practice and training are also outlined.", "qid": 43, "docid": "eahx37cy", "rank": 83, "score": 9.498600006103516}, {"content": "Title: Staying safe during COVID-19: How a pandemic can escalate risk for intimate partner violence and what can be done to provide individuals with resources and support Content: The emergence of COVID-19 presents unprecedented challenges in keeping individuals experiencing intimate partner violence (IPV) safe in the United States and abroad. This commentary explores how COVID-19 may be increasing risk for IPV and what strategies may be used presently, and in the future, to mitigate IPV risk during crises. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "vpptmanx", "rank": 84, "score": 9.49470043182373}, {"content": "Title: Staying safe during COVID-19: How a pandemic can escalate risk for intimate partner violence and what can be done to provide individuals with resources and support. Content: The emergence of COVID-19 presents unprecedented challenges in keeping individuals experiencing intimate partner violence (IPV) safe in the United States and abroad. This commentary explores how COVID-19 may be increasing risk for IPV and what strategies may be used presently, and in the future, to mitigate IPV risk during crises. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "zbv1ilyx", "rank": 85, "score": 9.494699478149414}, {"content": "Title: Intimate partner violence crisis in the COVID-19 pandemic: how can radiologists make a difference? Content: \u2022 The COVID-19 crisis resulted in a variety of physical and mental health issues beyond the viral infection itself, as indicated by an increase in domestic violence. \u2022 Radiologists should be aware of typical intimate partner violence (IPV) injury patterns, actively ask potential IPV victims about the cause of injury, and be familiar with support systems for IPV victims of their institutions. \u2022 Emergency and radiology departments should review their protocols for identifying and supporting IPV victims, and train their staff to work together to implement these measures during and beyond the COVID-19 crisis.", "qid": 43, "docid": "0gaipzlh", "rank": 86, "score": 9.441200256347656}, {"content": "Title: COVID-19 as a Frying Pan: The Promise and Perils of Pandemic-Driven Reform. Content: : The imposition of new regulations can send industries scrambling to comply, fostering innovation in doing so. In the case of the COVID-19 pandemic, it is deregulation that has yielded sudden changes in how we police and treat people with opioid use disorder (OUD). Arbitrary laws and counterproductive policies previously subject to only incremental reform have given way to sweeping changes: people convicted of nonviolent drug crimes have been released from jails and prisons, the enforcement of drug laws has been cast aside as a priority, and the regulations surrounding addiction treatment medications and treating patients with OUD have been greatly loosened. These are changes many practitioners and advocates have sought for years if not decades, but they come with the reality that the old systems are culturally entrenched and likely to be resilient. It is critical that researchers evaluate these changes and synthesize the results with existing evidence in ways that empower efforts to make the most effective responses permanent. The COVID-19 pandemic makes for a challenging research environment, but its OUD-related interventions have created new regulatory systems that lend themselves to valuable opportunities for evaluation as natural experiments by the burgeoning field of legal epidemiology.", "qid": 43, "docid": "pg5ts74v", "rank": 87, "score": 9.371800422668457}, {"content": "Title: COVID-19 as a Frying Pan: The Promise and Perils of Pandemic-Driven Reform Content: : The imposition of new regulations can send industries scrambling to comply, fostering innovation in doing so. In the case of the COVID-19 pandemic, it is deregulation that has yielded sudden changes in how we police and treat people with opioid use disorder (OUD). Arbitrary laws and counterproductive policies previously subject to only incremental reform have given way to sweeping changes: people convicted of nonviolent drug crimes have been released from jails and prisons, the enforcement of drug laws has been cast aside as a priority, and the regulations surrounding addiction treatment medications and treating patients with OUD have been greatly loosened. These are changes many practitioners and advocates have sought for years if not decades, but they come with the reality that the old systems are culturally entrenched and likely to be resilient. It is critical that researchers evaluate these changes and synthesize the results with existing evidence in ways that empower efforts to make the most effective responses permanent. The COVID-19 pandemic makes for a challenging research environment, but its OUD-related interventions have created new regulatory systems that lend themselves to valuable opportunities for evaluation as natural experiments by the burgeoning field of legal epidemiology.", "qid": 43, "docid": "sx8d9j72", "rank": 88, "score": 9.37179946899414}, {"content": "Title: An increasing risk of family violence during the Covid-19 pandemic: Strengthening community collaborations to save lives Content: Abstract Though necessary to slow the spread of the novel Coronavirus (Covid-19), actions such as social-distancing, sheltering in-place, restricted travel, and closures of key community foundations are likely to dramatically increase the risk for family violence around the globe. In fact many countries are already indicating a dramatic increase in reported cases of domestic violence. While no clear precedent for the current crisis exists in academic literature, exploring the impact of natural disasters on family violence reports may provide important insight for family violence victim-serving professionals. Improving collaborations between human welfare and animal welfare agencies, expanding community partnerships, and informing the public of the great importance of reporting any concerns of abuse are all critical at this time.", "qid": 43, "docid": "v9fdn4uu", "rank": 89, "score": 9.340999603271484}, {"content": "Title: Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement from the Cardiac Society of Australia and New Zealand (CSANZ) # Content: Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. Challenges The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. Recommendations Every effort should be made to deliver safe ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.", "qid": 43, "docid": "bc7q8swu", "rank": 90, "score": 9.304100036621094}, {"content": "Title: Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement from the Cardiac Society of Australia and New Zealand (CSANZ) Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. CHALLENGES: The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. RECOMMENDATIONS: Every effort should be made to deliver safe, ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.", "qid": 43, "docid": "vxw4dvnb", "rank": 91, "score": 9.304099082946777}, {"content": "Title: Post COVID-19 ecological and social reset: moving away from capitalist growth models towards tourism as Buen Vivir Content: Tourism has been one of the industries most highly affected by COVID-19. The COVID-19 global pandemic is an \u2018unprecedented crisis\u2019 and has exposed the pitfalls of a hyper consumption model of economic growth and development. The scale of immediate economic impacts of the COVID-19 pandemic has shattered the myth of \u2018catch up development\u2019 and \u2018perpetual growth\u2019. The Crisis has brought unintended degrowth, presenting opportunities for an economic and social \u2018reset\u2019. In terms of long-term thinking post COVID-19, it is time to change the parameters of how we imagine a trajectory going forward, to prefigure possibilities for contesting capitalist imperatives that \u2018there is no alternative\u2019. In relation to tourism, the pandemic provides an opportunity for reimaging tourism otherwise, away from exploitative models that disregard people, places, and the natural environment, and towards a tourism that has positive impacts. Non-western alternatives to neo-colonial and neoliberal capitalism, such the South American concept of \u2018Buen Vivir\u2019, can help us to shift priorities away from economic growth, towards greater social and environmental wellbeing, and meaningful human connections. Taking a Buen Vivir approach to tourism will continue the degrowth momentum, for transformative change in society within the earth\u2019s physical limits. Yet Buen Vivir also redefines the parameters of how we understand \u2018limits\u2019. In limiting unsustainable practices in development and tourism, a focus on Buen Vivir actually creates growth in other areas, such as social and environmental wellbeing, and meaningful human connection. Buen Vivir can reorient the tourism industry towards localised tourism, and slow tourism because the principles of Buen Vivir require these alternatives to be small-scale, local and benefiting host communities as well as tourists to increase the wellbeing for all.", "qid": 43, "docid": "iflnrp22", "rank": 92, "score": 9.299099922180176}, {"content": "Title: The effect of COVID-19 pandemic on the Turkish society Content: Pandemics leave significant marks on the memories of societies with their permanent impacts. Going beyond a cause of disease or death, they can have consequences in many aspects, psychological, social and economic ones being in the first place. The Covid-19 outbreak, which first emerged in China and has spread to the whole world as of the first months of 2020, has the potential to constitute a breaking the course of history, as well. Turkey is located on the transit point between Asia and Europe with its geographical position, and thus, received its share from the outbreak of Covid-19, which spreads through social contact. The first official case was recorded on 11 March 2020, and then the virus spread rapidly. This study aims to assess the attitude of the public towards Covid-19 at times when the impact of the disease reached maximum. To this end, data were collected from 1586 people with different socio-demographic features through Covid-19 Pandemic Community Scale. The impact of the pandemic on the society was measured in three dimensions as Sensitivity to Pandemic, Protection against Pandemic and Social Trust. The research results showed that the people had high levels of sensitivity to the pandemic, exerted the maximum effort for protection and social trust was above the average although it fell behind the other dimensions. As a consequence, it can be concluded that Covid-19 has had a significant impact on the Turkish people.", "qid": 43, "docid": "98dztptq", "rank": 93, "score": 9.248800277709961}, {"content": "Title: Domestic violence amid COVID-19. Content: This manuscript highlights the risk that shelter-in-place instructions during COVID-19 places on victims of domestic violence and serves as a call-to-action to address this crisis. In the midst of the COVID-19 pandemic, \"stay at home\" has become the mantra of governments and public health organizations alike. But for victims of domestic violence, home is often not a place of safety. Staying at home not only places survivors of domestic violence at risk for further violence, but also isolates them from networks of support. Containment policies may lead to higher rates of domestic violence, substance abuse, anxiety, major depression, suicide, and other manifestations of unmet mental health needs. Job losses and financial insecurity may tip at-risk relationships into violence.", "qid": 43, "docid": "er50rvxw", "rank": 94, "score": 9.190600395202637}, {"content": "Title: Debate: COVID\u201019 and children in India Content: The COVID\u201019 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world\u2019s children amidst the pandemic which may have lasting consequences. The COVID\u201019 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children\u2019s lives \u2013 their health, development, learning, behaviour and their families\u2019 economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 43, "docid": "8bu6xadf", "rank": 95, "score": 9.17650032043457}, {"content": "Title: Debate: COVID-19 and children in India Content: The COVID-19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world's children amidst the pandemic which may have lasting consequences. The COVID-19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children's lives - their health, development, learning, behaviour and their families' economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 43, "docid": "swgb2tzx", "rank": 96, "score": 9.176499366760254}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) and Neurosurgery: Literature and Neurosurgical Societies Recommendations Update Content: BACKGROUND: Since January 2020, when the pathogen causing the coronavirus disease was identified in humans, the literature on coronavirus disease 2019 (COVID-19) has grown exponentially to more than 4000 publications. There is the need to provide an update for each single medical discipline, including neurosurgery, to be used by single professionals or to be distributed through the neurosurgical community and to be used by governments in designing new scenario of care. METHODS: A review of the MEDLINE database was performed on April 13, 2020. Search terms included \"COVID-19,\" \"neurosurgery,\" and \"surgery.\" A review of documents published on the webpage of the WFNS (World Federation of Neurosurgical Societies) and of the 5 continental associations of neurosurgical societies, AANS (American Association of Neurological Surgeons), AASNS (Asian Australasian Society of Neurological Surgeons), CAANS (Continental Association of African Neurosurgical Societies), EANS (European Association of Neurosurgical Societies), and FLANC (Latin American Federation of Neurosurgical Societies), representing the 119 national neurosurgical societies around the world, was performed. RESULTS: The literature search yielded 38 results that were manually reviewed. Fourteen manuscripts were considered eligible. They described suggestions and considerations to optimize care of neurosurgical patients, editorials on operational models, perspectives from neurosurgical departments, letters to the editor describing experiences on how to help medical staff to be prepared in advance for pandemic situations, and descriptions of regional or departmental models and/or organizational schemes. The webpages of the searched societies reported a total of 57 documents. CONCLUSIONS: The neurosurgical scientific community has promptly reacted to the COVID-19 outbreak by producing a growing number of documents that could serve as guidance for neurosurgeons all over the world. Neurosurgical societies will represent the key institutions for guiding the neurosurgical community to overcome the COVID-19 crisis.", "qid": 43, "docid": "5234vpfi", "rank": 97, "score": 9.163100242614746}, {"content": "Title: Geographies of Covid-19: how space and virus shape each other Content: This paper contributes to a geographically-informed preliminary assessment of the diverse and uneven immediate impacts of the Covid-19 pandemic, and outlines an agenda for geographical studies of its longer term effects. Intrigued by the apparent tendency of an inverse relationship between a country\u2019s health security capacities and Covid-19 mortalities, the paper explores the significance of a range of geographically situated contextual factors in the realms of the economy, governance and culture as mediators of the public health impacts of Covid-19, and questions how these realms may also be reshaped by this viral pandemic. The paper concludes with reflections on the path dependency and state centrality of pandemic response, and the potential post-pandemic reconfiguration of state-market-society relationships.", "qid": 43, "docid": "7hqai3wj", "rank": 98, "score": 9.160400390625}, {"content": "Title: Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data Content: BACKGROUND. The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS. We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS. The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS. The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.", "qid": 43, "docid": "lbrpbhpg", "rank": 99, "score": 9.138699531555176}, {"content": "Title: Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data Content: BACKGROUND: The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS: We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.", "qid": 43, "docid": "p077nn3o", "rank": 100, "score": 9.13869857788086}]}